http://131.113.63.82/api.php?action=feedcontributions&user=Noriko.hiroi&feedformat=atomJapanese society for quantitative biology - User contributions [en]2024-03-29T10:32:05ZUser contributionsMediaWiki 1.35.4http://131.113.63.82/index.php?title=English&diff=248233English2023-01-10T06:39:21Z<p>Noriko.hiroi: /* Core members */</p>
<hr />
<div><span style="color: red">news!(19/10/2015)</span><br />
<br/><br />
We will hold<br/><br />
<span style="color: green">'''''NIG International Symposium 2016 + ROIS Event''''' <br><br />
and '''''Toyoda Physical & Chemical Research Institute Workshop''''' </span><br />
<br/>on Jan 8th ~ 13th, 2016.<br />
='''Japan q-bio week''' (Jan/8/2016~Jan/13/2016)=<br />
We have a series of international symposiums and workshops (Japan q-bio week) 8/Jan/2016 to 13/2016 instead of the annual meeting of the Japanese Society for Quantitative Biology. Most of them will be held as NIG International Symposium 2016. All these symposiums and workshops are organized by the core-members of Japanese Society for Quantitative Biology.<br />
<!-- This year's annual meeting of the Japanese Society for Quantitative Biology will be held as NIG International Symposium 2015, titled [[NIG_International_Symposium_2015_JapanQ-Bioweek|NIG INternational Symposium 2015: Japan Q-Bio week – force, information, and dynamics]] on Jan 7th to 11th, 2016 at Institute of Industrial Science, the University of Tokyo, and Jan 12th and 13th, 2016 at National Institute of Genetics. --><br />
<br />
*'''Tokyo Workshops'''<br />
** Date: Jan/8/2016<br />
** Site:Institute of Industrial Science, <span style="color: red"> Bld. S </span>, the Univ. Tokyo, Komaba<br />
***[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop (9:00 - 12:00)] '''Bridging Theory & Experiment'''<br />
***[http://symposium.crmind.net/EIC2015/Home.html Toyoda Physical & Chemical Research Institute Workshop (13:00 - 18:00)] '''Entropy, Information & Control'''<br><br />
<br />
*'''[[IIS_Sympo|NIG International Symposium - Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]]'''<br />
** Date:Jan/9/2016~Jan/11/2016<br />
** Site:Institute of Industrial Science, <span style="color: red">Bld. An</span>, the Univ Tokyo Komaba<br />
* '''[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html ROIS Event - Mishima Symposium:Quantitative Biology - force, information and dynamics]'''<br />
** Date:Jan/12/2016~Jan/13/2016<br />
** Site:National Institute of Genetics<br />
<br />
<br />
== What is the Japanese Society for Quantitative Biology <br>(Q-BioJP)? ==<br />
The '''Japanese Society for Quantitative Biology''' ('''Q-BioJP''') is a non-profit organization founded in 2008 that is dedicated to the advancement of the field of quantitative biology.<br><br />
The mission of the '''Q-BioJP''' is to<br />
* bring together the various fields of biological research that will benefit from quantitative analysis<br />
* provide an interdisciplinary forum for research, and to provide opportunities for collaboration in quantitative biology<br />
* promote the field of quantitative biology and to advance our understanding of biological systems.<br />
[[Main_Page|Japanese "Main Page"]]<br />
<br><br />
<br />
== Background of the foundation ==<br />
'''A PERIOD OF TRANSITION'''<br><br />
Biology is in a period of transition, from being a mostly descriptive and qualitative discipline towards being more analytical and quantitative. It is hoped that this change in emphasis will produce insights, and also new technologies. These approaches will be carried out by a new kind of biologist who can deal with the requirements of this new field.<br><br />
'''A FUTURE GOAL OF BIOLOGY'''<br><br />
While most of modern biology was focused on the properties of individual molecules, a future goal will be to understand their dynamics, and will require finding new ways of thinking and analysing these processes at a level beyond the individual components and their static properties. For solutions to these comprehensive questions, biology is now looking to other disciplines. Systems Biology has built strong links between Biology, Computer Sciences, and Mathematics to develop integrated approaches to deal with recent explosive increase in biological knowledge.<br><br />
'''HOW TO APPROACH THE PRINCIPLES'''<br><br />
Now to approach the principles that underlie their dynamical behaviors, the Physical and Chemical Sciences may provide a useful precedent. We also notice biological systems may have design principles that can be understood from an Engineering point of view.<br><br />
[[About_us|Japanese "About us"]]<br />
<br><br />
<br />
== The Aim of the Q-BioJP ==<br />
'''TO PROMOTE SPONTANEOUS ACTION'''<br><br />
Our purpose is to promote spontaneous action of each scientist for the development of quantitative biology.<br><br />
'''TO ESTABLISH AN INTERDISCIPLINARY ENVIRONMENT'''<br><br />
To achieve this objective we plan to establish an interdisciplinary research environment; such an environment will accelerate the natural convergence of different but related fields, and the expansion research into at the interface of different areas of research.<br><br />
The interactions fostered by us will transcend the boundaries between Biology and Physics, Chemistry, Engineering, Mathematics and Computational sciences.<br><br />
'''TO FORM A COMMUNITY FOR DEVELOPMENTS OF THE FIELD'''<br><br />
Above all, we aim to form a community that will be nourished by, and contribute to, the new developments which arise from the interdisciplinary research environment, and will provide the means for people with different approaches to related problems to come together and find novel and interesting solutions.<br><br />
[[About_us|Japanese "About us"]]<br />
<br><br />
<br />
== Targeting Subject ==<br />
We explore techniques and methods to quantify the physical properties that determine the dynamics of biological phenomena. Our main focus is on '''cellular-level biology''', but we are also concerned with the structure and organization of cells. The behavior of cells is influenced by events at '''a molecular level''' and upwards to '''the tissue and organism level'''. A new-generation model of Q-BioJP can take initiatives at '''medical sciences''' such as pharmacokinetics and cancer research. Q-BioJP will strive to understand the various levels of biological systems and the relationships that exist between them.<br><br />
[[About_us|Japanese "About us"]]<br />
<br><br />
<br />
== Agenda ==<br />
To these ends, we operate the following three strategies:<br />
====1. An annual meeting to - foster excellence in research and education -====<br />
We organize an annual scientific meeting which consists of technical tutorials and sessions focused on selected topics.<br><br />
* '''target audience''': Scientists that have already begun a research in the field of quantitative biology or have concrete plans to start.<br />
* '''objective''': The meeting provides a program for the interdisciplinary community of quantitative biologists to promote sharing of information to solve technical problems in their research, and to promote discussions of our future direction.<br />
<span style="color: green">The 5th Annual Meeting will be held on 23rd - 25th November 2012 at the Convention Hall in Institute of Industrial Science, the University of Tokyo. </span><br />
<br><br />
[[5th_Annual_Meeting|5th Annual Meeting]]<br><br />
[[Events|Japanese Events]]<br />
<br />
====2. Caravan - scholarly dissemination of research -====<br />
* '''target audience''': researchers who are interested in quantitative biology but require guidance in starting a research program in this area “quantitative biology”.<br />
* '''objective''': To showcase exciting examples of quantitative biology with an emphasis on the importance of the quantitative point of view in biology.<br />
<br />
====3. Mailing list====<br />
* '''objective''' : exchanging information on topics relating to quantitative biology.<br />
* '''members in the list''': '''There is no condition to participate our mailing list except your motivation'''. You can join anytime via a direct invitation by a core member. (<span style="color: green">This mailing list is basically managed in Japanese.</span>)<br />
<br><br />
<br />
===All are welcome who would strive together to ensure the future of this new basic scientific field!===<br />
<br><br />
<br><br />
==== Links in English on q-bio.jp ====<br />
*[http://www.iis.u-tokyo.ac.jp/What_e/What_e.html Institute of Industrial Science, the University of Tokyo][[Events|in "Events"]]<br />
*[http://www.med.osaka-u.ac.jp/index-e.html Graduate School of Medicine/Faculty of Medicine, Osaka University][[Events|in "Events"]]<br />
*[http://www.nig.ac.jp/index-e.html National Institute of Genetics][[Events|in "Events"]]<br />
*[http://www.jsbi.org/en Japanese Society for Bioinformatics][[Events|in "Events"]]<br />
*[http://www.springer.com/physics/book/978-3-540-40824-6 Synergetics by Hermann Haken][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.elsevierdirect.com/ISBN/9780123497031/Differential-Equations-Dynamical-Systems-and-an-Introduction-to-Chaos| Differential Equations Dynamical Systems and an Introduction to Chaos by Dr. Morris W. Hirsch, Dr. Stephen Smale and Dr. Robert Devaney][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.perseusbooks.com/perseus/book_detail.jsp?isbn=0738204536 Nonlinear Dynamics And Chaos With Applications To Physics, Biology, Chemistry, And Engineering by Steven H. Strogatz][[Documents|in "Documents", recommedned text books]]<br />
*[http://press.princeton.edu/titles/112.html Random Walks in Biology by Howard C. Berg][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.cambridge.org/us/catalogue/catalogue.asp?isbn=0521783372 Biological Physics of the Developing Embryo by Gabor Forgacs and Stuart A. Newman][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.springer.com/mathematics/mathematical+biology/book/978-0-387-75846-6 Mathematical Physiology by James Keener, James Sneyd][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.garlandscience.com/textbooks/0815341636.asp Physical Biology of the Cell by Rob Phillips, Jane Kondev, Julie Theriot][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.weizmann.ac.il/mcb/UriAlon/bookUri.html An Introduction to Systems Biology - Design Principles of Biological Circuits by Uri Alon][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.micro-manager.org/| micromanager][[Documents|in "Documents", image processing tools]]<br />
*[http://www.mathworks.com/products/image/demos.html MathWorks Image Proecssing Toolbox][[Documents|in "Documents", image processing tools]]<br />
*[http://homepages.inf.ed.ac.uk/rbf/HIPR2 image processing learning resources][[Documents|in "Documents", image processing tools]]<br />
*[http://q-bio.jp/wiki/News#Biology.2FGenetics.2FEvolution_Postdoctoral_Fellow_Position.2C__Fred_Hutchinson_Cancer_Research_Center_.28091006.29_New.21.21 Biology/Genetics/Evolution Postdoctoral Fellow Position, Fred Hutchinson Cancer Research Center (091006)][[News|in "News", Job opportunity]]<br />
<br />
==Core members==<br />
*'''Kazuhiro Aoki''' (Kyoto University)<br />
*'''Yukinobu Arata''' (RIKEN, Advanced Science Institute)<br />
*'''Hiroshi Ito''' (Kyushu University)<br />
*'''Seiichi Uchida''' (Kyushu University)<br />
*'''Hiromasa Oku''' (Gunma University)<br />
*'''Akatsuki Kimura''' (Cell Architecture Laboratory, National Institute of Genetics)<br />
*'''Katsuyuki Kunida''' (Fujita Health University)<br />
*'''Tetsuya J. Kobayashi''' (Institute of Industrial Science, the University of Tokyo)<br />
*'''Kaoru Sugimura''' (Graduate School of Science, the University of Tokyo)<br />
*'''Takao K Suzuki''' (Graduate School of Frontier Sciences, the University of Tokyo)<br />
*'''Madoka Suzuki''' (Osaka University)<br />
*'''Hiroaki Takagi''' (Department of Physics, School of Medicine, Nara Medical University)<br />
*'''Jun-nosuke Teramae''' (Kyoto University)<br />
*'''Yuki Tsukada''' (Division of Biological Science, Graduate School of Science, Nagoya University)<br />
*'''Itoshi Nikaido''' (RIKEN)<br />
*'''Shigenori Nonaka''' (NIBB)<br />
*'''Kayo Hibino'''(National Institute of Genetics)<br />
*'''Tsuyoshi Hirashima''' (MBI)<br />
*'''Noriko Hiroi''' (KAIT & Keio University School of Medicine)<br />
*'''Akira Funahashi''' (Department of Biosciences and Informatics, Keio University)<br />
*'''Yusuke T. Maeda''' (Kyushu University)<br />
*'''Takashi Murata''' (KAIT)<br />
<br><br />
<br><br />
tentatively away:<br><br />
*'''Rinshi S. Kasai''' (Institute for Integrated Cell-Material Sciences,Kyoto University)<br />
*'''Shuji Ishihara''' (Meiji University)<br />
*'''Kazuhisa Kinoshita''' (RIKEN Advanced Science Institute)<br />
*'''Hiroshi Kimura''' (Department of Mechanical Engineering, Tokai University)<br />
*'''Satoshi Sawai''' (Graduate School of Arts and Sciences, University of Tokyo)<br />
*'''Hidekazu Tsutsui''' (JAIST)<br />
*'''Takahiro Harada'''<br />
*'''Yutaka Matsubayashi''' (Bournemouth University)<br />
<br />
== Acknowledgement ==<br />
We are grateful to Dr. Aitor Gonza ́ lez (Institute for Virus Research, Kyoto University, Japan) , Dr. Jonathan James Ward (Cellular architecture Group, Cell Biology and Biophysics Unit, EMBL-Heidelberg, Germany), Kris Popendorf (Bioinformatics Laboratory, Department of Bioscience and Informatics, Keio University, Japan) for kindly editing of the English manuscript of this webpage with helpful comments.</div>Noriko.hiroihttp://131.113.63.82/index.php?title=%E3%82%B3%E3%82%A2%E3%83%A1%E3%83%B3%E3%83%90%E3%83%BC%E4%B8%96%E8%A9%B1%E4%BA%BA%E4%B8%80%E8%A6%A7&diff=248232コアメンバー世話人一覧2023-01-10T06:15:20Z<p>Noriko.hiroi: </p>
<hr />
<div>==定量生物学の会 コアメンバー一覧 ==<br />
発生生物学・細胞生物学・分子生物学・生物物理学・1分子生物学・数理生物学・バイオインフォマティクス・バイオイメージング・生命工学などの、各分野を牽引してゆくポテンシャルと熱意を秘めていると思われる若手研究者が広く集まっています。<br />
<br />
*青木 一洋 (基礎生物学研究所)<br />
*伊藤 浩史 (九州大学芸術工学府デザイン人間科学コース)<br />
*内田 誠一 (九州大学大学院 システム情報科学研究院)<br />
*奥 寛雅 (群馬大学)<br />
*木村 暁 (国立遺伝学研究所)<br />
*国田 勝行 (藤田医科大学)<br />
*小林 徹也 (東京大学 生産技術研究所)<br />
*杉村 薫 (東京大学 理学系研究科)<br />
*鈴木 誉保 (東京大学 大学院新領域創成科学研究科)<br />
*鈴木 団 (大阪大学)<br />
*高木 拓明 (公立大学法人奈良県立医科大学 医学部)<br />
*塚田 祐基 (名古屋大学大学院 理学研究科)<br />
*寺前 順之介 (京都大学)<br />
*二階堂 愛 (独立行政法人理化学研究所 東京医科歯科大学)<br />
*野中 茂紀 (基礎生物学研究所)<br />
*日比野 佳代 (国立遺伝学研究所)<br />
*平島 剛志 (MBI)<br />
*広井 賀子 (神奈川工科大学創造工学部 & 慶應義塾大学医学部)<br />
*舟橋 啓 (慶應義塾大学 理工学部)<br />
*前多 裕介 (九州大学)<br />
*村田 隆 (神奈川工科大学応用バイオ科学科)<br />
<br /><br />
休部中:<br />
*荒田 幸信 (独立行政法人理化学研究所 基幹研究所)<br />
*石原 秀至 (東京大学大学院 総合文化研究科)<br />
*笠井 倫志 (京都大学 再生医科学研究所)<br />
*木下 和久 (独立行政法人理化学研究所 基幹研究所)<br />
*木村 啓志 (東海大学 機械工学科)<br />
*澤井 哲 (東京大学大学院 総合文化研究科)<br />
*筒井 秀和 (北陸先端大学)<br />
*原田 崇広<br />
*松林 完 (Bournemouth University)<br />
<br /><br />
<br />
==定量生物学の会 世話人一覧 ==<br />
*小林 徹也 (東京大学 生産技術研究所)<br />
*杉村 薫 (東京大学 理学系研究科)<br />
*高木 拓明 (公立大学法人奈良県立医科大学 医学部)<br />
*舟橋 啓 (慶應義塾大学 理工学部)</div>Noriko.hiroihttp://131.113.63.82/index.php?title=English&diff=129229English2022-09-13T06:06:43Z<p>Noriko.hiroi: /* Core members */</p>
<hr />
<div><span style="color: red">news!(19/10/2015)</span><br />
<br/><br />
We will hold<br/><br />
<span style="color: green">'''''NIG International Symposium 2016 + ROIS Event''''' <br><br />
and '''''Toyoda Physical & Chemical Research Institute Workshop''''' </span><br />
<br/>on Jan 8th ~ 13th, 2016.<br />
='''Japan q-bio week''' (Jan/8/2016~Jan/13/2016)=<br />
We have a series of international symposiums and workshops (Japan q-bio week) 8/Jan/2016 to 13/2016 instead of the annual meeting of the Japanese Society for Quantitative Biology. Most of them will be held as NIG International Symposium 2016. All these symposiums and workshops are organized by the core-members of Japanese Society for Quantitative Biology.<br />
<!-- This year's annual meeting of the Japanese Society for Quantitative Biology will be held as NIG International Symposium 2015, titled [[NIG_International_Symposium_2015_JapanQ-Bioweek|NIG INternational Symposium 2015: Japan Q-Bio week – force, information, and dynamics]] on Jan 7th to 11th, 2016 at Institute of Industrial Science, the University of Tokyo, and Jan 12th and 13th, 2016 at National Institute of Genetics. --><br />
<br />
*'''Tokyo Workshops'''<br />
** Date: Jan/8/2016<br />
** Site:Institute of Industrial Science, <span style="color: red"> Bld. S </span>, the Univ. Tokyo, Komaba<br />
***[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop (9:00 - 12:00)] '''Bridging Theory & Experiment'''<br />
***[http://symposium.crmind.net/EIC2015/Home.html Toyoda Physical & Chemical Research Institute Workshop (13:00 - 18:00)] '''Entropy, Information & Control'''<br><br />
<br />
*'''[[IIS_Sympo|NIG International Symposium - Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]]'''<br />
** Date:Jan/9/2016~Jan/11/2016<br />
** Site:Institute of Industrial Science, <span style="color: red">Bld. An</span>, the Univ Tokyo Komaba<br />
* '''[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html ROIS Event - Mishima Symposium:Quantitative Biology - force, information and dynamics]'''<br />
** Date:Jan/12/2016~Jan/13/2016<br />
** Site:National Institute of Genetics<br />
<br />
<br />
== What is the Japanese Society for Quantitative Biology <br>(Q-BioJP)? ==<br />
The '''Japanese Society for Quantitative Biology''' ('''Q-BioJP''') is a non-profit organization founded in 2008 that is dedicated to the advancement of the field of quantitative biology.<br><br />
The mission of the '''Q-BioJP''' is to<br />
* bring together the various fields of biological research that will benefit from quantitative analysis<br />
* provide an interdisciplinary forum for research, and to provide opportunities for collaboration in quantitative biology<br />
* promote the field of quantitative biology and to advance our understanding of biological systems.<br />
[[Main_Page|Japanese "Main Page"]]<br />
<br><br />
<br />
== Background of the foundation ==<br />
'''A PERIOD OF TRANSITION'''<br><br />
Biology is in a period of transition, from being a mostly descriptive and qualitative discipline towards being more analytical and quantitative. It is hoped that this change in emphasis will produce insights, and also new technologies. These approaches will be carried out by a new kind of biologist who can deal with the requirements of this new field.<br><br />
'''A FUTURE GOAL OF BIOLOGY'''<br><br />
While most of modern biology was focused on the properties of individual molecules, a future goal will be to understand their dynamics, and will require finding new ways of thinking and analysing these processes at a level beyond the individual components and their static properties. For solutions to these comprehensive questions, biology is now looking to other disciplines. Systems Biology has built strong links between Biology, Computer Sciences, and Mathematics to develop integrated approaches to deal with recent explosive increase in biological knowledge.<br><br />
'''HOW TO APPROACH THE PRINCIPLES'''<br><br />
Now to approach the principles that underlie their dynamical behaviors, the Physical and Chemical Sciences may provide a useful precedent. We also notice biological systems may have design principles that can be understood from an Engineering point of view.<br><br />
[[About_us|Japanese "About us"]]<br />
<br><br />
<br />
== The Aim of the Q-BioJP ==<br />
'''TO PROMOTE SPONTANEOUS ACTION'''<br><br />
Our purpose is to promote spontaneous action of each scientist for the development of quantitative biology.<br><br />
'''TO ESTABLISH AN INTERDISCIPLINARY ENVIRONMENT'''<br><br />
To achieve this objective we plan to establish an interdisciplinary research environment; such an environment will accelerate the natural convergence of different but related fields, and the expansion research into at the interface of different areas of research.<br><br />
The interactions fostered by us will transcend the boundaries between Biology and Physics, Chemistry, Engineering, Mathematics and Computational sciences.<br><br />
'''TO FORM A COMMUNITY FOR DEVELOPMENTS OF THE FIELD'''<br><br />
Above all, we aim to form a community that will be nourished by, and contribute to, the new developments which arise from the interdisciplinary research environment, and will provide the means for people with different approaches to related problems to come together and find novel and interesting solutions.<br><br />
[[About_us|Japanese "About us"]]<br />
<br><br />
<br />
== Targeting Subject ==<br />
We explore techniques and methods to quantify the physical properties that determine the dynamics of biological phenomena. Our main focus is on '''cellular-level biology''', but we are also concerned with the structure and organization of cells. The behavior of cells is influenced by events at '''a molecular level''' and upwards to '''the tissue and organism level'''. A new-generation model of Q-BioJP can take initiatives at '''medical sciences''' such as pharmacokinetics and cancer research. Q-BioJP will strive to understand the various levels of biological systems and the relationships that exist between them.<br><br />
[[About_us|Japanese "About us"]]<br />
<br><br />
<br />
== Agenda ==<br />
To these ends, we operate the following three strategies:<br />
====1. An annual meeting to - foster excellence in research and education -====<br />
We organize an annual scientific meeting which consists of technical tutorials and sessions focused on selected topics.<br><br />
* '''target audience''': Scientists that have already begun a research in the field of quantitative biology or have concrete plans to start.<br />
* '''objective''': The meeting provides a program for the interdisciplinary community of quantitative biologists to promote sharing of information to solve technical problems in their research, and to promote discussions of our future direction.<br />
<span style="color: green">The 5th Annual Meeting will be held on 23rd - 25th November 2012 at the Convention Hall in Institute of Industrial Science, the University of Tokyo. </span><br />
<br><br />
[[5th_Annual_Meeting|5th Annual Meeting]]<br><br />
[[Events|Japanese Events]]<br />
<br />
====2. Caravan - scholarly dissemination of research -====<br />
* '''target audience''': researchers who are interested in quantitative biology but require guidance in starting a research program in this area “quantitative biology”.<br />
* '''objective''': To showcase exciting examples of quantitative biology with an emphasis on the importance of the quantitative point of view in biology.<br />
<br />
====3. Mailing list====<br />
* '''objective''' : exchanging information on topics relating to quantitative biology.<br />
* '''members in the list''': '''There is no condition to participate our mailing list except your motivation'''. You can join anytime via a direct invitation by a core member. (<span style="color: green">This mailing list is basically managed in Japanese.</span>)<br />
<br><br />
<br />
===All are welcome who would strive together to ensure the future of this new basic scientific field!===<br />
<br><br />
<br><br />
==== Links in English on q-bio.jp ====<br />
*[http://www.iis.u-tokyo.ac.jp/What_e/What_e.html Institute of Industrial Science, the University of Tokyo][[Events|in "Events"]]<br />
*[http://www.med.osaka-u.ac.jp/index-e.html Graduate School of Medicine/Faculty of Medicine, Osaka University][[Events|in "Events"]]<br />
*[http://www.nig.ac.jp/index-e.html National Institute of Genetics][[Events|in "Events"]]<br />
*[http://www.jsbi.org/en Japanese Society for Bioinformatics][[Events|in "Events"]]<br />
*[http://www.springer.com/physics/book/978-3-540-40824-6 Synergetics by Hermann Haken][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.elsevierdirect.com/ISBN/9780123497031/Differential-Equations-Dynamical-Systems-and-an-Introduction-to-Chaos| Differential Equations Dynamical Systems and an Introduction to Chaos by Dr. Morris W. Hirsch, Dr. Stephen Smale and Dr. Robert Devaney][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.perseusbooks.com/perseus/book_detail.jsp?isbn=0738204536 Nonlinear Dynamics And Chaos With Applications To Physics, Biology, Chemistry, And Engineering by Steven H. Strogatz][[Documents|in "Documents", recommedned text books]]<br />
*[http://press.princeton.edu/titles/112.html Random Walks in Biology by Howard C. Berg][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.cambridge.org/us/catalogue/catalogue.asp?isbn=0521783372 Biological Physics of the Developing Embryo by Gabor Forgacs and Stuart A. Newman][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.springer.com/mathematics/mathematical+biology/book/978-0-387-75846-6 Mathematical Physiology by James Keener, James Sneyd][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.garlandscience.com/textbooks/0815341636.asp Physical Biology of the Cell by Rob Phillips, Jane Kondev, Julie Theriot][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.weizmann.ac.il/mcb/UriAlon/bookUri.html An Introduction to Systems Biology - Design Principles of Biological Circuits by Uri Alon][[Documents|in "Documents", recommedned text books]]<br />
*[http://www.micro-manager.org/| micromanager][[Documents|in "Documents", image processing tools]]<br />
*[http://www.mathworks.com/products/image/demos.html MathWorks Image Proecssing Toolbox][[Documents|in "Documents", image processing tools]]<br />
*[http://homepages.inf.ed.ac.uk/rbf/HIPR2 image processing learning resources][[Documents|in "Documents", image processing tools]]<br />
*[http://q-bio.jp/wiki/News#Biology.2FGenetics.2FEvolution_Postdoctoral_Fellow_Position.2C__Fred_Hutchinson_Cancer_Research_Center_.28091006.29_New.21.21 Biology/Genetics/Evolution Postdoctoral Fellow Position, Fred Hutchinson Cancer Research Center (091006)][[News|in "News", Job opportunity]]<br />
<br />
==Core members==<br />
*'''Kazuhiro Aoki''' (Kyoto University)<br />
*'''Yukinobu Arata''' (RIKEN, Advanced Science Institute)<br />
*'''Hiroshi Ito''' (Kyushu University)<br />
*'''Seiichi Uchida''' (Kyushu University)<br />
*'''Hiromasa Oku''' (Gunma University)<br />
*'''Akatsuki Kimura''' (Cell Architecture Laboratory, National Institute of Genetics)<br />
*'''Katsuyuki Kunida''' (NAIST)<br />
*'''Tetsuya J. Kobayashi''' (Institute of Industrial Science, the University of Tokyo)<br />
*'''Kaoru Sugimura''' (iCeMS, Kyoto University)<br />
*'''Takao K Suzuki''' (Graduate School of Science, the University of Tokyo)<br />
*'''Madoka Suzuki''' (Osaka University)<br />
*'''Hiroaki Takagi''' (Department of Physics, School of Medicine, Nara Medical University)<br />
*'''Jun-nosuke Teramae''' (Kyoto University)<br />
*'''Yuki Tsukada''' (Division of Biological Science, Graduate School of Science, Nagoya University)<br />
*'''Itoshi Nikaido''' (RIKEN)<br />
*'''Shigenori Nonaka''' (NIBB)<br />
*'''Kayo Hibino'''(National Institute of Genetics)<br />
*'''Tsuyoshi Hirashima''' (Kyoto University)<br />
*'''Noriko Hiroi''' (Kanagawa Institute of Technology & Keio University)<br />
*'''Akira Funahashi''' (Department of Biosciences and Informatics, Keio University)<br />
*'''Yusuke T. Maeda''' (Kyushu University)<br />
*'''Takashi Murata''' (NIBB)<br />
<br><br />
<br><br />
tentatively away:<br><br />
*'''Rinshi S. Kasai''' (Institute for Integrated Cell-Material Sciences,Kyoto University)<br />
*'''Shuji Ishihara''' (Meiji University)<br />
*'''Kazuhisa Kinoshita''' (RIKEN Advanced Science Institute)<br />
*'''Hiroshi Kimura''' (Department of Mechanical Engineering, Tokai University)<br />
*'''Satoshi Sawai''' (Graduate School of Arts and Sciences, University of Tokyo)<br />
*'''Hidekazu Tsutsui''' (JAIST)<br />
*'''Takahiro Harada'''<br />
*'''Yutaka Matsubayashi''' (King’s College London)<br />
<br />
== Acknowledgement ==<br />
We are grateful to Dr. Aitor Gonza ́ lez (Institute for Virus Research, Kyoto University, Japan) , Dr. Jonathan James Ward (Cellular architecture Group, Cell Biology and Biophysics Unit, EMBL-Heidelberg, Germany), Kris Popendorf (Bioinformatics Laboratory, Department of Bioscience and Informatics, Keio University, Japan) for kindly editing of the English manuscript of this webpage with helpful comments.</div>Noriko.hiroihttp://131.113.63.82/index.php?title=%E3%82%B3%E3%82%A2%E3%83%A1%E3%83%B3%E3%83%90%E3%83%BC%E4%B8%96%E8%A9%B1%E4%BA%BA%E4%B8%80%E8%A6%A7&diff=129226コアメンバー世話人一覧2022-09-13T06:05:52Z<p>Noriko.hiroi: /* 定量生物学の会 コアメンバー一覧 */</p>
<hr />
<div>==定量生物学の会 コアメンバー一覧 ==<br />
発生生物学・細胞生物学・分子生物学・生物物理学・1分子生物学・数理生物学・バイオインフォマティクス・バイオイメージング・生命工学などの、各分野を牽引してゆくポテンシャルと熱意を秘めていると思われる若手研究者が広く集まっています。<br />
<br />
*青木 一洋 (基礎生物学研究所)<br />
*荒田 幸信 (独立行政法人理化学研究所 基幹研究所)<br />
*伊藤 浩史 (九州大学芸術工学府デザイン人間科学コース)<br />
*内田 誠一 (九州大学大学院 システム情報科学研究院)<br />
*奥 寛雅 (群馬大学)<br />
*木村 暁 (国立遺伝学研究所)<br />
*国田 勝行 (奈良先端科学技術大学院大学)<br />
*小林 徹也 (東京大学 生産技術研究所)<br />
*杉村 薫 (東京大学 理学系研究科)<br />
*鈴木 誉保 (東京大学 大学院新領域創成科学研究科)<br />
*鈴木 団 (大阪大学)<br />
*高木 拓明 (公立大学法人奈良県立医科大学 医学部)<br />
*塚田 祐基 (名古屋大学大学院 理学研究科)<br />
*寺前 順之介 (京都大学)<br />
*二階堂 愛 (独立行政法人理化学研究所)<br />
*野中 茂紀 (基礎生物学研究所)<br />
*日比野 佳代 (国立遺伝学研究所)<br />
*平島 剛志 (京都大学)<br />
*広井 賀子 (神奈川工科大学創造工学部 & 慶應義塾大学医学部)<br />
*舟橋 啓 (慶應義塾大学 理工学部)<br />
*前多 裕介 (九州大学)<br />
*村田 隆 (基礎生物学研究所)<br />
<br /><br />
休部中:<br />
*石原 秀至 (東京大学大学院 総合文化研究科)<br />
*笠井 倫志 (京都大学 再生医科学研究所)<br />
*木下 和久 (独立行政法人理化学研究所 基幹研究所)<br />
*木村 啓志 (東海大学 機械工学科)<br />
*澤井 哲 (東京大学大学院 総合文化研究科)<br />
*筒井 秀和 (北陸先端大学)<br />
*原田 崇広<br />
*松林 完 (King’s College London)<br />
<br /><br />
<br />
==定量生物学の会 世話人一覧 ==<br />
*小林 徹也 (東京大学 生産技術研究所)<br />
*杉村 薫 (東京大学 理学系研究科)<br />
*高木 拓明 (公立大学法人奈良県立医科大学 医学部)<br />
*舟橋 啓 (慶應義塾大学 理工学部)</div>Noriko.hiroihttp://131.113.63.82/index.php?title=About_us&diff=129225About us2022-09-13T06:04:54Z<p>Noriko.hiroi: </p>
<hr />
<div>== 定量生物学の会の概要 ==<br />
[[English| go to English page]] <br />
=== 背景 ===<br />
現在、生命科学の多数の領域において、定量的なアプローチを導入した研究が分子生物学を補完する1つの方向性として浮上しつつあり、すでに萌芽的な研究例が報告されています。<br />
<br />
「定量生物学の会」はこのような背景のもと、各領域において自ら手を動かして定量的な生命科学を模索している若手研究者により2回の準備会を経て立ち上げられた研究グループです。<br />
<br />
[https://q-bio.jp/index.php?title=English#Background_of_the_foundation Background of the foundation(English)]<br />
<br />
=== 会の目的 ===<br />
本研究会は定量的な生命科学の方向性・問題点などを具体的に議論し、領域横断的な研究体制や連携関係をトップダウン的にではなく、最前線の研究を担う若手研究者(学生、PD、若手PI)によってボトムアップ的に模索することを目的としています。<br />
<br />
[https://q-bio.jp/index.php?title=English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 会の活動 ===<br />
メーリングリストによる情報交換(参加はコアメンバーによる紹介制)と、以下に述べます2つの目的の異なる研究会の開催を行っています。<br />
<br />
1つ目は「'''年会'''」と呼ばれる会です。定量的な生命科学研究に携わる・もしくは携わりたいと考えている研究者どうしが集まって相互に情報を発信することで、技術的な問題の解決方法や今後の研究の方向性などを模索することを目指します。<br />
<br />
2つ目は「'''キャラバン'''」と呼ばれる会です。(主に)定量生物学に携わっていないが興味を抱いている研究者に向けて、定量的な生命科学研究の重要性や成果を発信する会です。2009年3月に初回のキャラバンを「遺伝研」で開催しました。今後も、様々な研究機関で開催したいと考えています。<br />
<br />
[https://q-bio.jp/index.php?title=English#Agenda Agenda (English)]<br />
<br />
=== コアメンバー・世話人===<br />
*[[コアメンバー世話人一覧|コアメンバー・世話人の一覧]]<br />
*[https://q-bio.jp/index.php?title=English#Core_members Core members]<br />
<br />
=== 研究会のウェブサイト ===<br />
URL: http://q-bio.jp/<br />
<br><br />
URL (English page): https://q-bio.jp/index.php?title=English<br />
<br />
=== 研究会の問い合わせ先 ===<br />
連絡先:q.biology at gmail.com<br />
(迷惑メール対策のため@をatと表示しています。at を @ に置換してください)<br />
<br />
== 我々が考える定量生物学 2008 ==<br />
定量的なデータ解析は生命科学の様々な分野において行われており、すべてを本研究会で網羅することは現実的でないと考えています。そこで、あくまで本研究会が対象に設定している定量生物学であることを明示するために、「我々が考える定量生物学」というタイトルにしました。また、「我々が考える定量生物学」も未成熟であり、今後色々な人と議論を交わす過程で変わっていくと思います。変わっていく過程、外部からの意見を取り入れる姿勢を示すという意味で、各年度ごとに定義を更新していくのもおもしろいかと考えました。そのため2008という日付を入れてあります。<br />
<br />
=== なぜ定量生物学が再び注目されてきているのか?===<br />
定量的な生命科学が注目されてきている背景として、イメージングなどの光学技術、MEMSなどの工学技術の発展に伴い、より解像度の高い時空間情報を得られるようになったことが挙げられます。また、実験・解析技術の異分野間交流が進み、それにともなって優れた定量解析から生命システムの原理に迫る研究が分野を超えて認識されるようになってきたことも背景の一つに挙げられます。<br />
<br />
例えば主に分子生物学的手法を用いてきた細胞生物学や発生生物学では、バイオイメージングなどの発展によりこれまで見過ごされてきた、あるいは解析できなかった分子レベル、細胞レベルの現象を詳細に可視化できるようになりました。それにともない、現象を定量的に解析すること、そしてそのための数理、実験手法の必要性が認識されるようになってきました。このような流れは、定量的な解析が分子生物学成立直後までは活発に行われていたことを考えると、ルネッサンス的な意味を持っていると考えられます。<br />
<br />
一方で生物物理学においては、バイオイメージングなどを駆使した定量的な解析は継続的に行われてきましたが、逆にスクリーニングなどの分子生物学的な研究はあまり集中的に行われてきませんでした。しかし最近、生物物理学の方法論と分子生物学の方法論の双方を使いこなす若手研究者が現れ、融合的な研究の機運が高まってきています。また、これまでタンパク質構造などの分子レベルの現象と比較して比重が低かった細胞レベルの現象や個体発生に挑む研究者も増加傾向にあり、細胞や組織のスケールにおける定量的な研究が顕在化してきているという背景もあります。<br />
<br />
さらに、理論系研究においては、利用可能な定量的な実験データが限られていた時代の理論生物学のスタイルから脱却した、定量的な実験データの存在を前提とする現代的な理論生物学が求められています。またインフォマティクスでは、分子生物学の発展に立脚したオミクス情報を対象とした研究だけでなく、オミクス情報ほど網羅的ではないがより定量性の高いデータという新しい種類の情報を対象としたインフォマティクスの可能性を探る試みがなされてきています。<br />
<br />
このように定量生物学は、生命科学の様々な分野における新しい流れが結びついた異分野融合の交差点に位置していると考えられます。そして「定量生物学の会」は、定量的な生命科学に挑戦する様々な分野の若手研究者が、その技術や知見を交換をする場としての役割を担っていきたいと考えています。しかし研究会としては、'''定量的な研究はあくまで手段であって、我々の最終的な目的はこれまで明らかにされていない生命現象の謎を解くことにある'''と考えています。<br />
<br />
[https://q-bio.jp/index.php?title=English#Background_of_the_foundation Background of the foundation (English)]<br />
<br><br />
[https://q-bio.jp/index.php?title=English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 我々が現在想定している定量生物学の研究対象 ===<br />
定量的なデータ解析は生命科学の様々な分野において行われており、そのすべてを本研究会で網羅することは現実的でないと考えています。本研究会が現時点でターゲットとしている研究は、まず過去に定量的な方法論を使っていたにもかかわらず、分子生物学による定性分析の台頭によって、定量的な思考や方法論が衰退してしまった分野です。例えば発生学はこのような分野の1例であると考えられます。このような分野では定量的な思考や手法が遅れている分、それらを導入することにより生命現象の理解が格段に進む可能性があります。<br />
<br />
他方で、生物物理学における細胞ダイナミクスの解析など、定量的な解析手法の適用範囲を多階層のスケールを横断する形で拡張する境界領域分野も主要な対象とします。解析対象は分子から個体までを含みますが、特に細胞・組織の階層を含む研究を中心に据えます。分子、個体においては、それぞれ、より高次・低次の現象との関係を意識したものに積極的に取り組み、分子と分子内部分構造などは重点的には扱いません。<br />
<br />
さらに、理論系研究においてはアイディア・モデルのみに動機づけられた研究よりも、定量的なデータや知見を積極的に取り入れた理論を模索する研究を現時点では想定しています。また、画像データから定量性の高い時空間情報を抽出することが現在の定量生物学におけるデータ生産のボトルネックになっていることから、画像解析を中心としたインフォマティクスの研究も歓迎します。<br />
<br />
神経科学は伝統的に定量性を意識した研究がなされてきた分野でありますが、すでに電気生理データなどの定量的な解析手法が比較的成熟しているため、現時点では対象に含めていません。ただし、神経科学と他分野を定量的な解析手法でつなぐ横断的研究(成長円錐の走性・神経細胞内の1分子計測・神経発生)などは対象に含めます。<br />
<br />
また、マイクロアレイなどの網羅的な解析を中心とした研究も現時点では対象に含めていません。ただし、網羅的な解析を発展させ、高い定量性持たせることを追求するような研究については対象に含めます。<br />
<br />
[https://q-bio.jp/index.php?title=English#Targeting_Subject Trageting Subgect (English)]</div>Noriko.hiroihttp://131.113.63.82/index.php?title=About_us&diff=129222About us2022-09-13T06:02:42Z<p>Noriko.hiroi: /* なぜ定量生物学が再び注目されてきているのか? */</p>
<hr />
<div>== 定量生物学の会の概要 ==<br />
[[English| go to English page]] <br />
=== 背景 ===<br />
現在、生命科学の多数の領域において、定量的なアプローチを導入した研究が分子生物学を補完する1つの方向性として浮上しつつあり、すでに萌芽的な研究例が報告されています。<br />
<br />
「定量生物学の会」はこのような背景のもと、各領域において自ら手を動かして定量的な生命科学を模索している若手研究者により2回の準備会を経て立ち上げられた研究グループです。<br />
<br />
[https://q-bio.jp/index.php?title=English#Background_of_the_foundation Background of the foundation(English)]<br />
<br />
=== 会の目的 ===<br />
本研究会は定量的な生命科学の方向性・問題点などを具体的に議論し、領域横断的な研究体制や連携関係をトップダウン的にではなく、最前線の研究を担う若手研究者(学生、PD、若手PI)によってボトムアップ的に模索することを目的としています。<br />
<br />
[https://q-bio.jp/index.php?title=English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 会の活動 ===<br />
メーリングリストによる情報交換(参加はコアメンバーによる紹介制)と、以下に述べます2つの目的の異なる研究会の開催を行っています。<br />
<br />
1つ目は「'''年会'''」と呼ばれる会です。定量的な生命科学研究に携わる・もしくは携わりたいと考えている研究者どうしが集まって相互に情報を発信することで、技術的な問題の解決方法や今後の研究の方向性などを模索することを目指します。<br />
<br />
2つ目は「'''キャラバン'''」と呼ばれる会です。(主に)定量生物学に携わっていないが興味を抱いている研究者に向けて、定量的な生命科学研究の重要性や成果を発信する会です。2009年3月に初回のキャラバンを「遺伝研」で開催しました。今後も、様々な研究機関で開催したいと考えています。<br />
<br />
[https://q-bio.jp/index.php?title=English#Agenda Agenda (English)]<br />
<br />
=== コアメンバー・世話人===<br />
*[[コアメンバー世話人一覧|コアメンバー・世話人の一覧]]<br />
*[https://q-bio.jp/index.php?title=English#Core_members Core members]<br />
<br />
=== 研究会のウェブサイト ===<br />
URL: http://q-bio.jp/<br />
<br><br />
URL (English page): https://q-bio.jp/index.php?title=English<br />
<br />
=== 研究会の問い合わせ先 ===<br />
連絡先:q.biology at gmail.com<br />
(迷惑メール対策のため@をatと表示しています。at を @ に置換してください)<br />
<br />
== 我々が考える定量生物学 2008 ==<br />
定量的なデータ解析は生命科学の様々な分野において行われており、すべてを本研究会で網羅することは現実的でないと考えています。そこで、あくまで本研究会が対象に設定している定量生物学であることを明示するために、「我々が考える定量生物学」というタイトルにしました。また、「我々が考える定量生物学」も未成熟であり、今後色々な人と議論を交わす過程で変わっていくと思います。変わっていく過程、外部からの意見を取り入れる姿勢を示すという意味で、各年度ごとに定義を更新していくのもおもしろいかと考えました。そのため2008という日付を入れてあります。<br />
<br />
=== なぜ定量生物学が再び注目されてきているのか?===<br />
定量的な生命科学が注目されてきている背景として、イメージングなどの光学技術、MEMSなどの工学技術の発展に伴い、より解像度の高い時空間情報を得られるようになったことが挙げられます。また、実験・解析技術の異分野間交流が進み、それにともなって優れた定量解析から生命システムの原理に迫る研究が分野を超えて認識されるようになってきたことも背景の一つに挙げられます。<br />
<br />
例えば主に分子生物学的手法を用いてきた細胞生物学や発生生物学では、バイオイメージングなどの発展によりこれまで見過ごされてきた、あるいは解析できなかった分子レベル、細胞レベルの現象を詳細に可視化できるようになりました。それにともない、現象を定量的に解析すること、そしてそのための数理、実験手法の必要性が認識されるようになってきました。このような流れは、定量的な解析が分子生物学成立直後までは活発に行われていたことを考えると、ルネッサンス的な意味を持っていると考えられます。<br />
<br />
一方で生物物理学においては、バイオイメージングなどを駆使した定量的な解析は継続的に行われてきましたが、逆にスクリーニングなどの分子生物学的な研究はあまり集中的に行われてきませんでした。しかし最近、生物物理学の方法論と分子生物学の方法論の双方を使いこなす若手研究者が現れ、融合的な研究の機運が高まってきています。また、これまでタンパク質構造などの分子レベルの現象と比較して比重が低かった細胞レベルの現象や個体発生に挑む研究者も増加傾向にあり、細胞や組織のスケールにおける定量的な研究が顕在化してきているという背景もあります。<br />
<br />
さらに、理論系研究においては、利用可能な定量的な実験データが限られていた時代の理論生物学のスタイルから脱却した、定量的な実験データの存在を前提とする現代的な理論生物学が求められています。またインフォマティクスでは、分子生物学の発展に立脚したオミクス情報を対象とした研究だけでなく、オミクス情報ほど網羅的ではないがより定量性の高いデータという新しい種類の情報を対象としたインフォマティクスの可能性を探る試みがなされてきています。<br />
<br />
このように定量生物学は、生命科学の様々な分野における新しい流れが結びついた異分野融合の交差点に位置していると考えられます。そして「定量生物学の会」は、定量的な生命科学に挑戦する様々な分野の若手研究者が、その技術や知見を交換をする場としての役割を担っていきたいと考えています。しかし研究会としては、'''定量的な研究はあくまで手段であって、我々の最終的な目的はこれまで明らかにされていない生命現象の謎を解くことにある'''と考えています。<br />
<br />
[https://q-bio.jp/index.php?title=English#Background_of_the_foundation Background of the foundation (English)]<br />
<br><br />
[https://q-bio.jp/index.php?title=English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 我々が現在想定している定量生物学の研究対象 ===<br />
定量的なデータ解析は生命科学の様々な分野において行われており、そのすべてを本研究会で網羅することは現実的でないと考えています。本研究会が現時点でターゲットとしている研究は、まず過去に定量的な方法論を使っていたにもかかわらず、分子生物学による定性分析の台頭によって、定量的な思考や方法論が衰退してしまった分野です。例えば発生学はこのような分野の1例であると考えられます。このような分野では定量的な思考や手法が遅れている分、それらを導入することにより生命現象の理解が格段に進む可能性があります。<br />
<br />
他方で、生物物理学における細胞ダイナミクスの解析など、定量的な解析手法の適用範囲を多階層のスケールを横断する形で拡張する境界領域分野も主要な対象とします。解析対象は分子から個体までを含みますが、特に細胞・組織の階層を含む研究を中心に据えます。分子、個体においては、それぞれ、より高次・低次の現象との関係を意識したものに積極的に取り組み、分子と分子内部分構造などは重点的には扱いません。<br />
<br />
さらに、理論系研究においてはアイディア・モデルのみに動機づけられた研究よりも、定量的なデータや知見を積極的に取り入れた理論を模索する研究を現時点では想定しています。また、画像データから定量性の高い時空間情報を抽出することが現在の定量生物学におけるデータ生産のボトルネックになっていることから、画像解析を中心としたインフォマティクスの研究も歓迎します。<br />
<br />
神経科学は伝統的に定量性を意識した研究がなされてきた分野でありますが、すでに電気生理データなどの定量的な解析手法が比較的成熟しているため、現時点では対象に含めていません。ただし、神経科学と他分野を定量的な解析手法でつなぐ横断的研究(成長円錐の走性・神経細胞内の1分子計測・神経発生)などは対象に含めます。<br />
<br />
また、マイクロアレイなどの網羅的な解析を中心とした研究も現時点では対象に含めていません。ただし、網羅的な解析を発展させ、高い定量性持たせることを追求するような研究については対象に含めます。<br />
<br />
[http://www.q-bio.jp/wiki/English#Targeting_Subject Trageting Subgect (English)]</div>Noriko.hiroihttp://131.113.63.82/index.php?title=About_us&diff=129218About us2022-09-13T06:01:48Z<p>Noriko.hiroi: /* 研究会のウェブサイト */</p>
<hr />
<div>== 定量生物学の会の概要 ==<br />
[[English| go to English page]] <br />
=== 背景 ===<br />
現在、生命科学の多数の領域において、定量的なアプローチを導入した研究が分子生物学を補完する1つの方向性として浮上しつつあり、すでに萌芽的な研究例が報告されています。<br />
<br />
「定量生物学の会」はこのような背景のもと、各領域において自ら手を動かして定量的な生命科学を模索している若手研究者により2回の準備会を経て立ち上げられた研究グループです。<br />
<br />
[https://q-bio.jp/index.php?title=English#Background_of_the_foundation Background of the foundation(English)]<br />
<br />
=== 会の目的 ===<br />
本研究会は定量的な生命科学の方向性・問題点などを具体的に議論し、領域横断的な研究体制や連携関係をトップダウン的にではなく、最前線の研究を担う若手研究者(学生、PD、若手PI)によってボトムアップ的に模索することを目的としています。<br />
<br />
[https://q-bio.jp/index.php?title=English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 会の活動 ===<br />
メーリングリストによる情報交換(参加はコアメンバーによる紹介制)と、以下に述べます2つの目的の異なる研究会の開催を行っています。<br />
<br />
1つ目は「'''年会'''」と呼ばれる会です。定量的な生命科学研究に携わる・もしくは携わりたいと考えている研究者どうしが集まって相互に情報を発信することで、技術的な問題の解決方法や今後の研究の方向性などを模索することを目指します。<br />
<br />
2つ目は「'''キャラバン'''」と呼ばれる会です。(主に)定量生物学に携わっていないが興味を抱いている研究者に向けて、定量的な生命科学研究の重要性や成果を発信する会です。2009年3月に初回のキャラバンを「遺伝研」で開催しました。今後も、様々な研究機関で開催したいと考えています。<br />
<br />
[https://q-bio.jp/index.php?title=English#Agenda Agenda (English)]<br />
<br />
=== コアメンバー・世話人===<br />
*[[コアメンバー世話人一覧|コアメンバー・世話人の一覧]]<br />
*[https://q-bio.jp/index.php?title=English#Core_members Core members]<br />
<br />
=== 研究会のウェブサイト ===<br />
URL: http://q-bio.jp/<br />
<br><br />
URL (English page): https://q-bio.jp/index.php?title=English<br />
<br />
=== 研究会の問い合わせ先 ===<br />
連絡先:q.biology at gmail.com<br />
(迷惑メール対策のため@をatと表示しています。at を @ に置換してください)<br />
<br />
== 我々が考える定量生物学 2008 ==<br />
定量的なデータ解析は生命科学の様々な分野において行われており、すべてを本研究会で網羅することは現実的でないと考えています。そこで、あくまで本研究会が対象に設定している定量生物学であることを明示するために、「我々が考える定量生物学」というタイトルにしました。また、「我々が考える定量生物学」も未成熟であり、今後色々な人と議論を交わす過程で変わっていくと思います。変わっていく過程、外部からの意見を取り入れる姿勢を示すという意味で、各年度ごとに定義を更新していくのもおもしろいかと考えました。そのため2008という日付を入れてあります。<br />
<br />
=== なぜ定量生物学が再び注目されてきているのか?===<br />
定量的な生命科学が注目されてきている背景として、イメージングなどの光学技術、MEMSなどの工学技術の発展に伴い、より解像度の高い時空間情報を得られるようになったことが挙げられます。また、実験・解析技術の異分野間交流が進み、それにともなって優れた定量解析から生命システムの原理に迫る研究が分野を超えて認識されるようになってきたことも背景の一つに挙げられます。<br />
<br />
例えば主に分子生物学的手法を用いてきた細胞生物学や発生生物学では、バイオイメージングなどの発展によりこれまで見過ごされてきた、あるいは解析できなかった分子レベル、細胞レベルの現象を詳細に可視化できるようになりました。それにともない、現象を定量的に解析すること、そしてそのための数理、実験手法の必要性が認識されるようになってきました。このような流れは、定量的な解析が分子生物学成立直後までは活発に行われていたことを考えると、ルネッサンス的な意味を持っていると考えられます。<br />
<br />
一方で生物物理学においては、バイオイメージングなどを駆使した定量的な解析は継続的に行われてきましたが、逆にスクリーニングなどの分子生物学的な研究はあまり集中的に行われてきませんでした。しかし最近、生物物理学の方法論と分子生物学の方法論の双方を使いこなす若手研究者が現れ、融合的な研究の機運が高まってきています。また、これまでタンパク質構造などの分子レベルの現象と比較して比重が低かった細胞レベルの現象や個体発生に挑む研究者も増加傾向にあり、細胞や組織のスケールにおける定量的な研究が顕在化してきているという背景もあります。<br />
<br />
さらに、理論系研究においては、利用可能な定量的な実験データが限られていた時代の理論生物学のスタイルから脱却した、定量的な実験データの存在を前提とする現代的な理論生物学が求められています。またインフォマティクスでは、分子生物学の発展に立脚したオミクス情報を対象とした研究だけでなく、オミクス情報ほど網羅的ではないがより定量性の高いデータという新しい種類の情報を対象としたインフォマティクスの可能性を探る試みがなされてきています。<br />
<br />
このように定量生物学は、生命科学の様々な分野における新しい流れが結びついた異分野融合の交差点に位置していると考えられます。そして「定量生物学の会」は、定量的な生命科学に挑戦する様々な分野の若手研究者が、その技術や知見を交換をする場としての役割を担っていきたいと考えています。しかし研究会としては、'''定量的な研究はあくまで手段であって、我々の最終的な目的はこれまで明らかにされていない生命現象の謎を解くことにある'''と考えています。<br />
<br />
[http://www.q-bio.jp/wiki/English#Background_of_the_foundation Background of the foundation (English)]<br />
<br><br />
[http://www.q-bio.jp/wiki/English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 我々が現在想定している定量生物学の研究対象 ===<br />
定量的なデータ解析は生命科学の様々な分野において行われており、そのすべてを本研究会で網羅することは現実的でないと考えています。本研究会が現時点でターゲットとしている研究は、まず過去に定量的な方法論を使っていたにもかかわらず、分子生物学による定性分析の台頭によって、定量的な思考や方法論が衰退してしまった分野です。例えば発生学はこのような分野の1例であると考えられます。このような分野では定量的な思考や手法が遅れている分、それらを導入することにより生命現象の理解が格段に進む可能性があります。<br />
<br />
他方で、生物物理学における細胞ダイナミクスの解析など、定量的な解析手法の適用範囲を多階層のスケールを横断する形で拡張する境界領域分野も主要な対象とします。解析対象は分子から個体までを含みますが、特に細胞・組織の階層を含む研究を中心に据えます。分子、個体においては、それぞれ、より高次・低次の現象との関係を意識したものに積極的に取り組み、分子と分子内部分構造などは重点的には扱いません。<br />
<br />
さらに、理論系研究においてはアイディア・モデルのみに動機づけられた研究よりも、定量的なデータや知見を積極的に取り入れた理論を模索する研究を現時点では想定しています。また、画像データから定量性の高い時空間情報を抽出することが現在の定量生物学におけるデータ生産のボトルネックになっていることから、画像解析を中心としたインフォマティクスの研究も歓迎します。<br />
<br />
神経科学は伝統的に定量性を意識した研究がなされてきた分野でありますが、すでに電気生理データなどの定量的な解析手法が比較的成熟しているため、現時点では対象に含めていません。ただし、神経科学と他分野を定量的な解析手法でつなぐ横断的研究(成長円錐の走性・神経細胞内の1分子計測・神経発生)などは対象に含めます。<br />
<br />
また、マイクロアレイなどの網羅的な解析を中心とした研究も現時点では対象に含めていません。ただし、網羅的な解析を発展させ、高い定量性持たせることを追求するような研究については対象に含めます。<br />
<br />
[http://www.q-bio.jp/wiki/English#Targeting_Subject Trageting Subgect (English)]</div>Noriko.hiroihttp://131.113.63.82/index.php?title=About_us&diff=129217About us2022-09-13T06:01:13Z<p>Noriko.hiroi: /* コアメンバー・世話人 */</p>
<hr />
<div>== 定量生物学の会の概要 ==<br />
[[English| go to English page]] <br />
=== 背景 ===<br />
現在、生命科学の多数の領域において、定量的なアプローチを導入した研究が分子生物学を補完する1つの方向性として浮上しつつあり、すでに萌芽的な研究例が報告されています。<br />
<br />
「定量生物学の会」はこのような背景のもと、各領域において自ら手を動かして定量的な生命科学を模索している若手研究者により2回の準備会を経て立ち上げられた研究グループです。<br />
<br />
[https://q-bio.jp/index.php?title=English#Background_of_the_foundation Background of the foundation(English)]<br />
<br />
=== 会の目的 ===<br />
本研究会は定量的な生命科学の方向性・問題点などを具体的に議論し、領域横断的な研究体制や連携関係をトップダウン的にではなく、最前線の研究を担う若手研究者(学生、PD、若手PI)によってボトムアップ的に模索することを目的としています。<br />
<br />
[https://q-bio.jp/index.php?title=English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 会の活動 ===<br />
メーリングリストによる情報交換(参加はコアメンバーによる紹介制)と、以下に述べます2つの目的の異なる研究会の開催を行っています。<br />
<br />
1つ目は「'''年会'''」と呼ばれる会です。定量的な生命科学研究に携わる・もしくは携わりたいと考えている研究者どうしが集まって相互に情報を発信することで、技術的な問題の解決方法や今後の研究の方向性などを模索することを目指します。<br />
<br />
2つ目は「'''キャラバン'''」と呼ばれる会です。(主に)定量生物学に携わっていないが興味を抱いている研究者に向けて、定量的な生命科学研究の重要性や成果を発信する会です。2009年3月に初回のキャラバンを「遺伝研」で開催しました。今後も、様々な研究機関で開催したいと考えています。<br />
<br />
[https://q-bio.jp/index.php?title=English#Agenda Agenda (English)]<br />
<br />
=== コアメンバー・世話人===<br />
*[[コアメンバー世話人一覧|コアメンバー・世話人の一覧]]<br />
*[https://q-bio.jp/index.php?title=English#Core_members Core members]<br />
<br />
=== 研究会のウェブサイト ===<br />
URL: http://q-bio.jp/<br />
<br><br />
URL (English page): http://q-bio.jp/wiki/English<br />
<br />
=== 研究会の問い合わせ先 ===<br />
連絡先:q.biology at gmail.com<br />
(迷惑メール対策のため@をatと表示しています。at を @ に置換してください)<br />
<br />
== 我々が考える定量生物学 2008 ==<br />
定量的なデータ解析は生命科学の様々な分野において行われており、すべてを本研究会で網羅することは現実的でないと考えています。そこで、あくまで本研究会が対象に設定している定量生物学であることを明示するために、「我々が考える定量生物学」というタイトルにしました。また、「我々が考える定量生物学」も未成熟であり、今後色々な人と議論を交わす過程で変わっていくと思います。変わっていく過程、外部からの意見を取り入れる姿勢を示すという意味で、各年度ごとに定義を更新していくのもおもしろいかと考えました。そのため2008という日付を入れてあります。<br />
<br />
=== なぜ定量生物学が再び注目されてきているのか?===<br />
定量的な生命科学が注目されてきている背景として、イメージングなどの光学技術、MEMSなどの工学技術の発展に伴い、より解像度の高い時空間情報を得られるようになったことが挙げられます。また、実験・解析技術の異分野間交流が進み、それにともなって優れた定量解析から生命システムの原理に迫る研究が分野を超えて認識されるようになってきたことも背景の一つに挙げられます。<br />
<br />
例えば主に分子生物学的手法を用いてきた細胞生物学や発生生物学では、バイオイメージングなどの発展によりこれまで見過ごされてきた、あるいは解析できなかった分子レベル、細胞レベルの現象を詳細に可視化できるようになりました。それにともない、現象を定量的に解析すること、そしてそのための数理、実験手法の必要性が認識されるようになってきました。このような流れは、定量的な解析が分子生物学成立直後までは活発に行われていたことを考えると、ルネッサンス的な意味を持っていると考えられます。<br />
<br />
一方で生物物理学においては、バイオイメージングなどを駆使した定量的な解析は継続的に行われてきましたが、逆にスクリーニングなどの分子生物学的な研究はあまり集中的に行われてきませんでした。しかし最近、生物物理学の方法論と分子生物学の方法論の双方を使いこなす若手研究者が現れ、融合的な研究の機運が高まってきています。また、これまでタンパク質構造などの分子レベルの現象と比較して比重が低かった細胞レベルの現象や個体発生に挑む研究者も増加傾向にあり、細胞や組織のスケールにおける定量的な研究が顕在化してきているという背景もあります。<br />
<br />
さらに、理論系研究においては、利用可能な定量的な実験データが限られていた時代の理論生物学のスタイルから脱却した、定量的な実験データの存在を前提とする現代的な理論生物学が求められています。またインフォマティクスでは、分子生物学の発展に立脚したオミクス情報を対象とした研究だけでなく、オミクス情報ほど網羅的ではないがより定量性の高いデータという新しい種類の情報を対象としたインフォマティクスの可能性を探る試みがなされてきています。<br />
<br />
このように定量生物学は、生命科学の様々な分野における新しい流れが結びついた異分野融合の交差点に位置していると考えられます。そして「定量生物学の会」は、定量的な生命科学に挑戦する様々な分野の若手研究者が、その技術や知見を交換をする場としての役割を担っていきたいと考えています。しかし研究会としては、'''定量的な研究はあくまで手段であって、我々の最終的な目的はこれまで明らかにされていない生命現象の謎を解くことにある'''と考えています。<br />
<br />
[http://www.q-bio.jp/wiki/English#Background_of_the_foundation Background of the foundation (English)]<br />
<br><br />
[http://www.q-bio.jp/wiki/English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 我々が現在想定している定量生物学の研究対象 ===<br />
定量的なデータ解析は生命科学の様々な分野において行われており、そのすべてを本研究会で網羅することは現実的でないと考えています。本研究会が現時点でターゲットとしている研究は、まず過去に定量的な方法論を使っていたにもかかわらず、分子生物学による定性分析の台頭によって、定量的な思考や方法論が衰退してしまった分野です。例えば発生学はこのような分野の1例であると考えられます。このような分野では定量的な思考や手法が遅れている分、それらを導入することにより生命現象の理解が格段に進む可能性があります。<br />
<br />
他方で、生物物理学における細胞ダイナミクスの解析など、定量的な解析手法の適用範囲を多階層のスケールを横断する形で拡張する境界領域分野も主要な対象とします。解析対象は分子から個体までを含みますが、特に細胞・組織の階層を含む研究を中心に据えます。分子、個体においては、それぞれ、より高次・低次の現象との関係を意識したものに積極的に取り組み、分子と分子内部分構造などは重点的には扱いません。<br />
<br />
さらに、理論系研究においてはアイディア・モデルのみに動機づけられた研究よりも、定量的なデータや知見を積極的に取り入れた理論を模索する研究を現時点では想定しています。また、画像データから定量性の高い時空間情報を抽出することが現在の定量生物学におけるデータ生産のボトルネックになっていることから、画像解析を中心としたインフォマティクスの研究も歓迎します。<br />
<br />
神経科学は伝統的に定量性を意識した研究がなされてきた分野でありますが、すでに電気生理データなどの定量的な解析手法が比較的成熟しているため、現時点では対象に含めていません。ただし、神経科学と他分野を定量的な解析手法でつなぐ横断的研究(成長円錐の走性・神経細胞内の1分子計測・神経発生)などは対象に含めます。<br />
<br />
また、マイクロアレイなどの網羅的な解析を中心とした研究も現時点では対象に含めていません。ただし、網羅的な解析を発展させ、高い定量性持たせることを追求するような研究については対象に含めます。<br />
<br />
[http://www.q-bio.jp/wiki/English#Targeting_Subject Trageting Subgect (English)]</div>Noriko.hiroihttp://131.113.63.82/index.php?title=About_us&diff=129209About us2022-09-13T06:00:15Z<p>Noriko.hiroi: /* 会の活動 */</p>
<hr />
<div>== 定量生物学の会の概要 ==<br />
[[English| go to English page]] <br />
=== 背景 ===<br />
現在、生命科学の多数の領域において、定量的なアプローチを導入した研究が分子生物学を補完する1つの方向性として浮上しつつあり、すでに萌芽的な研究例が報告されています。<br />
<br />
「定量生物学の会」はこのような背景のもと、各領域において自ら手を動かして定量的な生命科学を模索している若手研究者により2回の準備会を経て立ち上げられた研究グループです。<br />
<br />
[https://q-bio.jp/index.php?title=English#Background_of_the_foundation Background of the foundation(English)]<br />
<br />
=== 会の目的 ===<br />
本研究会は定量的な生命科学の方向性・問題点などを具体的に議論し、領域横断的な研究体制や連携関係をトップダウン的にではなく、最前線の研究を担う若手研究者(学生、PD、若手PI)によってボトムアップ的に模索することを目的としています。<br />
<br />
[https://q-bio.jp/index.php?title=English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 会の活動 ===<br />
メーリングリストによる情報交換(参加はコアメンバーによる紹介制)と、以下に述べます2つの目的の異なる研究会の開催を行っています。<br />
<br />
1つ目は「'''年会'''」と呼ばれる会です。定量的な生命科学研究に携わる・もしくは携わりたいと考えている研究者どうしが集まって相互に情報を発信することで、技術的な問題の解決方法や今後の研究の方向性などを模索することを目指します。<br />
<br />
2つ目は「'''キャラバン'''」と呼ばれる会です。(主に)定量生物学に携わっていないが興味を抱いている研究者に向けて、定量的な生命科学研究の重要性や成果を発信する会です。2009年3月に初回のキャラバンを「遺伝研」で開催しました。今後も、様々な研究機関で開催したいと考えています。<br />
<br />
[https://q-bio.jp/index.php?title=English#Agenda Agenda (English)]<br />
<br />
=== コアメンバー・世話人===<br />
*[[コアメンバー世話人一覧|コアメンバー・世話人の一覧]]<br />
*[http://www.q-bio.jp/wiki/English#Core_members Core members]<br />
<br />
=== 研究会のウェブサイト ===<br />
URL: http://q-bio.jp/<br />
<br><br />
URL (English page): http://q-bio.jp/wiki/English<br />
<br />
=== 研究会の問い合わせ先 ===<br />
連絡先:q.biology at gmail.com<br />
(迷惑メール対策のため@をatと表示しています。at を @ に置換してください)<br />
<br />
== 我々が考える定量生物学 2008 ==<br />
定量的なデータ解析は生命科学の様々な分野において行われており、すべてを本研究会で網羅することは現実的でないと考えています。そこで、あくまで本研究会が対象に設定している定量生物学であることを明示するために、「我々が考える定量生物学」というタイトルにしました。また、「我々が考える定量生物学」も未成熟であり、今後色々な人と議論を交わす過程で変わっていくと思います。変わっていく過程、外部からの意見を取り入れる姿勢を示すという意味で、各年度ごとに定義を更新していくのもおもしろいかと考えました。そのため2008という日付を入れてあります。<br />
<br />
=== なぜ定量生物学が再び注目されてきているのか?===<br />
定量的な生命科学が注目されてきている背景として、イメージングなどの光学技術、MEMSなどの工学技術の発展に伴い、より解像度の高い時空間情報を得られるようになったことが挙げられます。また、実験・解析技術の異分野間交流が進み、それにともなって優れた定量解析から生命システムの原理に迫る研究が分野を超えて認識されるようになってきたことも背景の一つに挙げられます。<br />
<br />
例えば主に分子生物学的手法を用いてきた細胞生物学や発生生物学では、バイオイメージングなどの発展によりこれまで見過ごされてきた、あるいは解析できなかった分子レベル、細胞レベルの現象を詳細に可視化できるようになりました。それにともない、現象を定量的に解析すること、そしてそのための数理、実験手法の必要性が認識されるようになってきました。このような流れは、定量的な解析が分子生物学成立直後までは活発に行われていたことを考えると、ルネッサンス的な意味を持っていると考えられます。<br />
<br />
一方で生物物理学においては、バイオイメージングなどを駆使した定量的な解析は継続的に行われてきましたが、逆にスクリーニングなどの分子生物学的な研究はあまり集中的に行われてきませんでした。しかし最近、生物物理学の方法論と分子生物学の方法論の双方を使いこなす若手研究者が現れ、融合的な研究の機運が高まってきています。また、これまでタンパク質構造などの分子レベルの現象と比較して比重が低かった細胞レベルの現象や個体発生に挑む研究者も増加傾向にあり、細胞や組織のスケールにおける定量的な研究が顕在化してきているという背景もあります。<br />
<br />
さらに、理論系研究においては、利用可能な定量的な実験データが限られていた時代の理論生物学のスタイルから脱却した、定量的な実験データの存在を前提とする現代的な理論生物学が求められています。またインフォマティクスでは、分子生物学の発展に立脚したオミクス情報を対象とした研究だけでなく、オミクス情報ほど網羅的ではないがより定量性の高いデータという新しい種類の情報を対象としたインフォマティクスの可能性を探る試みがなされてきています。<br />
<br />
このように定量生物学は、生命科学の様々な分野における新しい流れが結びついた異分野融合の交差点に位置していると考えられます。そして「定量生物学の会」は、定量的な生命科学に挑戦する様々な分野の若手研究者が、その技術や知見を交換をする場としての役割を担っていきたいと考えています。しかし研究会としては、'''定量的な研究はあくまで手段であって、我々の最終的な目的はこれまで明らかにされていない生命現象の謎を解くことにある'''と考えています。<br />
<br />
[http://www.q-bio.jp/wiki/English#Background_of_the_foundation Background of the foundation (English)]<br />
<br><br />
[http://www.q-bio.jp/wiki/English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 我々が現在想定している定量生物学の研究対象 ===<br />
定量的なデータ解析は生命科学の様々な分野において行われており、そのすべてを本研究会で網羅することは現実的でないと考えています。本研究会が現時点でターゲットとしている研究は、まず過去に定量的な方法論を使っていたにもかかわらず、分子生物学による定性分析の台頭によって、定量的な思考や方法論が衰退してしまった分野です。例えば発生学はこのような分野の1例であると考えられます。このような分野では定量的な思考や手法が遅れている分、それらを導入することにより生命現象の理解が格段に進む可能性があります。<br />
<br />
他方で、生物物理学における細胞ダイナミクスの解析など、定量的な解析手法の適用範囲を多階層のスケールを横断する形で拡張する境界領域分野も主要な対象とします。解析対象は分子から個体までを含みますが、特に細胞・組織の階層を含む研究を中心に据えます。分子、個体においては、それぞれ、より高次・低次の現象との関係を意識したものに積極的に取り組み、分子と分子内部分構造などは重点的には扱いません。<br />
<br />
さらに、理論系研究においてはアイディア・モデルのみに動機づけられた研究よりも、定量的なデータや知見を積極的に取り入れた理論を模索する研究を現時点では想定しています。また、画像データから定量性の高い時空間情報を抽出することが現在の定量生物学におけるデータ生産のボトルネックになっていることから、画像解析を中心としたインフォマティクスの研究も歓迎します。<br />
<br />
神経科学は伝統的に定量性を意識した研究がなされてきた分野でありますが、すでに電気生理データなどの定量的な解析手法が比較的成熟しているため、現時点では対象に含めていません。ただし、神経科学と他分野を定量的な解析手法でつなぐ横断的研究(成長円錐の走性・神経細胞内の1分子計測・神経発生)などは対象に含めます。<br />
<br />
また、マイクロアレイなどの網羅的な解析を中心とした研究も現時点では対象に含めていません。ただし、網羅的な解析を発展させ、高い定量性持たせることを追求するような研究については対象に含めます。<br />
<br />
[http://www.q-bio.jp/wiki/English#Targeting_Subject Trageting Subgect (English)]</div>Noriko.hiroihttp://131.113.63.82/index.php?title=About_us&diff=129206About us2022-09-13T05:59:23Z<p>Noriko.hiroi: /* 背景 */</p>
<hr />
<div>== 定量生物学の会の概要 ==<br />
[[English| go to English page]] <br />
=== 背景 ===<br />
現在、生命科学の多数の領域において、定量的なアプローチを導入した研究が分子生物学を補完する1つの方向性として浮上しつつあり、すでに萌芽的な研究例が報告されています。<br />
<br />
「定量生物学の会」はこのような背景のもと、各領域において自ら手を動かして定量的な生命科学を模索している若手研究者により2回の準備会を経て立ち上げられた研究グループです。<br />
<br />
[https://q-bio.jp/index.php?title=English#Background_of_the_foundation Background of the foundation(English)]<br />
<br />
=== 会の目的 ===<br />
本研究会は定量的な生命科学の方向性・問題点などを具体的に議論し、領域横断的な研究体制や連携関係をトップダウン的にではなく、最前線の研究を担う若手研究者(学生、PD、若手PI)によってボトムアップ的に模索することを目的としています。<br />
<br />
[https://q-bio.jp/index.php?title=English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 会の活動 ===<br />
メーリングリストによる情報交換(参加はコアメンバーによる紹介制)と、以下に述べます2つの目的の異なる研究会の開催を行っています。<br />
<br />
1つ目は「'''年会'''」と呼ばれる会です。定量的な生命科学研究に携わる・もしくは携わりたいと考えている研究者どうしが集まって相互に情報を発信することで、技術的な問題の解決方法や今後の研究の方向性などを模索することを目指します。<br />
<br />
2つ目は「'''キャラバン'''」と呼ばれる会です。(主に)定量生物学に携わっていないが興味を抱いている研究者に向けて、定量的な生命科学研究の重要性や成果を発信する会です。2009年3月に初回のキャラバンを「遺伝研」で開催しました。今後も、様々な研究機関で開催したいと考えています。<br />
<br />
[http://www.q-bio.jp/wiki/English#Agenda Agenda (English)]<br />
<br />
=== コアメンバー・世話人===<br />
*[[コアメンバー世話人一覧|コアメンバー・世話人の一覧]]<br />
*[http://www.q-bio.jp/wiki/English#Core_members Core members]<br />
<br />
=== 研究会のウェブサイト ===<br />
URL: http://q-bio.jp/<br />
<br><br />
URL (English page): http://q-bio.jp/wiki/English<br />
<br />
=== 研究会の問い合わせ先 ===<br />
連絡先:q.biology at gmail.com<br />
(迷惑メール対策のため@をatと表示しています。at を @ に置換してください)<br />
<br />
== 我々が考える定量生物学 2008 ==<br />
定量的なデータ解析は生命科学の様々な分野において行われており、すべてを本研究会で網羅することは現実的でないと考えています。そこで、あくまで本研究会が対象に設定している定量生物学であることを明示するために、「我々が考える定量生物学」というタイトルにしました。また、「我々が考える定量生物学」も未成熟であり、今後色々な人と議論を交わす過程で変わっていくと思います。変わっていく過程、外部からの意見を取り入れる姿勢を示すという意味で、各年度ごとに定義を更新していくのもおもしろいかと考えました。そのため2008という日付を入れてあります。<br />
<br />
=== なぜ定量生物学が再び注目されてきているのか?===<br />
定量的な生命科学が注目されてきている背景として、イメージングなどの光学技術、MEMSなどの工学技術の発展に伴い、より解像度の高い時空間情報を得られるようになったことが挙げられます。また、実験・解析技術の異分野間交流が進み、それにともなって優れた定量解析から生命システムの原理に迫る研究が分野を超えて認識されるようになってきたことも背景の一つに挙げられます。<br />
<br />
例えば主に分子生物学的手法を用いてきた細胞生物学や発生生物学では、バイオイメージングなどの発展によりこれまで見過ごされてきた、あるいは解析できなかった分子レベル、細胞レベルの現象を詳細に可視化できるようになりました。それにともない、現象を定量的に解析すること、そしてそのための数理、実験手法の必要性が認識されるようになってきました。このような流れは、定量的な解析が分子生物学成立直後までは活発に行われていたことを考えると、ルネッサンス的な意味を持っていると考えられます。<br />
<br />
一方で生物物理学においては、バイオイメージングなどを駆使した定量的な解析は継続的に行われてきましたが、逆にスクリーニングなどの分子生物学的な研究はあまり集中的に行われてきませんでした。しかし最近、生物物理学の方法論と分子生物学の方法論の双方を使いこなす若手研究者が現れ、融合的な研究の機運が高まってきています。また、これまでタンパク質構造などの分子レベルの現象と比較して比重が低かった細胞レベルの現象や個体発生に挑む研究者も増加傾向にあり、細胞や組織のスケールにおける定量的な研究が顕在化してきているという背景もあります。<br />
<br />
さらに、理論系研究においては、利用可能な定量的な実験データが限られていた時代の理論生物学のスタイルから脱却した、定量的な実験データの存在を前提とする現代的な理論生物学が求められています。またインフォマティクスでは、分子生物学の発展に立脚したオミクス情報を対象とした研究だけでなく、オミクス情報ほど網羅的ではないがより定量性の高いデータという新しい種類の情報を対象としたインフォマティクスの可能性を探る試みがなされてきています。<br />
<br />
このように定量生物学は、生命科学の様々な分野における新しい流れが結びついた異分野融合の交差点に位置していると考えられます。そして「定量生物学の会」は、定量的な生命科学に挑戦する様々な分野の若手研究者が、その技術や知見を交換をする場としての役割を担っていきたいと考えています。しかし研究会としては、'''定量的な研究はあくまで手段であって、我々の最終的な目的はこれまで明らかにされていない生命現象の謎を解くことにある'''と考えています。<br />
<br />
[http://www.q-bio.jp/wiki/English#Background_of_the_foundation Background of the foundation (English)]<br />
<br><br />
[http://www.q-bio.jp/wiki/English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 我々が現在想定している定量生物学の研究対象 ===<br />
定量的なデータ解析は生命科学の様々な分野において行われており、そのすべてを本研究会で網羅することは現実的でないと考えています。本研究会が現時点でターゲットとしている研究は、まず過去に定量的な方法論を使っていたにもかかわらず、分子生物学による定性分析の台頭によって、定量的な思考や方法論が衰退してしまった分野です。例えば発生学はこのような分野の1例であると考えられます。このような分野では定量的な思考や手法が遅れている分、それらを導入することにより生命現象の理解が格段に進む可能性があります。<br />
<br />
他方で、生物物理学における細胞ダイナミクスの解析など、定量的な解析手法の適用範囲を多階層のスケールを横断する形で拡張する境界領域分野も主要な対象とします。解析対象は分子から個体までを含みますが、特に細胞・組織の階層を含む研究を中心に据えます。分子、個体においては、それぞれ、より高次・低次の現象との関係を意識したものに積極的に取り組み、分子と分子内部分構造などは重点的には扱いません。<br />
<br />
さらに、理論系研究においてはアイディア・モデルのみに動機づけられた研究よりも、定量的なデータや知見を積極的に取り入れた理論を模索する研究を現時点では想定しています。また、画像データから定量性の高い時空間情報を抽出することが現在の定量生物学におけるデータ生産のボトルネックになっていることから、画像解析を中心としたインフォマティクスの研究も歓迎します。<br />
<br />
神経科学は伝統的に定量性を意識した研究がなされてきた分野でありますが、すでに電気生理データなどの定量的な解析手法が比較的成熟しているため、現時点では対象に含めていません。ただし、神経科学と他分野を定量的な解析手法でつなぐ横断的研究(成長円錐の走性・神経細胞内の1分子計測・神経発生)などは対象に含めます。<br />
<br />
また、マイクロアレイなどの網羅的な解析を中心とした研究も現時点では対象に含めていません。ただし、網羅的な解析を発展させ、高い定量性持たせることを追求するような研究については対象に含めます。<br />
<br />
[http://www.q-bio.jp/wiki/English#Targeting_Subject Trageting Subgect (English)]</div>Noriko.hiroihttp://131.113.63.82/index.php?title=About_us&diff=129204About us2022-09-13T05:59:03Z<p>Noriko.hiroi: /* 会の目的 */</p>
<hr />
<div>== 定量生物学の会の概要 ==<br />
[[English| go to English page]] <br />
=== 背景 ===<br />
現在、生命科学の多数の領域において、定量的なアプローチを導入した研究が分子生物学を補完する1つの方向性として浮上しつつあり、すでに萌芽的な研究例が報告されています。<br />
<br />
「定量生物学の会」はこのような背景のもと、各領域において自ら手を動かして定量的な生命科学を模索している若手研究者により2回の準備会を経て立ち上げられた研究グループです。<br />
<br />
[https://q-bio.jp/index.php?title=English#Background_of_the_foundation (English)]<br />
<br />
=== 会の目的 ===<br />
本研究会は定量的な生命科学の方向性・問題点などを具体的に議論し、領域横断的な研究体制や連携関係をトップダウン的にではなく、最前線の研究を担う若手研究者(学生、PD、若手PI)によってボトムアップ的に模索することを目的としています。<br />
<br />
[https://q-bio.jp/index.php?title=English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 会の活動 ===<br />
メーリングリストによる情報交換(参加はコアメンバーによる紹介制)と、以下に述べます2つの目的の異なる研究会の開催を行っています。<br />
<br />
1つ目は「'''年会'''」と呼ばれる会です。定量的な生命科学研究に携わる・もしくは携わりたいと考えている研究者どうしが集まって相互に情報を発信することで、技術的な問題の解決方法や今後の研究の方向性などを模索することを目指します。<br />
<br />
2つ目は「'''キャラバン'''」と呼ばれる会です。(主に)定量生物学に携わっていないが興味を抱いている研究者に向けて、定量的な生命科学研究の重要性や成果を発信する会です。2009年3月に初回のキャラバンを「遺伝研」で開催しました。今後も、様々な研究機関で開催したいと考えています。<br />
<br />
[http://www.q-bio.jp/wiki/English#Agenda Agenda (English)]<br />
<br />
=== コアメンバー・世話人===<br />
*[[コアメンバー世話人一覧|コアメンバー・世話人の一覧]]<br />
*[http://www.q-bio.jp/wiki/English#Core_members Core members]<br />
<br />
=== 研究会のウェブサイト ===<br />
URL: http://q-bio.jp/<br />
<br><br />
URL (English page): http://q-bio.jp/wiki/English<br />
<br />
=== 研究会の問い合わせ先 ===<br />
連絡先:q.biology at gmail.com<br />
(迷惑メール対策のため@をatと表示しています。at を @ に置換してください)<br />
<br />
== 我々が考える定量生物学 2008 ==<br />
定量的なデータ解析は生命科学の様々な分野において行われており、すべてを本研究会で網羅することは現実的でないと考えています。そこで、あくまで本研究会が対象に設定している定量生物学であることを明示するために、「我々が考える定量生物学」というタイトルにしました。また、「我々が考える定量生物学」も未成熟であり、今後色々な人と議論を交わす過程で変わっていくと思います。変わっていく過程、外部からの意見を取り入れる姿勢を示すという意味で、各年度ごとに定義を更新していくのもおもしろいかと考えました。そのため2008という日付を入れてあります。<br />
<br />
=== なぜ定量生物学が再び注目されてきているのか?===<br />
定量的な生命科学が注目されてきている背景として、イメージングなどの光学技術、MEMSなどの工学技術の発展に伴い、より解像度の高い時空間情報を得られるようになったことが挙げられます。また、実験・解析技術の異分野間交流が進み、それにともなって優れた定量解析から生命システムの原理に迫る研究が分野を超えて認識されるようになってきたことも背景の一つに挙げられます。<br />
<br />
例えば主に分子生物学的手法を用いてきた細胞生物学や発生生物学では、バイオイメージングなどの発展によりこれまで見過ごされてきた、あるいは解析できなかった分子レベル、細胞レベルの現象を詳細に可視化できるようになりました。それにともない、現象を定量的に解析すること、そしてそのための数理、実験手法の必要性が認識されるようになってきました。このような流れは、定量的な解析が分子生物学成立直後までは活発に行われていたことを考えると、ルネッサンス的な意味を持っていると考えられます。<br />
<br />
一方で生物物理学においては、バイオイメージングなどを駆使した定量的な解析は継続的に行われてきましたが、逆にスクリーニングなどの分子生物学的な研究はあまり集中的に行われてきませんでした。しかし最近、生物物理学の方法論と分子生物学の方法論の双方を使いこなす若手研究者が現れ、融合的な研究の機運が高まってきています。また、これまでタンパク質構造などの分子レベルの現象と比較して比重が低かった細胞レベルの現象や個体発生に挑む研究者も増加傾向にあり、細胞や組織のスケールにおける定量的な研究が顕在化してきているという背景もあります。<br />
<br />
さらに、理論系研究においては、利用可能な定量的な実験データが限られていた時代の理論生物学のスタイルから脱却した、定量的な実験データの存在を前提とする現代的な理論生物学が求められています。またインフォマティクスでは、分子生物学の発展に立脚したオミクス情報を対象とした研究だけでなく、オミクス情報ほど網羅的ではないがより定量性の高いデータという新しい種類の情報を対象としたインフォマティクスの可能性を探る試みがなされてきています。<br />
<br />
このように定量生物学は、生命科学の様々な分野における新しい流れが結びついた異分野融合の交差点に位置していると考えられます。そして「定量生物学の会」は、定量的な生命科学に挑戦する様々な分野の若手研究者が、その技術や知見を交換をする場としての役割を担っていきたいと考えています。しかし研究会としては、'''定量的な研究はあくまで手段であって、我々の最終的な目的はこれまで明らかにされていない生命現象の謎を解くことにある'''と考えています。<br />
<br />
[http://www.q-bio.jp/wiki/English#Background_of_the_foundation Background of the foundation (English)]<br />
<br><br />
[http://www.q-bio.jp/wiki/English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 我々が現在想定している定量生物学の研究対象 ===<br />
定量的なデータ解析は生命科学の様々な分野において行われており、そのすべてを本研究会で網羅することは現実的でないと考えています。本研究会が現時点でターゲットとしている研究は、まず過去に定量的な方法論を使っていたにもかかわらず、分子生物学による定性分析の台頭によって、定量的な思考や方法論が衰退してしまった分野です。例えば発生学はこのような分野の1例であると考えられます。このような分野では定量的な思考や手法が遅れている分、それらを導入することにより生命現象の理解が格段に進む可能性があります。<br />
<br />
他方で、生物物理学における細胞ダイナミクスの解析など、定量的な解析手法の適用範囲を多階層のスケールを横断する形で拡張する境界領域分野も主要な対象とします。解析対象は分子から個体までを含みますが、特に細胞・組織の階層を含む研究を中心に据えます。分子、個体においては、それぞれ、より高次・低次の現象との関係を意識したものに積極的に取り組み、分子と分子内部分構造などは重点的には扱いません。<br />
<br />
さらに、理論系研究においてはアイディア・モデルのみに動機づけられた研究よりも、定量的なデータや知見を積極的に取り入れた理論を模索する研究を現時点では想定しています。また、画像データから定量性の高い時空間情報を抽出することが現在の定量生物学におけるデータ生産のボトルネックになっていることから、画像解析を中心としたインフォマティクスの研究も歓迎します。<br />
<br />
神経科学は伝統的に定量性を意識した研究がなされてきた分野でありますが、すでに電気生理データなどの定量的な解析手法が比較的成熟しているため、現時点では対象に含めていません。ただし、神経科学と他分野を定量的な解析手法でつなぐ横断的研究(成長円錐の走性・神経細胞内の1分子計測・神経発生)などは対象に含めます。<br />
<br />
また、マイクロアレイなどの網羅的な解析を中心とした研究も現時点では対象に含めていません。ただし、網羅的な解析を発展させ、高い定量性持たせることを追求するような研究については対象に含めます。<br />
<br />
[http://www.q-bio.jp/wiki/English#Targeting_Subject Trageting Subgect (English)]</div>Noriko.hiroihttp://131.113.63.82/index.php?title=About_us&diff=129202About us2022-09-13T05:57:52Z<p>Noriko.hiroi: /* 定量生物学の会の概要 */</p>
<hr />
<div>== 定量生物学の会の概要 ==<br />
[[English| go to English page]] <br />
=== 背景 ===<br />
現在、生命科学の多数の領域において、定量的なアプローチを導入した研究が分子生物学を補完する1つの方向性として浮上しつつあり、すでに萌芽的な研究例が報告されています。<br />
<br />
「定量生物学の会」はこのような背景のもと、各領域において自ら手を動かして定量的な生命科学を模索している若手研究者により2回の準備会を経て立ち上げられた研究グループです。<br />
<br />
[https://q-bio.jp/index.php?title=English#Background_of_the_foundation (English)]<br />
<br />
=== 会の目的 ===<br />
本研究会は定量的な生命科学の方向性・問題点などを具体的に議論し、領域横断的な研究体制や連携関係をトップダウン的にではなく、最前線の研究を担う若手研究者(学生、PD、若手PI)によってボトムアップ的に模索することを目的としています。<br />
<br />
[http://www.q-bio.jp/wiki/English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 会の活動 ===<br />
メーリングリストによる情報交換(参加はコアメンバーによる紹介制)と、以下に述べます2つの目的の異なる研究会の開催を行っています。<br />
<br />
1つ目は「'''年会'''」と呼ばれる会です。定量的な生命科学研究に携わる・もしくは携わりたいと考えている研究者どうしが集まって相互に情報を発信することで、技術的な問題の解決方法や今後の研究の方向性などを模索することを目指します。<br />
<br />
2つ目は「'''キャラバン'''」と呼ばれる会です。(主に)定量生物学に携わっていないが興味を抱いている研究者に向けて、定量的な生命科学研究の重要性や成果を発信する会です。2009年3月に初回のキャラバンを「遺伝研」で開催しました。今後も、様々な研究機関で開催したいと考えています。<br />
<br />
[http://www.q-bio.jp/wiki/English#Agenda Agenda (English)]<br />
<br />
=== コアメンバー・世話人===<br />
*[[コアメンバー世話人一覧|コアメンバー・世話人の一覧]]<br />
*[http://www.q-bio.jp/wiki/English#Core_members Core members]<br />
<br />
=== 研究会のウェブサイト ===<br />
URL: http://q-bio.jp/<br />
<br><br />
URL (English page): http://q-bio.jp/wiki/English<br />
<br />
=== 研究会の問い合わせ先 ===<br />
連絡先:q.biology at gmail.com<br />
(迷惑メール対策のため@をatと表示しています。at を @ に置換してください)<br />
<br />
== 我々が考える定量生物学 2008 ==<br />
定量的なデータ解析は生命科学の様々な分野において行われており、すべてを本研究会で網羅することは現実的でないと考えています。そこで、あくまで本研究会が対象に設定している定量生物学であることを明示するために、「我々が考える定量生物学」というタイトルにしました。また、「我々が考える定量生物学」も未成熟であり、今後色々な人と議論を交わす過程で変わっていくと思います。変わっていく過程、外部からの意見を取り入れる姿勢を示すという意味で、各年度ごとに定義を更新していくのもおもしろいかと考えました。そのため2008という日付を入れてあります。<br />
<br />
=== なぜ定量生物学が再び注目されてきているのか?===<br />
定量的な生命科学が注目されてきている背景として、イメージングなどの光学技術、MEMSなどの工学技術の発展に伴い、より解像度の高い時空間情報を得られるようになったことが挙げられます。また、実験・解析技術の異分野間交流が進み、それにともなって優れた定量解析から生命システムの原理に迫る研究が分野を超えて認識されるようになってきたことも背景の一つに挙げられます。<br />
<br />
例えば主に分子生物学的手法を用いてきた細胞生物学や発生生物学では、バイオイメージングなどの発展によりこれまで見過ごされてきた、あるいは解析できなかった分子レベル、細胞レベルの現象を詳細に可視化できるようになりました。それにともない、現象を定量的に解析すること、そしてそのための数理、実験手法の必要性が認識されるようになってきました。このような流れは、定量的な解析が分子生物学成立直後までは活発に行われていたことを考えると、ルネッサンス的な意味を持っていると考えられます。<br />
<br />
一方で生物物理学においては、バイオイメージングなどを駆使した定量的な解析は継続的に行われてきましたが、逆にスクリーニングなどの分子生物学的な研究はあまり集中的に行われてきませんでした。しかし最近、生物物理学の方法論と分子生物学の方法論の双方を使いこなす若手研究者が現れ、融合的な研究の機運が高まってきています。また、これまでタンパク質構造などの分子レベルの現象と比較して比重が低かった細胞レベルの現象や個体発生に挑む研究者も増加傾向にあり、細胞や組織のスケールにおける定量的な研究が顕在化してきているという背景もあります。<br />
<br />
さらに、理論系研究においては、利用可能な定量的な実験データが限られていた時代の理論生物学のスタイルから脱却した、定量的な実験データの存在を前提とする現代的な理論生物学が求められています。またインフォマティクスでは、分子生物学の発展に立脚したオミクス情報を対象とした研究だけでなく、オミクス情報ほど網羅的ではないがより定量性の高いデータという新しい種類の情報を対象としたインフォマティクスの可能性を探る試みがなされてきています。<br />
<br />
このように定量生物学は、生命科学の様々な分野における新しい流れが結びついた異分野融合の交差点に位置していると考えられます。そして「定量生物学の会」は、定量的な生命科学に挑戦する様々な分野の若手研究者が、その技術や知見を交換をする場としての役割を担っていきたいと考えています。しかし研究会としては、'''定量的な研究はあくまで手段であって、我々の最終的な目的はこれまで明らかにされていない生命現象の謎を解くことにある'''と考えています。<br />
<br />
[http://www.q-bio.jp/wiki/English#Background_of_the_foundation Background of the foundation (English)]<br />
<br><br />
[http://www.q-bio.jp/wiki/English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 我々が現在想定している定量生物学の研究対象 ===<br />
定量的なデータ解析は生命科学の様々な分野において行われており、そのすべてを本研究会で網羅することは現実的でないと考えています。本研究会が現時点でターゲットとしている研究は、まず過去に定量的な方法論を使っていたにもかかわらず、分子生物学による定性分析の台頭によって、定量的な思考や方法論が衰退してしまった分野です。例えば発生学はこのような分野の1例であると考えられます。このような分野では定量的な思考や手法が遅れている分、それらを導入することにより生命現象の理解が格段に進む可能性があります。<br />
<br />
他方で、生物物理学における細胞ダイナミクスの解析など、定量的な解析手法の適用範囲を多階層のスケールを横断する形で拡張する境界領域分野も主要な対象とします。解析対象は分子から個体までを含みますが、特に細胞・組織の階層を含む研究を中心に据えます。分子、個体においては、それぞれ、より高次・低次の現象との関係を意識したものに積極的に取り組み、分子と分子内部分構造などは重点的には扱いません。<br />
<br />
さらに、理論系研究においてはアイディア・モデルのみに動機づけられた研究よりも、定量的なデータや知見を積極的に取り入れた理論を模索する研究を現時点では想定しています。また、画像データから定量性の高い時空間情報を抽出することが現在の定量生物学におけるデータ生産のボトルネックになっていることから、画像解析を中心としたインフォマティクスの研究も歓迎します。<br />
<br />
神経科学は伝統的に定量性を意識した研究がなされてきた分野でありますが、すでに電気生理データなどの定量的な解析手法が比較的成熟しているため、現時点では対象に含めていません。ただし、神経科学と他分野を定量的な解析手法でつなぐ横断的研究(成長円錐の走性・神経細胞内の1分子計測・神経発生)などは対象に含めます。<br />
<br />
また、マイクロアレイなどの網羅的な解析を中心とした研究も現時点では対象に含めていません。ただし、網羅的な解析を発展させ、高い定量性持たせることを追求するような研究については対象に含めます。<br />
<br />
[http://www.q-bio.jp/wiki/English#Targeting_Subject Trageting Subgect (English)]</div>Noriko.hiroihttp://131.113.63.82/index.php?title=About_us&diff=129200About us2022-09-13T05:57:01Z<p>Noriko.hiroi: /* 背景 */</p>
<hr />
<div>== 定量生物学の会の概要 ==<br />
[[English| go to English page]] <br />
=== 背景 ===<br />
現在、生命科学の多数の領域において、定量的なアプローチを導入した研究が分子生物学を補完する1つの方向性として浮上しつつあり、すでに萌芽的な研究例が報告されています。<br />
<br />
「定量生物学の会」はこのような背景のもと、各領域において自ら手を動かして定量的な生命科学を模索している若手研究者により2回の準備会を経て立ち上げられた研究グループです。<br />
<br />
[https://q-bio.jp/index.php?title=English (English)]<br />
<br />
=== 会の目的 ===<br />
本研究会は定量的な生命科学の方向性・問題点などを具体的に議論し、領域横断的な研究体制や連携関係をトップダウン的にではなく、最前線の研究を担う若手研究者(学生、PD、若手PI)によってボトムアップ的に模索することを目的としています。<br />
<br />
[http://www.q-bio.jp/wiki/English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 会の活動 ===<br />
メーリングリストによる情報交換(参加はコアメンバーによる紹介制)と、以下に述べます2つの目的の異なる研究会の開催を行っています。<br />
<br />
1つ目は「'''年会'''」と呼ばれる会です。定量的な生命科学研究に携わる・もしくは携わりたいと考えている研究者どうしが集まって相互に情報を発信することで、技術的な問題の解決方法や今後の研究の方向性などを模索することを目指します。<br />
<br />
2つ目は「'''キャラバン'''」と呼ばれる会です。(主に)定量生物学に携わっていないが興味を抱いている研究者に向けて、定量的な生命科学研究の重要性や成果を発信する会です。2009年3月に初回のキャラバンを「遺伝研」で開催しました。今後も、様々な研究機関で開催したいと考えています。<br />
<br />
[http://www.q-bio.jp/wiki/English#Agenda Agenda (English)]<br />
<br />
=== コアメンバー・世話人===<br />
*[[コアメンバー世話人一覧|コアメンバー・世話人の一覧]]<br />
*[http://www.q-bio.jp/wiki/English#Core_members Core members]<br />
<br />
=== 研究会のウェブサイト ===<br />
URL: http://q-bio.jp/<br />
<br><br />
URL (English page): http://q-bio.jp/wiki/English<br />
<br />
=== 研究会の問い合わせ先 ===<br />
連絡先:q.biology at gmail.com<br />
(迷惑メール対策のため@をatと表示しています。at を @ に置換してください)<br />
<br />
== 我々が考える定量生物学 2008 ==<br />
定量的なデータ解析は生命科学の様々な分野において行われており、すべてを本研究会で網羅することは現実的でないと考えています。そこで、あくまで本研究会が対象に設定している定量生物学であることを明示するために、「我々が考える定量生物学」というタイトルにしました。また、「我々が考える定量生物学」も未成熟であり、今後色々な人と議論を交わす過程で変わっていくと思います。変わっていく過程、外部からの意見を取り入れる姿勢を示すという意味で、各年度ごとに定義を更新していくのもおもしろいかと考えました。そのため2008という日付を入れてあります。<br />
<br />
=== なぜ定量生物学が再び注目されてきているのか?===<br />
定量的な生命科学が注目されてきている背景として、イメージングなどの光学技術、MEMSなどの工学技術の発展に伴い、より解像度の高い時空間情報を得られるようになったことが挙げられます。また、実験・解析技術の異分野間交流が進み、それにともなって優れた定量解析から生命システムの原理に迫る研究が分野を超えて認識されるようになってきたことも背景の一つに挙げられます。<br />
<br />
例えば主に分子生物学的手法を用いてきた細胞生物学や発生生物学では、バイオイメージングなどの発展によりこれまで見過ごされてきた、あるいは解析できなかった分子レベル、細胞レベルの現象を詳細に可視化できるようになりました。それにともない、現象を定量的に解析すること、そしてそのための数理、実験手法の必要性が認識されるようになってきました。このような流れは、定量的な解析が分子生物学成立直後までは活発に行われていたことを考えると、ルネッサンス的な意味を持っていると考えられます。<br />
<br />
一方で生物物理学においては、バイオイメージングなどを駆使した定量的な解析は継続的に行われてきましたが、逆にスクリーニングなどの分子生物学的な研究はあまり集中的に行われてきませんでした。しかし最近、生物物理学の方法論と分子生物学の方法論の双方を使いこなす若手研究者が現れ、融合的な研究の機運が高まってきています。また、これまでタンパク質構造などの分子レベルの現象と比較して比重が低かった細胞レベルの現象や個体発生に挑む研究者も増加傾向にあり、細胞や組織のスケールにおける定量的な研究が顕在化してきているという背景もあります。<br />
<br />
さらに、理論系研究においては、利用可能な定量的な実験データが限られていた時代の理論生物学のスタイルから脱却した、定量的な実験データの存在を前提とする現代的な理論生物学が求められています。またインフォマティクスでは、分子生物学の発展に立脚したオミクス情報を対象とした研究だけでなく、オミクス情報ほど網羅的ではないがより定量性の高いデータという新しい種類の情報を対象としたインフォマティクスの可能性を探る試みがなされてきています。<br />
<br />
このように定量生物学は、生命科学の様々な分野における新しい流れが結びついた異分野融合の交差点に位置していると考えられます。そして「定量生物学の会」は、定量的な生命科学に挑戦する様々な分野の若手研究者が、その技術や知見を交換をする場としての役割を担っていきたいと考えています。しかし研究会としては、'''定量的な研究はあくまで手段であって、我々の最終的な目的はこれまで明らかにされていない生命現象の謎を解くことにある'''と考えています。<br />
<br />
[http://www.q-bio.jp/wiki/English#Background_of_the_foundation Background of the foundation (English)]<br />
<br><br />
[http://www.q-bio.jp/wiki/English#The_Aim_of_the_Q-BioJP The Aim of the Q-BioJP (English)]<br />
<br />
=== 我々が現在想定している定量生物学の研究対象 ===<br />
定量的なデータ解析は生命科学の様々な分野において行われており、そのすべてを本研究会で網羅することは現実的でないと考えています。本研究会が現時点でターゲットとしている研究は、まず過去に定量的な方法論を使っていたにもかかわらず、分子生物学による定性分析の台頭によって、定量的な思考や方法論が衰退してしまった分野です。例えば発生学はこのような分野の1例であると考えられます。このような分野では定量的な思考や手法が遅れている分、それらを導入することにより生命現象の理解が格段に進む可能性があります。<br />
<br />
他方で、生物物理学における細胞ダイナミクスの解析など、定量的な解析手法の適用範囲を多階層のスケールを横断する形で拡張する境界領域分野も主要な対象とします。解析対象は分子から個体までを含みますが、特に細胞・組織の階層を含む研究を中心に据えます。分子、個体においては、それぞれ、より高次・低次の現象との関係を意識したものに積極的に取り組み、分子と分子内部分構造などは重点的には扱いません。<br />
<br />
さらに、理論系研究においてはアイディア・モデルのみに動機づけられた研究よりも、定量的なデータや知見を積極的に取り入れた理論を模索する研究を現時点では想定しています。また、画像データから定量性の高い時空間情報を抽出することが現在の定量生物学におけるデータ生産のボトルネックになっていることから、画像解析を中心としたインフォマティクスの研究も歓迎します。<br />
<br />
神経科学は伝統的に定量性を意識した研究がなされてきた分野でありますが、すでに電気生理データなどの定量的な解析手法が比較的成熟しているため、現時点では対象に含めていません。ただし、神経科学と他分野を定量的な解析手法でつなぐ横断的研究(成長円錐の走性・神経細胞内の1分子計測・神経発生)などは対象に含めます。<br />
<br />
また、マイクロアレイなどの網羅的な解析を中心とした研究も現時点では対象に含めていません。ただし、網羅的な解析を発展させ、高い定量性持たせることを追求するような研究については対象に含めます。<br />
<br />
[http://www.q-bio.jp/wiki/English#Targeting_Subject Trageting Subgect (English)]</div>Noriko.hiroihttp://131.113.63.82/index.php?title=%E3%82%B3%E3%82%A2%E3%83%A1%E3%83%B3%E3%83%90%E3%83%BC%E4%B8%96%E8%A9%B1%E4%BA%BA%E4%B8%80%E8%A6%A7&diff=5814コアメンバー世話人一覧2021-03-31T21:44:51Z<p>Noriko.hiroi: /* 定量生物学の会 コアメンバー一覧 */</p>
<hr />
<div>==定量生物学の会 コアメンバー一覧 ==<br />
発生生物学・細胞生物学・分子生物学・生物物理学・1分子生物学・数理生物学・バイオインフォマティクス・バイオイメージング・生命工学などの、各分野を牽引してゆくポテンシャルと熱意を秘めていると思われる若手研究者が広く集まっています。<br />
<br />
*青木 一洋 (基礎生物学研究所)<br />
*荒田 幸信 (独立行政法人理化学研究所 基幹研究所)<br />
*伊藤 浩史 (九州大学芸術工学府デザイン人間科学コース)<br />
*内田 誠一 (九州大学大学院 システム情報科学研究院)<br />
*奥 寛雅 (群馬大学)<br />
*木村 暁 (国立遺伝学研究所)<br />
*国田 勝行 (奈良先端科学技術大学院大学)<br />
*小林 徹也 (東京大学 生産技術研究所)<br />
*杉村 薫 (京都大学 iCeMS)<br />
*鈴木 誉保 (東京大学 理学系研究科)<br />
*鈴木 団 (大阪大学)<br />
*高木 拓明 (公立大学法人奈良県立医科大学 医学部)<br />
*塚田 祐基 (名古屋大学大学院 理学研究科)<br />
*寺前 順之介 (京都大学)<br />
*二階堂 愛 (独立行政法人理化学研究所)<br />
*野中 茂紀(基礎生物学研究所)<br />
*日比野 佳代 (国立遺伝学研究所)<br />
*平島 剛志(京都大学)<br />
*広井 賀子 (慶應義塾大学)<br />
*舟橋 啓 (慶應義塾大学 理工学部)<br />
*前多 裕介 (九州大学)<br />
*村田 隆(基礎生物学研究所)<br />
<br /><br />
休部中:<br />
*石原 秀至 (東京大学大学院 総合文化研究科)<br />
*笠井 倫志 (京都大学 再生医科学研究所)<br />
*木下 和久 (独立行政法人理化学研究所 基幹研究所)<br />
*木村 啓志 (東海大学 機械工学科)<br />
*澤井 哲 (東京大学大学院 総合文化研究科)<br />
*筒井 秀和 (北陸先端大学)<br />
*原田 崇広<br />
*松林 完 (King’s College London)<br />
<br /><br />
<br />
==定量生物学の会 世話人一覧 ==<br />
*小林 徹也 (東京大学 生産技術研究所)<br />
*杉村 薫 (京都大学 iCeMS)<br />
*高木 拓明 (公立大学法人奈良県立医科大学 医学部)<br />
*舟橋 啓 (慶應義塾大学 理工学部)</div>Noriko.hiroihttp://131.113.63.82/index.php?title=Events&diff=5286Events2017-05-06T10:44:01Z<p>Noriko.hiroi: /* 終了した定量生物学の会のメンバー主催のイベント */</p>
<hr />
<div>== 最新のイベント情報 ==<br />
=== 定量生物学の会主催の公式研究会 ===<br />
* [[Qbio8th_2016|第八回年会ホームページ]]<br />
<br />
== 過去の研究会情報 ==<br />
=== 終了した定量生物学の会主催の研究会 ===<br />
*定量生物学の会 年会<br />
** [[第一回年会|第一回年会(2009/1)]]<br />
** [[第二回年会|第二回年会(2010/1)]]<br />
** [[定量生物学の会 第三回年会 (2010/11)|第三回年会(2010/11)]]<br />
** [[第四回年会|第四回年会(2012/1)]]<br />
***[[4th_Annual_Meeting|4th Annual Meeting (in English)]]<br />
** [[第五回年会|第五回年会(2012/11)]]<br />
***[[5th_Annual_Meeting|5th Annual Meeting (in English)]]<br />
**[[qbio6th_2013|第六回年会]]<br />
***[[qbio6th_2013en|6th annual meeting]]<br><br />
**[[Qbio7th_2014|第七回年会]]<br />
*[[NIG_International_Symposium_2015_JapanQ-Bioweek|NIG INternational Symposium 2015: Japan Q-Bio week – force, information, and dynamics]]<br />
*定量生物学の会キャラバン<br />
** [[第一回キャラバン]] at 遺伝研<br />
*定量生物学の会準備会<br />
** [[第一回定量生物学の会準備会プログラム|第一回準備会]]<br />
** [[第二回定量生物学の会準備会プログラム|第二回準備会]]<br />
* その他の研究会・夏の学校<br />
** [[日本バイオインフォマティクス学会、定量生物学の会 共催夏の学校2009]]<br />
**NGS現場の会・オープンバイオ研究会・生命情報科学若手の会・定量生物学の会4会合同シンポジウム[http://bioinfowakate.org/events/symposium2012 「これからの生命科学を考える」]<br />
**[http://fun.bio.keio.ac.jp/iwqb2012/ International Workshop on Quantitative Biology 2012 (2012/11)]<br />
**[http://fun.bio.keio.ac.jp/iwqb2013/ International Workshop on Quantitative Biology 2013 (2013/11) ]<br />
<br />
=== 終了した定量生物学の会のメンバー主催のイベント ===<br />
*International Workshop on Quantitative Biology 2014 (2014/9) was held at VLSCI in Melbourne, Australia, as one of the workshops of ICSB 2014.<br />
<br />
* 生物数理モデル入門~生物への数理工学的アプローチ~<br />
**小林徹也(東京大学生産技術研究所)<br />
** 12月04日(木)~1月15日(木):木曜日の16:30~18:00<br />
** 東京大学駒場キャンパス1号館106号室<br />
** 詳細は[http://research.crmind.net/2008/11/post-9.php]をご覧ください。<br />
<br />
*北海道大学理学院生命理学専攻および生命科学院 発生進化学特論<br />
**杉村薫(理研)<br />
**2008年10月30日1限目2限目<br />
**1. 個体発生における力学過程の概論 <br />
**2. 上皮形態形成を支える機械的な力の研究ー実験と理論を融合させて生物システムを理解する<br />
<br />
*東京大学 農学生命情報科学特論II(アグリバイオインフォマティクスセミナー)<br />
**舟橋啓、小林徹也<br />
**システムバイオロジーの最前線:定量生物学から計算生物学まで<br />
**10/23(木):15:00-18:45<br />
**農学部2号館2階第1講義室(化1)<br />
**http://www.iu.a.u-tokyo.ac.jp/main_seminar.html<br />
<br />
*4th International Workshop on Quantitative Biology (IWQB2017)<br />
**舟橋啓、広井賀子 with Viji M Draviam; speakers 木村暁、奥寛雅 他<br />
**2017年4月14日, 15日<br />
**慶應義塾大学理工学部マルチメディアルーム, コラボレーティブデザインルーム<br />
**http://fun.bio.keio.ac.jp/icdc/</div>Noriko.hiroihttp://131.113.63.82/index.php?title=Events&diff=5285Events2017-05-06T10:37:29Z<p>Noriko.hiroi: /* 終了した定量生物学の会主催の研究会 */</p>
<hr />
<div>== 最新のイベント情報 ==<br />
=== 定量生物学の会主催の公式研究会 ===<br />
* [[Qbio8th_2016|第八回年会ホームページ]]<br />
<br />
== 過去の研究会情報 ==<br />
=== 終了した定量生物学の会主催の研究会 ===<br />
*定量生物学の会 年会<br />
** [[第一回年会|第一回年会(2009/1)]]<br />
** [[第二回年会|第二回年会(2010/1)]]<br />
** [[定量生物学の会 第三回年会 (2010/11)|第三回年会(2010/11)]]<br />
** [[第四回年会|第四回年会(2012/1)]]<br />
***[[4th_Annual_Meeting|4th Annual Meeting (in English)]]<br />
** [[第五回年会|第五回年会(2012/11)]]<br />
***[[5th_Annual_Meeting|5th Annual Meeting (in English)]]<br />
**[[qbio6th_2013|第六回年会]]<br />
***[[qbio6th_2013en|6th annual meeting]]<br><br />
**[[Qbio7th_2014|第七回年会]]<br />
*[[NIG_International_Symposium_2015_JapanQ-Bioweek|NIG INternational Symposium 2015: Japan Q-Bio week – force, information, and dynamics]]<br />
*定量生物学の会キャラバン<br />
** [[第一回キャラバン]] at 遺伝研<br />
*定量生物学の会準備会<br />
** [[第一回定量生物学の会準備会プログラム|第一回準備会]]<br />
** [[第二回定量生物学の会準備会プログラム|第二回準備会]]<br />
* その他の研究会・夏の学校<br />
** [[日本バイオインフォマティクス学会、定量生物学の会 共催夏の学校2009]]<br />
**NGS現場の会・オープンバイオ研究会・生命情報科学若手の会・定量生物学の会4会合同シンポジウム[http://bioinfowakate.org/events/symposium2012 「これからの生命科学を考える」]<br />
**[http://fun.bio.keio.ac.jp/iwqb2012/ International Workshop on Quantitative Biology 2012 (2012/11)]<br />
**[http://fun.bio.keio.ac.jp/iwqb2013/ International Workshop on Quantitative Biology 2013 (2013/11) ]<br />
<br />
=== 終了した定量生物学の会のメンバー主催のイベント ===<br />
*International Workshop on Quantitative Biology 2014 (2014/9) was held at VLSCI in Melbourne, Australia, as one of the workshops of ICSB 2014.<br />
<br />
* 生物数理モデル入門~生物への数理工学的アプローチ~<br />
**小林徹也(東京大学生産技術研究所)<br />
** 12月04日(木)~1月15日(木):木曜日の16:30~18:00<br />
** 東京大学駒場キャンパス1号館106号室<br />
** 詳細は[http://research.crmind.net/2008/11/post-9.php]をご覧ください。<br />
<br />
*北海道大学理学院生命理学専攻および生命科学院 発生進化学特論<br />
**杉村薫(理研)<br />
**2008年10月30日1限目2限目<br />
**1. 個体発生における力学過程の概論 <br />
**2. 上皮形態形成を支える機械的な力の研究ー実験と理論を融合させて生物システムを理解する<br />
<br />
*東京大学 農学生命情報科学特論II(アグリバイオインフォマティクスセミナー)<br />
**舟橋啓、小林徹也<br />
**システムバイオロジーの最前線:定量生物学から計算生物学まで<br />
**10/23(木):15:00-18:45<br />
**農学部2号館2階第1講義室(化1)<br />
**http://www.iu.a.u-tokyo.ac.jp/main_seminar.html</div>Noriko.hiroihttp://131.113.63.82/index.php?title=Events&diff=5284Events2017-05-06T10:37:02Z<p>Noriko.hiroi: /* 終了した定量生物学の会主催の研究会 */</p>
<hr />
<div>== 最新のイベント情報 ==<br />
=== 定量生物学の会主催の公式研究会 ===<br />
* [[Qbio8th_2016|第八回年会ホームページ]]<br />
<br />
== 過去の研究会情報 ==<br />
=== 終了した定量生物学の会主催の研究会 ===<br />
*定量生物学の会 年会<br />
** [[第一回年会|第一回年会(2009/1)]]<br />
** [[第二回年会|第二回年会(2010/1)]]<br />
** [[定量生物学の会 第三回年会 (2010/11)|第三回年会(2010/11)]]<br />
** [[第四回年会|第四回年会(2012/1)]]<br />
***[[4th_Annual_Meeting|4th Annual Meeting (in English)]]<br />
** [[第五回年会|第五回年会(2012/11)]]<br />
***[[5th_Annual_Meeting|5th Annual Meeting (in English)]]<br />
**[[qbio6th_2013|第六回年会]]<br />
***[[qbio6th_2013en|6th annual meeting]]<br><br />
**[[Qbio7th_2014|第七回年会]]<br />
*[[NIG_International_Symposium_2015_JapanQ-Bioweek|NIG INternational Symposium 2015: Japan Q-Bio week – force, information, and dynamics]]<br />
*定量生物学の会キャラバン<br />
** [[第一回キャラバン]] at 遺伝研<br />
*定量生物学の会準備会<br />
** [[第一回定量生物学の会準備会プログラム|第一回準備会]]<br />
** [[第二回定量生物学の会準備会プログラム|第二回準備会]]<br />
* その他の研究会・夏の学校<br />
** [[日本バイオインフォマティクス学会、定量生物学の会 共催夏の学校2009]]<br />
**NGS現場の会・オープンバイオ研究会・生命情報科学若手の会・定量生物学の会4会合同シンポジウム[http://bioinfowakate.org/events/symposium2012 「これからの生命科学を考える」]<br />
**[http://fun.bio.keio.ac.jp/iwqb2012/ International Workshop on Quantitative Biology 2012 (2012/11)]<br />
**[http://fun.bio.keio.ac.jp/iwqb2013/ International Workshop on Quantitative Biology 2013 (2013/11) ]<br />
**[http://fun.bio.keio.ac.jp/icdc/ 4th International Workshop on Quantitative Biology (IWQB2017) ]<br />
<br />
=== 終了した定量生物学の会のメンバー主催のイベント ===<br />
*International Workshop on Quantitative Biology 2014 (2014/9) was held at VLSCI in Melbourne, Australia, as one of the workshops of ICSB 2014.<br />
<br />
* 生物数理モデル入門~生物への数理工学的アプローチ~<br />
**小林徹也(東京大学生産技術研究所)<br />
** 12月04日(木)~1月15日(木):木曜日の16:30~18:00<br />
** 東京大学駒場キャンパス1号館106号室<br />
** 詳細は[http://research.crmind.net/2008/11/post-9.php]をご覧ください。<br />
<br />
*北海道大学理学院生命理学専攻および生命科学院 発生進化学特論<br />
**杉村薫(理研)<br />
**2008年10月30日1限目2限目<br />
**1. 個体発生における力学過程の概論 <br />
**2. 上皮形態形成を支える機械的な力の研究ー実験と理論を融合させて生物システムを理解する<br />
<br />
*東京大学 農学生命情報科学特論II(アグリバイオインフォマティクスセミナー)<br />
**舟橋啓、小林徹也<br />
**システムバイオロジーの最前線:定量生物学から計算生物学まで<br />
**10/23(木):15:00-18:45<br />
**農学部2号館2階第1講義室(化1)<br />
**http://www.iu.a.u-tokyo.ac.jp/main_seminar.html</div>Noriko.hiroihttp://131.113.63.82/index.php?title=Events&diff=5283Events2017-05-06T10:35:57Z<p>Noriko.hiroi: /* 定量生物学の会のメンバー主催のイベント */</p>
<hr />
<div>== 最新のイベント情報 ==<br />
=== 定量生物学の会主催の公式研究会 ===<br />
* [[Qbio8th_2016|第八回年会ホームページ]]<br />
<br />
== 過去の研究会情報 ==<br />
=== 終了した定量生物学の会主催の研究会 ===<br />
*定量生物学の会 年会<br />
** [[第一回年会|第一回年会(2009/1)]]<br />
** [[第二回年会|第二回年会(2010/1)]]<br />
** [[定量生物学の会 第三回年会 (2010/11)|第三回年会(2010/11)]]<br />
** [[第四回年会|第四回年会(2012/1)]]<br />
***[[4th_Annual_Meeting|4th Annual Meeting (in English)]]<br />
** [[第五回年会|第五回年会(2012/11)]]<br />
***[[5th_Annual_Meeting|5th Annual Meeting (in English)]]<br />
**[[qbio6th_2013|第六回年会]]<br />
***[[qbio6th_2013en|6th annual meeting]]<br><br />
**[[Qbio7th_2014|第七回年会]]<br />
*[[NIG_International_Symposium_2015_JapanQ-Bioweek|NIG INternational Symposium 2015: Japan Q-Bio week – force, information, and dynamics]]<br />
*定量生物学の会キャラバン<br />
** [[第一回キャラバン]] at 遺伝研<br />
*定量生物学の会準備会<br />
** [[第一回定量生物学の会準備会プログラム|第一回準備会]]<br />
** [[第二回定量生物学の会準備会プログラム|第二回準備会]]<br />
* その他の研究会・夏の学校<br />
** [[日本バイオインフォマティクス学会、定量生物学の会 共催夏の学校2009]]<br />
**NGS現場の会・オープンバイオ研究会・生命情報科学若手の会・定量生物学の会4会合同シンポジウム[http://bioinfowakate.org/events/symposium2012 「これからの生命科学を考える」]<br />
**[http://fun.bio.keio.ac.jp/iwqb2012/ International Workshop on Quantitative Biology 2012 (2012/11)]<br />
**[http://fun.bio.keio.ac.jp/iwqb2013/ International Workshop on Quantitative Biology 2013 (2013/11) ]<br />
<br />
=== 終了した定量生物学の会のメンバー主催のイベント ===<br />
*International Workshop on Quantitative Biology 2014 (2014/9) was held at VLSCI in Melbourne, Australia, as one of the workshops of ICSB 2014.<br />
<br />
* 生物数理モデル入門~生物への数理工学的アプローチ~<br />
**小林徹也(東京大学生産技術研究所)<br />
** 12月04日(木)~1月15日(木):木曜日の16:30~18:00<br />
** 東京大学駒場キャンパス1号館106号室<br />
** 詳細は[http://research.crmind.net/2008/11/post-9.php]をご覧ください。<br />
<br />
*北海道大学理学院生命理学専攻および生命科学院 発生進化学特論<br />
**杉村薫(理研)<br />
**2008年10月30日1限目2限目<br />
**1. 個体発生における力学過程の概論 <br />
**2. 上皮形態形成を支える機械的な力の研究ー実験と理論を融合させて生物システムを理解する<br />
<br />
*東京大学 農学生命情報科学特論II(アグリバイオインフォマティクスセミナー)<br />
**舟橋啓、小林徹也<br />
**システムバイオロジーの最前線:定量生物学から計算生物学まで<br />
**10/23(木):15:00-18:45<br />
**農学部2号館2階第1講義室(化1)<br />
**http://www.iu.a.u-tokyo.ac.jp/main_seminar.html</div>Noriko.hiroihttp://131.113.63.82/index.php?title=News&diff=5282News2017-03-14T13:16:03Z<p>Noriko.hiroi: /* New!! 4th International Workshop on Quantitative Biology (IWQB2017) Registration Open */</p>
<hr />
<div>== News ==<br />
定量生物学に関わる研究者間の情報交換を促進するために、新しく <span style="color: #ff00ff">News page</span> を設けました。<br />
<br />
=== 情報掲載に関する問い合わせ先 ===<br />
当ページへの情報の掲載を希望される方は、ご所属、連絡先、掲載内容及びいつまでに情報を掲載してほしいかを明記の上、下記メールアドレスまでご連絡頂きますようよろしくお願い致します。世話人が掲載手続きを進めさせて頂きます。尚、定量生物学の会のメンバーでなくても情報の掲載を受け付けますので、ぜひ積極的にご活用下さい。<br><br />
<br />
連絡先:q.biology at gmail.com<br />
(迷惑メール対策のため@をatと表示しています。at を @ に置換してください)<br />
<br />
=== 研究費などのお知らせ ===<br />
<br />
==== これまでに掲載したお知らせ====<br />
* JST戦略的創造研究推進事業(CREST、さきがけ)平成27年度研究提案の募集(第1期)について<br />
*JST戦略的創造研究推進事業(CREST、さきがけ)平成27年度CREST・さきがけ研究提案募集(第1期)の予告及び説明会の開催について<br />
* CREST「生命動態」領域 H26年度領域説明会の御案内<br />
*「統合データベース講習会」受入れ機関募集のお知らせ<br />
*ライフサイエンスデータベース統合推進事業「統合データ解析トライアル」平成25年度研究開発提案募集<br />
* 戦略的創造研究推進事業 (CREST、さきがけ) 平成25年度研究提案の募集開始 <br />
*独立行政法人科学技術振興機構(JST) 平成25年度CREST・さきがけ研究提案募集説明会のご案内<br />
<br />
=== 研究会やセミナー,特別講義などのお知らせ ===<br />
<br />
==== <span style="color: red">New!! </span>4th International Workshop on Quantitative Biology (IWQB2017) Registration Open====<br />
<br />
4th International Workshop on Quantitative Biology (IWQB2017)を, 慶應矢上キャンパス(最寄駅: 東横線日吉, 横浜市)で開催します.<br />
<br />
みなさんのご参加をお待ちして居ります.<br />
<br />
Home http://fun.bio.keio.ac.jp/icdc/<br />
<br />
Registration(参加無料) http://fun.bio.keio.ac.jp/icdc/registration/<br />
<br />
日時: 2017年4月14日(金)~ 15日(土)<br />
<br />
場所: 慶応義塾大学理工学部 <br />
14棟マルチメディアルーム及び34棟コラボレーティブデザインルーム<br />
<br />
言語: 英語<br />
<br />
ポスターセッション, ショートトークあります. 国際会議での口頭発表の機会に!<br />
<br />
参加費: 無料<br />
<br />
参加申し込み・演題提出: ホームページより事前申し込み<br />
http://fun.bio.keio.ac.jp/icdc/registration/<br />
<br />
参加登録にはwebの登録フォームを, 要旨提出にはリンクのテンプレートをご利用下さい.<br />
<br />
締め切り: 要旨集 2017年3月31日 (金)<br />
<br />
参加 2017年4月14日 (金)<br />
<br />
<br />
内容・概要:<br />
細胞の運命決定プロセスはダイナミックな過程を経て行われます. その定量的な観察には, 優れた時空間解像度のイメージング技術, またこれまで見出されてこなかった切り口からの新しい撮像条件の作り方, そのための技術発展などが必要です.<br />
IWQB2017では, (i)新しいデータ取得とその解析方法, (ii)ハイスループットイメージングの自動化, (iii)細胞の運命決定過程の解析, (iv)イメージングにおける新技術などに焦点を当て, 講演者の先生方とともに議論をしていきたいと思います.<br />
<br />
ポスター発表, ショートトークの場も設けております.<br />
トピックスとしては以下のものを予定しております.<br />
<br />
Advances in Image analysis methods/Automation of big-data-experiments/Cell division mechanisms/Cytoskeletal regulation/Emerging microscopy tools/Novel fluorescent probes<br />
<br />
参加に費用はかかりません. <br />
皆様のご出席をお待ちしております.<br />
<br />
Address: 慶応義塾大学理工学部14-516 IWQB2017事務局<br />
<br />
Phone: 045-566-1584<br />
<br />
E-mail: icdca14_at_gmail.com<br />
<br />
==== <span style="color: red">New!! </span>CDBシンポジウム2017参加者募集中!====<br />
<br />
テーマ: Towards Understanding Human Development, Heredity, and Evolution<br />
<br />
日時: 2017年3月27日(月)~29日(水)<br />
<br />
場所: 理化学研究所 多細胞システム形成研究センター(兵庫県神戸市ポートアイランド)<br />
<br />
言語: 英語<br />
<br />
参加費: 無料(希望者のみ昼食代、懇親会費別途)<br />
<br />
昼食代: 3,000円(3日間)<br />
<br />
懇親会費: 一般5,000円/学生1,000円<br />
<br />
参加申し込み・演題提出: ホームページより事前申し込み<br />
<br />
締め切り: 2016年12月9日(金)<br />
<br />
URL:http://www.cdb.riken.jp/sympo2017/index.html <br />
<br />
内容・概要:<br />
ヒトをはじめとする霊長類の発生機構は、多くの制約のため理解が遅れていましたが、近年、ES細胞やiPS細胞をはじめとした幹細胞培養技術が著しく進展し、加えて、ライブイメージング、単一細胞トランススクリプトーム等のシングルセルアプローチの開発、ゲノム解析、ゲノム編集技術が急速に発達したことにより、ヒトの生殖系列や初期発生、器官形成の解析に多様なアプローチが可能になり、またこれらのプロセスをin vitroで再構成し、組織や器官を再生しようとする試みもより現実のものとなりつつあります。他方、霊長類がヒトに進化する過程に関しても、化石人類のゲノム解析が可能になり、iPS細胞を利用した遺伝子発現調節や組織形成の種間比較が進んだ結果、常識を覆す新しい発見が続々と報告されています。本シンポジウムはこれらトピックを総合的に検討し、将来の展望を議論する、正に時期を得たものと確信します。<br />
<br />
トピックスとしては以下のものを予定しております。<br />
<br />
(1) Germline/Early embryogenesis、(2) Epigenetics/Chromatic regulation、(3) Organogenesis from hPSCs/hSCs/Disease models、(4) Human Genetics/Evolution<br />
<br />
本会を活発な情報交換の場とするため、一般参加者によるポスター発表を募集しており、優秀な演題には口頭発表をお願いする予定です。また、海外からの参加者(大学院生、研究員)を対象としたTravel Fellowshipを用意し、国内外からの多数の参加をお待ちいたしております。 <br />
是非ご参加ください。<br />
<br />
連絡先:<br />
CDBシンポジウム2017事務局<br />
<br />
国立研究開発法人 理化学研究所 多細胞システム形成研究センター<br />
学術集会担当<br />
<br />
〒650-0047 神戸市中央区港島南町2-2-3<br />
<br />
TEL: 078-306-3010 / FAX: 078-306-3090<br />
<br />
E-mail: sympo2017@cdb.riken.jp<br />
<br />
==== <span style="color: red">New!! </span>第28回CDBミーティング “Cilia and Centrosomes: Current Advances and Future Directions”開催のご案内====<br />
<br />
主催団体名: 理化学研究所 多細胞システム形成研究センター(CDB)<br />
<br />
オーガナイザー: 吉川 雅英(東京大学)、松崎 文雄(理化学研究所CDB)<br />
<br />
・文部科学省科学研究費補助金 新学術領域研究(研究領域提案型)「シリア・中心体系による生体情報フローの制御」<br />
<br />
日時: 2016年11月27日(日)~29日(火)<br />
<br />
場所: 理化学研究所 多細胞システム形成研究センター(兵庫県神戸市ポートアイランド)<br />
<br />
参加費: 無料 *昼食(11/27)希望者は1,000円、懇親会(11/28)希望者は3,000円が別途要<br />
<br />
参加申込・演題提出: 全員ホームページより事前申込要<br />
<br />
締切: 2016年9月30日(金)<br />
<br />
URL:http://www.cdb.riken.jp/cilia/2016/index.html<br />
<br />
シリア-中心体系は様々な生化学シグナルや力学的シグナルの発生・伝達・応答に重要な役割を果たします。とりわけ、一次シリアは驚くほど多様な生理作用に関与し,その破綻は多彩な疾患・症状に結びつく事が爆発的なスピードで明らかにされつつあります。これまで、中心体は細胞分裂における役割から研究され,一方シリアは運動性やシグナル受容という働きに注目されて来ました。本会議の目的は、中心体とシリアという密接に関連する2つの細胞内小器官を、ダイナミックに変化する1つの細胞内小器官と捉え、その構造・形成機構・機能についての情報交換を行うことのできる場を提供することです。これまでシリア-中心体に関する研究をリードして来た海外・国内の研究者を交えて、活発な議論が行われることを期待します。本会議では、一般参加者によるポスター発表を募り、優秀な演題には口頭発表をお願いする予定です。使用言語は英語です。同時通訳はございませんので予めご了承ください。国内外からの多数のご参加をお待ちしております。<br />
<br />
連絡先:CDBミーティング事務局<br />
<br />
理化学研究所 多細胞システム形成研究センター 多細胞システム形成研究推進室内、学術集会担当<br />
<br />
〒650-0047 神戸市中央区港島南町2-2-3<br />
<br />
E-mail: cilia2016@cdb.riken.jp<br />
<br />
==== <span style="color: red">New!! </span>The 28th CDB Meeting “Cilia and Centrosomes: Current Advances and Future Directions” Call for Application and Abstract Submission!====<br />
<br />
We are pleased to announce that the 28th CDB Meeting will be held as follows:<br />
<br />
Title: The 28th CDB Meeting “Cilia and Centrosomes: Current Advances and Future Directions”<br />
<br />
Date: November 27 (Sun.) – 29 (Tue.), 2016<br />
<br />
Venue: RIKEN Center for Developmental Biology, Kobe, Japan<br />
<br />
Application and Abstract submission deadline: Friday, September 30, 2016 (Japan time)<br />
<br />
Participation fee: Free<br />
<br />
Lunch fee (Nov. 28, Optional): 1,000 JPY<br />
Banquet fee (Nov. 27, Optional): 3,000 JPY<br />
<br />
URL: http://www.cdb.riken.jp/cilia/2016/index.html<br />
<br />
Cilia form an apparatus that plays critical roles in the transmission of cell-to- cell signals and motility. The centrosome is a key organelle in mitosis; both cilia and the centrosome are constructed by the same complex: the centriole (basal body). In this MEXT-Cilia Club-CDB joint symposium, we seek to coordinate exchanges on cutting-edge research by prominent international scientists and the achievements of the MEXT group over a 5-year period, and to promote discussion of future directions in studies on cilia and centrosomes. The program will include both oral and poster sessions. A small number of poster abstracts will be selected by the organizing committee for oral presentations. We would be delighted to have your participation at the 28th CDB Meeting.<br />
<br />
Sincerely,<br />
<br />
Masahide Kikkawa (The University of Tokyo, Japan)<br />
<br />
Fumio Matsuzaki (RIKEN CDB, Japan)<br />
<br />
This meeting is co-hosted by cilia club and Grant-in- aid for Scientific Research on Innovative Areas Ministry of Education, Culture, Sports, Science and Technology (MEXT) “Cilium-centrosome system regulating biosignal flows&quot;.<br />
<br />
-- -- -- -- -- -- -- -- -- -- -- -- --<br />
<br />
Contact:<br />
<br />
CDB Meeting Office<br />
<br />
RIKEN Center for Developmental Biology (CDB)<br />
<br />
Office for Research Communications<br />
<br />
2-2- 3, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan<br />
<br />
E-MAIL:cilia2016@cdb.riken.jp<br />
<br />
==== <span style="color: red">New!! </span>第27回CDBミーティング Body Surface Tactics: Cellular crosstalk for the generation of super-biointerfaces のお知らせ====<br />
<br />
【開催日】<br />
2016年11月14日(月)、15日(火)<br />
<br />
【開催地】<br />
理化学研究所 多細胞システム形成研究センター (RIKEN CDB)<br />
<br />
【URL】<br />
http://www.cdb.riken.jp/skin2016/<br />
<br />
【参加・演題〆切】 <br />
2016年9月9日(金)<br />
<br />
【参加費】<br />
無料(希望者のみ昼食代、懇親会費別途)<br />
・昼食代 2,000円(2日間)<br />
・懇親会費 一般5,000円/学生1,000円一般:4,000円<br />
<br />
【言語】<br />
英語<br />
<br />
【基調講演】<br />
Yann Barrandon (École Polytechnique Fédérale de Lausanne, Switzerland)<br />
Cheng-Ming Chuong (University of Southern California, USA)<br />
<br />
【概要】<br />
本会議では、体表を「数ある器官の一つ」として見るのではなく、生命体と環境との境界をなす「スーパーバイオインターフェース」として捉え、体表を構成す る多種多様な細胞の間の相互作用が、多機能性と多様性を兼ね備えた器官のマクロな構造や機能を創発的に生み出す「体表戦略」について議論いたします。会議 での議論を通して、生命の体表戦略の本質的理解に迫るとともに、これまで治療法が確立されて来なかった難治性皮膚疾患の克服や、皮膚の完全再生に向けた戦 略についての新たな洞察が得られることを期待しております。<br />
<br />
トピックスとしては以下のものを予定しております。<br />
(1) Epithelial formation<br />
(2) Functional unit formation<br />
(3) Maintenance and regeneration<br />
(4) Evo-devo<br />
(5) New technologies<br />
(6) Dysfunction and therapeutics<br />
<br />
組織間の相互作用を横糸に、生物種間の多様性を縦糸にすることで、これまで繋がることが少なかった学問分野間の融合的な議論を誘発し、新たな視点で体表の高次機能と機能発現の理解を目指します。<br />
<br />
本会を活発な情報交換の場とするため、一般参加者によるポスター発表を募り、複数の演題には口頭発表をお願いする予定です。若手研究者や大学院生を含む、国内外からの多数のご応募をお待ちいたしております。<br />
<br />
【お問い合わせ】<br />
CDBミーティング事務局 <br />
多細胞システム形成研究センター 研究推進室内<br />
〒650-0047神戸市中央区港島南町2-2-3<br />
E-mail: skin2016@cdb.riken.jp<br />
<br />
==== <span style="color: red">New!! </span>The 27th CDB Meeting. Body Surface Tactics: Cellular crosstalk for the generation of super-biointerfaces ====<br />
<br />
【Date】<br />
November 14 (Mon), 15 (Tue), 2016<br />
<br />
【Venue】 <br />
RIKEN Center for Developmental Biology (CDB), Kobe, Japan<br />
<br />
【URL】<br />
http://www.cdb.riken.jp/skin2016/<br />
<br />
【Deadline for registration and abstract submission】<br />
September 9 (Fri), 2016<br />
<br />
【Participation Fee】<br />
FREE (Lunch and Banquet fee required separately - optional)<br />
Lunch: 2,000 JPY (2 days)<br />
Banquet: 5,000 JPY (General) / 1,000 JPY (Student)<br />
<br />
【Language】<br />
English<br />
<br />
【Keynote Speakers】<br />
Yann Barrandon (École Polytechnique Fédérale de Lausanne, Switzerland)<br />
Cheng-Ming Chuong (University of Southern California, USA)<br />
<br />
【Outline】<br />
The purpose of this meeting is to bring together scientists who are studying the body surface, or skin, in different disciplines, including cell and developmental biology, regenerative biology, vascular and neurobiology, immunology, evolution, mathematics and medicine, to decode the tactics adopted by the body surface to generate an organism’s super-biointerface.<br />
<br />
Topics to be discussed will include<br />
(1) epithelial formation<br />
(2) functional unit formation<br />
(3) maintenance and regeneration<br />
(4) evo-devo<br />
(5) new technologies<br />
(6) dysfunction and therapeutics.<br />
<br />
The program will include both oral and poster sessions. We encourage the submission of abstracts for the poster session from scientists in various fields to increase opportunities for lively and exciting discussion. Several abstracts will be selected for oral presentations.<br />
<br />
We look forward to welcoming you to Kobe and the RIKEN Center for Developmental Biology.<br />
<br />
【Contact】<br />
CDB Meeting Office<br />
RIKEN Center for Developmental Biology<br />
2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan<br />
E-mail: skin2016@cdb.riken.jp<br />
<br />
====これまでに掲載したお知らせ====<br />
*CDBシンポジウム2016/CDB Symposium 2016 参加者募集中!<br />
*第26回CDBミーティング Mechanistic Perspectives of Multicellular Organization開催のご案内<br />
* CDBシンポジウム2015案内<br />
* 2015年度「統合データベース講習会」受入れ機関募集<br />
* バイオイメージデータ解析の公開講座のご案内<br />
* 数理生物学サマーレクチャーコース第2回~データ解析入門~」のお知らせ <br />
* 京都大学生命科学研究科特別講義のお知らせ <br />
* 光イメージング若手研究会「光塾」のお知らせ<br />
<br />
=== 求人情報のお知らせ ===<br />
<br />
==== <span style="color: red">New!! </span> 京大「大規模脳神経3次元回路抽出から計算論的神経科学へ」研究員募集 ==== <br />
京都大学 大学院情報学研究科 論理生命学分野では博士研究員を募集しております。<br />
<br />
(1)CREST「光の特性を活用した生命機能の時空間制御技術の開発と応用」<br />
大規模脳画像から3次元神経回路の抽出を行い、神経回路シミュレーションにより記憶にかかわる神経回路メカニズムを解明することを目的としたプロジェクトにご参加いただける方を募集いたします。当プロジェクトでは、第一に東京大学医学部河西研究室と共同で神経画像を取得し、3次元画像処理により神経回路の抽出を試みます。したがって、[1]三次元画像処理、[2]神経回路シミュレーション、[3]神経生理/分子生物学のうち、[1]を専門とされる方で[2]や[3]に挑戦したい方、あるいは[2]や[3]を専門とされる方で[1]に一定のスキルを有される方を希望いたします。非常に野心的、かつ最先端の研究に挑まれる気概のある方の募集をお待ちしております!<br />
<br />
(2)「人工知能・脳神経系シミュレーション」<br />
人工知能・脳神経系シミュレーション・ハイパフォーマンスコンピューティング、あるいは関連分野に専門性を持つかたのご応募をお待ちいたしております。スーパーコンピューターを用いたハイパフォーマンス・コンピューティングによる脳神経系大規模画像データの処理、あるいは人の脳の柔軟な機能を模倣する脳型人工知能の計算機実装を対象とし、創造力と協調性を持って研究を進めていただける方を希望いたします。<br />
<br />
皆様の身の回りに適任者がおられましたらぜひ声をおかけください!<br />
<br />
●プロジェクト:<br />
(1)平成28年度~33年度 戦略的創造研究推進事業(CREST)<br />
研究領域:「光の特性を活用した生命機能の時空間制御技術の開発と応用」<br />
河西春郎 代表「記憶構造を解明する新しい光操作・画像法の開発」<br />
http://www.jst.go.jp/kisoken/crest/news/2016/160916/160916.html<br />
<br />
(2)文部科学省「ポスト「京」で重点的に取り組むべき社会的・科学的課題に関するアプリケーション開発・研究開発」萌芽的課題<br />
「脳のビッグデータ解析、全脳シミュレーションと脳型人工知能アーキテクチャ」<br />
(沖縄科学技術大学院大学、京都大学、理化学研究所、電気通信大学、東京大学の共同プロジェクト)<br />
<br />
平成28年10月1日から平成30年3月31日まで(調査研究・準備研究フェイズ)<br />
プロジェクトの審査により、さらに、<br />
平成30年4月1日から平成32年3月31日まで(本格実施フェイズ)<br />
<br />
●給与:<br />
京都大学特定研究員の規定によります。<br />
(年俸制。年俸は経験、職務などを考慮決定)<br />
詳細は担当までお問い合わせ下さい。<br />
<br />
●勤務形態:<br />
常勤(任期あり)<br />
裁量労働制で週38時間45分相当<br />
任期1年、更新可(最長上記プロジェクト完了まで)<br />
<br />
●人数:若干名<br />
<br />
●着任時期;<br />
プロジェクト1:平成29年4月1日<br />
プロジェクト2:平成28年11月1日以降のなるべく早い時期<br />
ただし、着任時期については相談にのりますのでお申し出ください。<br />
<br />
●ご応募方法:<br />
・履歴書(写真貼り付け、電子メールアドレスを明記)<br />
・研究業績リスト<br />
・主要論文のコピー(最大3件程度まで、各一部)<br />
・これまでの研究の要約(A4用紙1枚~2枚程度)<br />
プロジェクト1:プロジェクトに関係するスキル・実績に関する自己アピールを含めてください。<br />
プロジェクト2:プログラミングやソフトウェア開発のスキル・実績に関する自己アピールを含めてください。<br />
<br />
・応募者についての意見を伺える方1~2名のご氏名と連絡先<br />
以上を電子ファイルの形で添付したE-mailを<br />
kanae [at] sys.i.kyoto-u.ac.jpまでお送りください。<br />
<br />
もしくは、郵送にてのご応募を希望される方は<br />
石井 信 〒606-8501京都市左京区吉田本町36-1工学部1号館421号室<br />
まで博士研究員応募書類在中と明記した封筒をお送りください。<br />
<br />
●お問い合わせ:<br />
kanae [at] sys.i.kyoto-u.ac.jp<br />
までお気軽にお問合せください。<br />
<br />
●募集期間と選考方法:<br />
募集期間は ** 平成28年12月18日 ** とします。<br />
書類選考のうえ、面接により選考を行います。詳細は別途連絡したします。<br />
適任者が決まり次第、募集を終了いたします。<br />
<br />
==============<br />
<br />
当研究室には、平成28年4月現在、<br />
石井 信(数理工学)<br />
大羽成征(バイオインフォマティクス、統計科学)<br />
前田新一(情報理論、機械学習)、<br />
浦久保秀俊 (計算神経科学)<br />
近藤洋平(数理生物学)<br />
ヘンリク・スキッべ(画像情報学)<br />
中江 健(統計科学、計算神経科学)<br />
村上 陽平(システム生物学)<br />
川瀬貴士(生物画像処理)<br />
メシギ・クーロシ(画像工学、人工知能)<br />
トーステン・ブルマン(計算神経科学)<br />
の各研究者が在籍し、数理工学から脳神経科学、システム生物学、ブレインマシンインターフェースなどへの融合領域への研究展開を、沖縄科学技術大学院 (OIST)、ATR認知機構研究所、理化学研究所脳科 学総合研究センターなどの研究機関との連携の下で実施しております。<br />
<br />
研究室のホームページ<br />
http://ishiilab.jp<br />
京都大学情報学研究科システム科学専攻のホームページ<br />
http://www.sys.i.kyoto-u.ac.jp/index.html<br />
<br />
<br />
==== <span style="color: red">New!! </span> 国立研究開発法人理化学研究所、統合生命医科学研究センターオミクス研究ラボ 研究員または特別研究員 公募 ==== <br />
募集職種:研究員または特別研究員 1名<br />
<br />
職務内容:細胞生物学的手法、分子生物学的手法、免疫学的手法、シークエンス技術、光学顕微鏡、マイクロチップ技術、Bioinformaticsなどを基にして、単一細胞や少数<br />
細胞、組織を対象にした(各種免疫系細胞、腸内細菌など)新しい定量計測法の<br />
開発を行います。また、開発した方法を用いて、医科学的に重要な試料を測定<br />
し、新しい切り口でサイエンスや医科学に貢献することを目指します。<br />
<br />
勤務地:独立行政法人理化学研究所 統合生命医科学研究センター 神奈川県横浜市鶴見区末広町1-7-22<br />
<br />
着任時期:応相談<br />
<br />
研究内容についての問合せ先:<br />
国立研究開発法人理化学研究所統合生命医科学研究センター<br />
オミクス研究ラボ 城口克之<br />
E-mail: katsuyuki.shiroguchi [at]riken.jp ※[at]は@に置き換えてくだ<br />
さい。<br />
<br />
公募の詳細:<br />
http://www.riken.jp/careers/researchers/20150909/<br />
<br />
==== <span style="color: red">New!! </span>Seeking Research Scientist or Postdoctoral Researcher, Laboratory for Quantitative Omics, RIKEN Center for Integrative Medical Sciences====<br />
<br />
Available Positions: Research Scientist or Postdoctoral Researcher, one person, full-time.<br />
<br />
Job Descriptions: A successful candidate will develop new method(s) to measure parameters quantitatively from single cells, a few cells, or cells from tissues (immunological cells, microbiome, etc) based on techniques of cell<br />
biology, molecular biology, immunology, sequencing, optical microscope,<br />
microchip, and/or bioinfomatics. Using the developed method(s), she/he<br />
will measure cells which are medically significant, and intend to contribute to science and medical science from a novel point of view.<br />
<br />
Work location: RIKEN Center for Integrative Medical Sciences. 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045 Japan<br />
<br />
Start of Employment: Negotiable<br />
<br />
Inquiries for research contents<br />
Laboratory for Quantitative Omics, RIKEN Center for Integrative Medical<br />
Sciences<br />
Katsuyuki Shiroguchi<br />
Email: katsuyuki.shiroguchi[at]riken.jp<br />
<br />
Details:http://www.riken.jp/en/careers/researchers/20150909/<br />
<br />
====これまでに掲載したお知らせ====<br />
*明治大学理工学部石原研究室・生命現象の数理モデリングと理論解析を行う博士研究員の公募<br />
*ヘルシンキ大学研究員募集 (20141010)<br />
*JST・ERATO 佐藤ライブ予測制御プロジェクト研究員募集<br />
*JST CRESTプロジェクト「細胞間接着・骨格の秩序形成メカニズムの解明と上皮バリア操作技術の開発」研究員募集<br />
*京大情・論理生命学研・研究員募集<br />
*独立行政法人理化学研究所、統合生命医科学研究センター統合ゲノミクスグループ 研究員または特別研究員の公募<br />
*自然科学研究機構新分野創成センター特任研究員の公募 <br />
*沖縄科学技術大学院大学学園(OIST)バイオインフォマティシャンの求人の募集 <br />
*「生命動態の理解と制御のための基盤技術の創出」研究領域の「時間情報コードによる細胞制御システムの解明」(代表者:黒田真也(東京大学))研究員の募集 <br />
*自然科学研究機構新分野創成センター特任助教等の公募<br />
*東京大学黒田研 特任助教募集募集<br />
*Biology/Genetics/Evolution Postdoctoral Fellow Position, Fred Hutchinson Cancer Research Center (091006)</div>Noriko.hiroihttp://131.113.63.82/index.php?title=Events&diff=5281Events2017-03-14T03:35:11Z<p>Noriko.hiroi: /* 定量生物学の会のメンバー主催のイベント */</p>
<hr />
<div>== 最新のイベント情報 ==<br />
=== 定量生物学の会主催の公式研究会 ===<br />
* [[Qbio8th_2016|第八回年会ホームページ]]<br />
<br />
=== 定量生物学の会のメンバー主催のイベント ===<br />
*[http://fun.bio.keio.ac.jp/icdc/ 4th International Workshop on Quantitative Biology (IWQB2017) ]<br />
<br />
== 過去の研究会情報 ==<br />
=== 終了した定量生物学の会主催の研究会 ===<br />
*定量生物学の会 年会<br />
** [[第一回年会|第一回年会(2009/1)]]<br />
** [[第二回年会|第二回年会(2010/1)]]<br />
** [[定量生物学の会 第三回年会 (2010/11)|第三回年会(2010/11)]]<br />
** [[第四回年会|第四回年会(2012/1)]]<br />
***[[4th_Annual_Meeting|4th Annual Meeting (in English)]]<br />
** [[第五回年会|第五回年会(2012/11)]]<br />
***[[5th_Annual_Meeting|5th Annual Meeting (in English)]]<br />
**[[qbio6th_2013|第六回年会]]<br />
***[[qbio6th_2013en|6th annual meeting]]<br><br />
**[[Qbio7th_2014|第七回年会]]<br />
*[[NIG_International_Symposium_2015_JapanQ-Bioweek|NIG INternational Symposium 2015: Japan Q-Bio week – force, information, and dynamics]]<br />
*定量生物学の会キャラバン<br />
** [[第一回キャラバン]] at 遺伝研<br />
*定量生物学の会準備会<br />
** [[第一回定量生物学の会準備会プログラム|第一回準備会]]<br />
** [[第二回定量生物学の会準備会プログラム|第二回準備会]]<br />
* その他の研究会・夏の学校<br />
** [[日本バイオインフォマティクス学会、定量生物学の会 共催夏の学校2009]]<br />
**NGS現場の会・オープンバイオ研究会・生命情報科学若手の会・定量生物学の会4会合同シンポジウム[http://bioinfowakate.org/events/symposium2012 「これからの生命科学を考える」]<br />
**[http://fun.bio.keio.ac.jp/iwqb2012/ International Workshop on Quantitative Biology 2012 (2012/11)]<br />
**[http://fun.bio.keio.ac.jp/iwqb2013/ International Workshop on Quantitative Biology 2013 (2013/11) ]<br />
<br />
=== 終了した定量生物学の会のメンバー主催のイベント ===<br />
*International Workshop on Quantitative Biology 2014 (2014/9) was held at VLSCI in Melbourne, Australia, as one of the workshops of ICSB 2014.<br />
<br />
* 生物数理モデル入門~生物への数理工学的アプローチ~<br />
**小林徹也(東京大学生産技術研究所)<br />
** 12月04日(木)~1月15日(木):木曜日の16:30~18:00<br />
** 東京大学駒場キャンパス1号館106号室<br />
** 詳細は[http://research.crmind.net/2008/11/post-9.php]をご覧ください。<br />
<br />
*北海道大学理学院生命理学専攻および生命科学院 発生進化学特論<br />
**杉村薫(理研)<br />
**2008年10月30日1限目2限目<br />
**1. 個体発生における力学過程の概論 <br />
**2. 上皮形態形成を支える機械的な力の研究ー実験と理論を融合させて生物システムを理解する<br />
<br />
*東京大学 農学生命情報科学特論II(アグリバイオインフォマティクスセミナー)<br />
**舟橋啓、小林徹也<br />
**システムバイオロジーの最前線:定量生物学から計算生物学まで<br />
**10/23(木):15:00-18:45<br />
**農学部2号館2階第1講義室(化1)<br />
**http://www.iu.a.u-tokyo.ac.jp/main_seminar.html</div>Noriko.hiroihttp://131.113.63.82/index.php?title=Events&diff=5280Events2017-03-14T03:35:02Z<p>Noriko.hiroi: /* 定量生物学の会のメンバー主催のイベント */</p>
<hr />
<div>== 最新のイベント情報 ==<br />
=== 定量生物学の会主催の公式研究会 ===<br />
* [[Qbio8th_2016|第八回年会ホームページ]]<br />
<br />
=== 定量生物学の会のメンバー主催のイベント ===<br />
**[http://fun.bio.keio.ac.jp/icdc/ 4th International Workshop on Quantitative Biology (IWQB2017) ]<br />
<br />
== 過去の研究会情報 ==<br />
=== 終了した定量生物学の会主催の研究会 ===<br />
*定量生物学の会 年会<br />
** [[第一回年会|第一回年会(2009/1)]]<br />
** [[第二回年会|第二回年会(2010/1)]]<br />
** [[定量生物学の会 第三回年会 (2010/11)|第三回年会(2010/11)]]<br />
** [[第四回年会|第四回年会(2012/1)]]<br />
***[[4th_Annual_Meeting|4th Annual Meeting (in English)]]<br />
** [[第五回年会|第五回年会(2012/11)]]<br />
***[[5th_Annual_Meeting|5th Annual Meeting (in English)]]<br />
**[[qbio6th_2013|第六回年会]]<br />
***[[qbio6th_2013en|6th annual meeting]]<br><br />
**[[Qbio7th_2014|第七回年会]]<br />
*[[NIG_International_Symposium_2015_JapanQ-Bioweek|NIG INternational Symposium 2015: Japan Q-Bio week – force, information, and dynamics]]<br />
*定量生物学の会キャラバン<br />
** [[第一回キャラバン]] at 遺伝研<br />
*定量生物学の会準備会<br />
** [[第一回定量生物学の会準備会プログラム|第一回準備会]]<br />
** [[第二回定量生物学の会準備会プログラム|第二回準備会]]<br />
* その他の研究会・夏の学校<br />
** [[日本バイオインフォマティクス学会、定量生物学の会 共催夏の学校2009]]<br />
**NGS現場の会・オープンバイオ研究会・生命情報科学若手の会・定量生物学の会4会合同シンポジウム[http://bioinfowakate.org/events/symposium2012 「これからの生命科学を考える」]<br />
**[http://fun.bio.keio.ac.jp/iwqb2012/ International Workshop on Quantitative Biology 2012 (2012/11)]<br />
**[http://fun.bio.keio.ac.jp/iwqb2013/ International Workshop on Quantitative Biology 2013 (2013/11) ]<br />
<br />
=== 終了した定量生物学の会のメンバー主催のイベント ===<br />
*International Workshop on Quantitative Biology 2014 (2014/9) was held at VLSCI in Melbourne, Australia, as one of the workshops of ICSB 2014.<br />
<br />
* 生物数理モデル入門~生物への数理工学的アプローチ~<br />
**小林徹也(東京大学生産技術研究所)<br />
** 12月04日(木)~1月15日(木):木曜日の16:30~18:00<br />
** 東京大学駒場キャンパス1号館106号室<br />
** 詳細は[http://research.crmind.net/2008/11/post-9.php]をご覧ください。<br />
<br />
*北海道大学理学院生命理学専攻および生命科学院 発生進化学特論<br />
**杉村薫(理研)<br />
**2008年10月30日1限目2限目<br />
**1. 個体発生における力学過程の概論 <br />
**2. 上皮形態形成を支える機械的な力の研究ー実験と理論を融合させて生物システムを理解する<br />
<br />
*東京大学 農学生命情報科学特論II(アグリバイオインフォマティクスセミナー)<br />
**舟橋啓、小林徹也<br />
**システムバイオロジーの最前線:定量生物学から計算生物学まで<br />
**10/23(木):15:00-18:45<br />
**農学部2号館2階第1講義室(化1)<br />
**http://www.iu.a.u-tokyo.ac.jp/main_seminar.html</div>Noriko.hiroihttp://131.113.63.82/index.php?title=News&diff=5279News2017-03-14T03:33:03Z<p>Noriko.hiroi: /* 研究会やセミナー,特別講義などのお知らせ */</p>
<hr />
<div>== News ==<br />
定量生物学に関わる研究者間の情報交換を促進するために、新しく <span style="color: #ff00ff">News page</span> を設けました。<br />
<br />
=== 情報掲載に関する問い合わせ先 ===<br />
当ページへの情報の掲載を希望される方は、ご所属、連絡先、掲載内容及びいつまでに情報を掲載してほしいかを明記の上、下記メールアドレスまでご連絡頂きますようよろしくお願い致します。世話人が掲載手続きを進めさせて頂きます。尚、定量生物学の会のメンバーでなくても情報の掲載を受け付けますので、ぜひ積極的にご活用下さい。<br><br />
<br />
連絡先:q.biology at gmail.com<br />
(迷惑メール対策のため@をatと表示しています。at を @ に置換してください)<br />
<br />
=== 研究費などのお知らせ ===<br />
<br />
==== これまでに掲載したお知らせ====<br />
* JST戦略的創造研究推進事業(CREST、さきがけ)平成27年度研究提案の募集(第1期)について<br />
*JST戦略的創造研究推進事業(CREST、さきがけ)平成27年度CREST・さきがけ研究提案募集(第1期)の予告及び説明会の開催について<br />
* CREST「生命動態」領域 H26年度領域説明会の御案内<br />
*「統合データベース講習会」受入れ機関募集のお知らせ<br />
*ライフサイエンスデータベース統合推進事業「統合データ解析トライアル」平成25年度研究開発提案募集<br />
* 戦略的創造研究推進事業 (CREST、さきがけ) 平成25年度研究提案の募集開始 <br />
*独立行政法人科学技術振興機構(JST) 平成25年度CREST・さきがけ研究提案募集説明会のご案内<br />
<br />
=== 研究会やセミナー,特別講義などのお知らせ ===<br />
<br />
==== <span style="color: red">New!! </span>4th International Workshop on Quantitative Biology (IWQB2017) Registration Open====<br />
<br />
4th International Workshop on Quantitative Biology (IWQB2017)を, 慶應矢上キャンパス(最寄駅: 東横線日吉, 横浜市)で開催します.<br />
<br />
みなさんのご参加をお待ちして居ります.<br />
<br />
Home http://fun.bio.keio.ac.jp/icdc/<br />
<br />
Registration(参加無料) http://fun.bio.keio.ac.jp/icdc/registration/<br />
<br />
日時: 2017年4月14日(金)~ 15日(土)<br />
<br />
場所: 慶応義塾大学理工学部 <br />
14棟マルチメディアルーム及び34棟コラボレーティブデザインルーム<br />
<br />
言語: 英語<br />
<br />
ポスターセッション, ショートトークあります. 国際会議での口頭発表の機会に!<br />
<br />
参加費: 無料<br />
<br />
参加申し込み・演題提出: ホームページより事前申し込み<br />
http://fun.bio.keio.ac.jp/icdc/registration/<br />
<br />
参加登録にはwebの登録フォームを, 要旨提出にはリンクのテンプレートをご利用下さい.<br />
<br />
締め切り: 要旨集 2017年3月31日 (金)<br />
<br />
参加 2017年4月14日 (金)<br />
<br />
<br />
内容・概要:<br />
細胞の運命決定プロセスはダイナミックな過程を経て行われます. 定量的な観察には, 優れた時空間解像度のイメージング技術, またこれまで見出されてこなかった切り口からの新しい撮像条件の作り方, そのための技術発展などが必要です.<br />
IWQB2017では, (i)新しいデータ取得とその解析方法, (ii)ハイスループットイメージングの自動化, (iii)細胞の運命決定過程の解析, (iv)イメージングにおける新技術などに焦点を当て, 講演者の先生方とともに議論をしていきたいと思います.<br />
<br />
ポスター発表, ショートトークの場も設けております.<br />
トピックスとしては以下のものを予定しております.<br />
<br />
Advances in Image analysis methods/Automation of big-data-experiments/Cell division mechanisms/Cytoskeletal regulation/Emerging microscopy tools/Novel fluorescent probes<br />
<br />
参加に費用はかかりません. <br />
皆様のご出席をお待ちしております.<br />
<br />
Address: 慶応義塾大学理工学部14-516 IWQB2017事務局<br />
<br />
Phone: 045-566-1584<br />
<br />
E-mail: icdca14_at_gmail.com<br />
<br />
<br />
==== <span style="color: red">New!! </span>CDBシンポジウム2017参加者募集中!====<br />
<br />
テーマ: Towards Understanding Human Development, Heredity, and Evolution<br />
<br />
日時: 2017年3月27日(月)~29日(水)<br />
<br />
場所: 理化学研究所 多細胞システム形成研究センター(兵庫県神戸市ポートアイランド)<br />
<br />
言語: 英語<br />
<br />
参加費: 無料(希望者のみ昼食代、懇親会費別途)<br />
<br />
昼食代: 3,000円(3日間)<br />
<br />
懇親会費: 一般5,000円/学生1,000円<br />
<br />
参加申し込み・演題提出: ホームページより事前申し込み<br />
<br />
締め切り: 2016年12月9日(金)<br />
<br />
URL:http://www.cdb.riken.jp/sympo2017/index.html <br />
<br />
内容・概要:<br />
ヒトをはじめとする霊長類の発生機構は、多くの制約のため理解が遅れていましたが、近年、ES細胞やiPS細胞をはじめとした幹細胞培養技術が著しく進展し、加えて、ライブイメージング、単一細胞トランススクリプトーム等のシングルセルアプローチの開発、ゲノム解析、ゲノム編集技術が急速に発達したことにより、ヒトの生殖系列や初期発生、器官形成の解析に多様なアプローチが可能になり、またこれらのプロセスをin vitroで再構成し、組織や器官を再生しようとする試みもより現実のものとなりつつあります。他方、霊長類がヒトに進化する過程に関しても、化石人類のゲノム解析が可能になり、iPS細胞を利用した遺伝子発現調節や組織形成の種間比較が進んだ結果、常識を覆す新しい発見が続々と報告されています。本シンポジウムはこれらトピックを総合的に検討し、将来の展望を議論する、正に時期を得たものと確信します。<br />
<br />
トピックスとしては以下のものを予定しております。<br />
<br />
(1) Germline/Early embryogenesis、(2) Epigenetics/Chromatic regulation、(3) Organogenesis from hPSCs/hSCs/Disease models、(4) Human Genetics/Evolution<br />
<br />
本会を活発な情報交換の場とするため、一般参加者によるポスター発表を募集しており、優秀な演題には口頭発表をお願いする予定です。また、海外からの参加者(大学院生、研究員)を対象としたTravel Fellowshipを用意し、国内外からの多数の参加をお待ちいたしております。 <br />
是非ご参加ください。<br />
<br />
連絡先:<br />
CDBシンポジウム2017事務局<br />
<br />
国立研究開発法人 理化学研究所 多細胞システム形成研究センター<br />
学術集会担当<br />
<br />
〒650-0047 神戸市中央区港島南町2-2-3<br />
<br />
TEL: 078-306-3010 / FAX: 078-306-3090<br />
<br />
E-mail: sympo2017@cdb.riken.jp<br />
<br />
==== <span style="color: red">New!! </span>第28回CDBミーティング “Cilia and Centrosomes: Current Advances and Future Directions”開催のご案内====<br />
<br />
主催団体名: 理化学研究所 多細胞システム形成研究センター(CDB)<br />
<br />
オーガナイザー: 吉川 雅英(東京大学)、松崎 文雄(理化学研究所CDB)<br />
<br />
・文部科学省科学研究費補助金 新学術領域研究(研究領域提案型)「シリア・中心体系による生体情報フローの制御」<br />
<br />
日時: 2016年11月27日(日)~29日(火)<br />
<br />
場所: 理化学研究所 多細胞システム形成研究センター(兵庫県神戸市ポートアイランド)<br />
<br />
参加費: 無料 *昼食(11/27)希望者は1,000円、懇親会(11/28)希望者は3,000円が別途要<br />
<br />
参加申込・演題提出: 全員ホームページより事前申込要<br />
<br />
締切: 2016年9月30日(金)<br />
<br />
URL:http://www.cdb.riken.jp/cilia/2016/index.html<br />
<br />
シリア-中心体系は様々な生化学シグナルや力学的シグナルの発生・伝達・応答に重要な役割を果たします。とりわけ、一次シリアは驚くほど多様な生理作用に関与し,その破綻は多彩な疾患・症状に結びつく事が爆発的なスピードで明らかにされつつあります。これまで、中心体は細胞分裂における役割から研究され,一方シリアは運動性やシグナル受容という働きに注目されて来ました。本会議の目的は、中心体とシリアという密接に関連する2つの細胞内小器官を、ダイナミックに変化する1つの細胞内小器官と捉え、その構造・形成機構・機能についての情報交換を行うことのできる場を提供することです。これまでシリア-中心体に関する研究をリードして来た海外・国内の研究者を交えて、活発な議論が行われることを期待します。本会議では、一般参加者によるポスター発表を募り、優秀な演題には口頭発表をお願いする予定です。使用言語は英語です。同時通訳はございませんので予めご了承ください。国内外からの多数のご参加をお待ちしております。<br />
<br />
連絡先:CDBミーティング事務局<br />
<br />
理化学研究所 多細胞システム形成研究センター 多細胞システム形成研究推進室内、学術集会担当<br />
<br />
〒650-0047 神戸市中央区港島南町2-2-3<br />
<br />
E-mail: cilia2016@cdb.riken.jp<br />
<br />
==== <span style="color: red">New!! </span>The 28th CDB Meeting “Cilia and Centrosomes: Current Advances and Future Directions” Call for Application and Abstract Submission!====<br />
<br />
We are pleased to announce that the 28th CDB Meeting will be held as follows:<br />
<br />
Title: The 28th CDB Meeting “Cilia and Centrosomes: Current Advances and Future Directions”<br />
<br />
Date: November 27 (Sun.) – 29 (Tue.), 2016<br />
<br />
Venue: RIKEN Center for Developmental Biology, Kobe, Japan<br />
<br />
Application and Abstract submission deadline: Friday, September 30, 2016 (Japan time)<br />
<br />
Participation fee: Free<br />
<br />
Lunch fee (Nov. 28, Optional): 1,000 JPY<br />
Banquet fee (Nov. 27, Optional): 3,000 JPY<br />
<br />
URL: http://www.cdb.riken.jp/cilia/2016/index.html<br />
<br />
Cilia form an apparatus that plays critical roles in the transmission of cell-to- cell signals and motility. The centrosome is a key organelle in mitosis; both cilia and the centrosome are constructed by the same complex: the centriole (basal body). In this MEXT-Cilia Club-CDB joint symposium, we seek to coordinate exchanges on cutting-edge research by prominent international scientists and the achievements of the MEXT group over a 5-year period, and to promote discussion of future directions in studies on cilia and centrosomes. The program will include both oral and poster sessions. A small number of poster abstracts will be selected by the organizing committee for oral presentations. We would be delighted to have your participation at the 28th CDB Meeting.<br />
<br />
Sincerely,<br />
<br />
Masahide Kikkawa (The University of Tokyo, Japan)<br />
<br />
Fumio Matsuzaki (RIKEN CDB, Japan)<br />
<br />
This meeting is co-hosted by cilia club and Grant-in- aid for Scientific Research on Innovative Areas Ministry of Education, Culture, Sports, Science and Technology (MEXT) “Cilium-centrosome system regulating biosignal flows&quot;.<br />
<br />
-- -- -- -- -- -- -- -- -- -- -- -- --<br />
<br />
Contact:<br />
<br />
CDB Meeting Office<br />
<br />
RIKEN Center for Developmental Biology (CDB)<br />
<br />
Office for Research Communications<br />
<br />
2-2- 3, Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan<br />
<br />
E-MAIL:cilia2016@cdb.riken.jp<br />
<br />
==== <span style="color: red">New!! </span>第27回CDBミーティング Body Surface Tactics: Cellular crosstalk for the generation of super-biointerfaces のお知らせ====<br />
<br />
【開催日】<br />
2016年11月14日(月)、15日(火)<br />
<br />
【開催地】<br />
理化学研究所 多細胞システム形成研究センター (RIKEN CDB)<br />
<br />
【URL】<br />
http://www.cdb.riken.jp/skin2016/<br />
<br />
【参加・演題〆切】 <br />
2016年9月9日(金)<br />
<br />
【参加費】<br />
無料(希望者のみ昼食代、懇親会費別途)<br />
・昼食代 2,000円(2日間)<br />
・懇親会費 一般5,000円/学生1,000円一般:4,000円<br />
<br />
【言語】<br />
英語<br />
<br />
【基調講演】<br />
Yann Barrandon (École Polytechnique Fédérale de Lausanne, Switzerland)<br />
Cheng-Ming Chuong (University of Southern California, USA)<br />
<br />
【概要】<br />
本会議では、体表を「数ある器官の一つ」として見るのではなく、生命体と環境との境界をなす「スーパーバイオインターフェース」として捉え、体表を構成す る多種多様な細胞の間の相互作用が、多機能性と多様性を兼ね備えた器官のマクロな構造や機能を創発的に生み出す「体表戦略」について議論いたします。会議 での議論を通して、生命の体表戦略の本質的理解に迫るとともに、これまで治療法が確立されて来なかった難治性皮膚疾患の克服や、皮膚の完全再生に向けた戦 略についての新たな洞察が得られることを期待しております。<br />
<br />
トピックスとしては以下のものを予定しております。<br />
(1) Epithelial formation<br />
(2) Functional unit formation<br />
(3) Maintenance and regeneration<br />
(4) Evo-devo<br />
(5) New technologies<br />
(6) Dysfunction and therapeutics<br />
<br />
組織間の相互作用を横糸に、生物種間の多様性を縦糸にすることで、これまで繋がることが少なかった学問分野間の融合的な議論を誘発し、新たな視点で体表の高次機能と機能発現の理解を目指します。<br />
<br />
本会を活発な情報交換の場とするため、一般参加者によるポスター発表を募り、複数の演題には口頭発表をお願いする予定です。若手研究者や大学院生を含む、国内外からの多数のご応募をお待ちいたしております。<br />
<br />
【お問い合わせ】<br />
CDBミーティング事務局 <br />
多細胞システム形成研究センター 研究推進室内<br />
〒650-0047神戸市中央区港島南町2-2-3<br />
E-mail: skin2016@cdb.riken.jp<br />
<br />
==== <span style="color: red">New!! </span>The 27th CDB Meeting. Body Surface Tactics: Cellular crosstalk for the generation of super-biointerfaces ====<br />
<br />
【Date】<br />
November 14 (Mon), 15 (Tue), 2016<br />
<br />
【Venue】 <br />
RIKEN Center for Developmental Biology (CDB), Kobe, Japan<br />
<br />
【URL】<br />
http://www.cdb.riken.jp/skin2016/<br />
<br />
【Deadline for registration and abstract submission】<br />
September 9 (Fri), 2016<br />
<br />
【Participation Fee】<br />
FREE (Lunch and Banquet fee required separately - optional)<br />
Lunch: 2,000 JPY (2 days)<br />
Banquet: 5,000 JPY (General) / 1,000 JPY (Student)<br />
<br />
【Language】<br />
English<br />
<br />
【Keynote Speakers】<br />
Yann Barrandon (École Polytechnique Fédérale de Lausanne, Switzerland)<br />
Cheng-Ming Chuong (University of Southern California, USA)<br />
<br />
【Outline】<br />
The purpose of this meeting is to bring together scientists who are studying the body surface, or skin, in different disciplines, including cell and developmental biology, regenerative biology, vascular and neurobiology, immunology, evolution, mathematics and medicine, to decode the tactics adopted by the body surface to generate an organism’s super-biointerface.<br />
<br />
Topics to be discussed will include<br />
(1) epithelial formation<br />
(2) functional unit formation<br />
(3) maintenance and regeneration<br />
(4) evo-devo<br />
(5) new technologies<br />
(6) dysfunction and therapeutics.<br />
<br />
The program will include both oral and poster sessions. We encourage the submission of abstracts for the poster session from scientists in various fields to increase opportunities for lively and exciting discussion. Several abstracts will be selected for oral presentations.<br />
<br />
We look forward to welcoming you to Kobe and the RIKEN Center for Developmental Biology.<br />
<br />
【Contact】<br />
CDB Meeting Office<br />
RIKEN Center for Developmental Biology<br />
2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan<br />
E-mail: skin2016@cdb.riken.jp<br />
<br />
====これまでに掲載したお知らせ====<br />
*CDBシンポジウム2016/CDB Symposium 2016 参加者募集中!<br />
*第26回CDBミーティング Mechanistic Perspectives of Multicellular Organization開催のご案内<br />
* CDBシンポジウム2015案内<br />
* 2015年度「統合データベース講習会」受入れ機関募集<br />
* バイオイメージデータ解析の公開講座のご案内<br />
* 数理生物学サマーレクチャーコース第2回~データ解析入門~」のお知らせ <br />
* 京都大学生命科学研究科特別講義のお知らせ <br />
* 光イメージング若手研究会「光塾」のお知らせ<br />
<br />
=== 求人情報のお知らせ ===<br />
<br />
==== <span style="color: red">New!! </span> 京大「大規模脳神経3次元回路抽出から計算論的神経科学へ」研究員募集 ==== <br />
京都大学 大学院情報学研究科 論理生命学分野では博士研究員を募集しております。<br />
<br />
(1)CREST「光の特性を活用した生命機能の時空間制御技術の開発と応用」<br />
大規模脳画像から3次元神経回路の抽出を行い、神経回路シミュレーションにより記憶にかかわる神経回路メカニズムを解明することを目的としたプロジェクトにご参加いただける方を募集いたします。当プロジェクトでは、第一に東京大学医学部河西研究室と共同で神経画像を取得し、3次元画像処理により神経回路の抽出を試みます。したがって、[1]三次元画像処理、[2]神経回路シミュレーション、[3]神経生理/分子生物学のうち、[1]を専門とされる方で[2]や[3]に挑戦したい方、あるいは[2]や[3]を専門とされる方で[1]に一定のスキルを有される方を希望いたします。非常に野心的、かつ最先端の研究に挑まれる気概のある方の募集をお待ちしております!<br />
<br />
(2)「人工知能・脳神経系シミュレーション」<br />
人工知能・脳神経系シミュレーション・ハイパフォーマンスコンピューティング、あるいは関連分野に専門性を持つかたのご応募をお待ちいたしております。スーパーコンピューターを用いたハイパフォーマンス・コンピューティングによる脳神経系大規模画像データの処理、あるいは人の脳の柔軟な機能を模倣する脳型人工知能の計算機実装を対象とし、創造力と協調性を持って研究を進めていただける方を希望いたします。<br />
<br />
皆様の身の回りに適任者がおられましたらぜひ声をおかけください!<br />
<br />
●プロジェクト:<br />
(1)平成28年度~33年度 戦略的創造研究推進事業(CREST)<br />
研究領域:「光の特性を活用した生命機能の時空間制御技術の開発と応用」<br />
河西春郎 代表「記憶構造を解明する新しい光操作・画像法の開発」<br />
http://www.jst.go.jp/kisoken/crest/news/2016/160916/160916.html<br />
<br />
(2)文部科学省「ポスト「京」で重点的に取り組むべき社会的・科学的課題に関するアプリケーション開発・研究開発」萌芽的課題<br />
「脳のビッグデータ解析、全脳シミュレーションと脳型人工知能アーキテクチャ」<br />
(沖縄科学技術大学院大学、京都大学、理化学研究所、電気通信大学、東京大学の共同プロジェクト)<br />
<br />
平成28年10月1日から平成30年3月31日まで(調査研究・準備研究フェイズ)<br />
プロジェクトの審査により、さらに、<br />
平成30年4月1日から平成32年3月31日まで(本格実施フェイズ)<br />
<br />
●給与:<br />
京都大学特定研究員の規定によります。<br />
(年俸制。年俸は経験、職務などを考慮決定)<br />
詳細は担当までお問い合わせ下さい。<br />
<br />
●勤務形態:<br />
常勤(任期あり)<br />
裁量労働制で週38時間45分相当<br />
任期1年、更新可(最長上記プロジェクト完了まで)<br />
<br />
●人数:若干名<br />
<br />
●着任時期;<br />
プロジェクト1:平成29年4月1日<br />
プロジェクト2:平成28年11月1日以降のなるべく早い時期<br />
ただし、着任時期については相談にのりますのでお申し出ください。<br />
<br />
●ご応募方法:<br />
・履歴書(写真貼り付け、電子メールアドレスを明記)<br />
・研究業績リスト<br />
・主要論文のコピー(最大3件程度まで、各一部)<br />
・これまでの研究の要約(A4用紙1枚~2枚程度)<br />
プロジェクト1:プロジェクトに関係するスキル・実績に関する自己アピールを含めてください。<br />
プロジェクト2:プログラミングやソフトウェア開発のスキル・実績に関する自己アピールを含めてください。<br />
<br />
・応募者についての意見を伺える方1~2名のご氏名と連絡先<br />
以上を電子ファイルの形で添付したE-mailを<br />
kanae [at] sys.i.kyoto-u.ac.jpまでお送りください。<br />
<br />
もしくは、郵送にてのご応募を希望される方は<br />
石井 信 〒606-8501京都市左京区吉田本町36-1工学部1号館421号室<br />
まで博士研究員応募書類在中と明記した封筒をお送りください。<br />
<br />
●お問い合わせ:<br />
kanae [at] sys.i.kyoto-u.ac.jp<br />
までお気軽にお問合せください。<br />
<br />
●募集期間と選考方法:<br />
募集期間は ** 平成28年12月18日 ** とします。<br />
書類選考のうえ、面接により選考を行います。詳細は別途連絡したします。<br />
適任者が決まり次第、募集を終了いたします。<br />
<br />
==============<br />
<br />
当研究室には、平成28年4月現在、<br />
石井 信(数理工学)<br />
大羽成征(バイオインフォマティクス、統計科学)<br />
前田新一(情報理論、機械学習)、<br />
浦久保秀俊 (計算神経科学)<br />
近藤洋平(数理生物学)<br />
ヘンリク・スキッべ(画像情報学)<br />
中江 健(統計科学、計算神経科学)<br />
村上 陽平(システム生物学)<br />
川瀬貴士(生物画像処理)<br />
メシギ・クーロシ(画像工学、人工知能)<br />
トーステン・ブルマン(計算神経科学)<br />
の各研究者が在籍し、数理工学から脳神経科学、システム生物学、ブレインマシンインターフェースなどへの融合領域への研究展開を、沖縄科学技術大学院 (OIST)、ATR認知機構研究所、理化学研究所脳科 学総合研究センターなどの研究機関との連携の下で実施しております。<br />
<br />
研究室のホームページ<br />
http://ishiilab.jp<br />
京都大学情報学研究科システム科学専攻のホームページ<br />
http://www.sys.i.kyoto-u.ac.jp/index.html<br />
<br />
<br />
==== <span style="color: red">New!! </span> 国立研究開発法人理化学研究所、統合生命医科学研究センターオミクス研究ラボ 研究員または特別研究員 公募 ==== <br />
募集職種:研究員または特別研究員 1名<br />
<br />
職務内容:細胞生物学的手法、分子生物学的手法、免疫学的手法、シークエンス技術、光学顕微鏡、マイクロチップ技術、Bioinformaticsなどを基にして、単一細胞や少数<br />
細胞、組織を対象にした(各種免疫系細胞、腸内細菌など)新しい定量計測法の<br />
開発を行います。また、開発した方法を用いて、医科学的に重要な試料を測定<br />
し、新しい切り口でサイエンスや医科学に貢献することを目指します。<br />
<br />
勤務地:独立行政法人理化学研究所 統合生命医科学研究センター 神奈川県横浜市鶴見区末広町1-7-22<br />
<br />
着任時期:応相談<br />
<br />
研究内容についての問合せ先:<br />
国立研究開発法人理化学研究所統合生命医科学研究センター<br />
オミクス研究ラボ 城口克之<br />
E-mail: katsuyuki.shiroguchi [at]riken.jp ※[at]は@に置き換えてくだ<br />
さい。<br />
<br />
公募の詳細:<br />
http://www.riken.jp/careers/researchers/20150909/<br />
<br />
==== <span style="color: red">New!! </span>Seeking Research Scientist or Postdoctoral Researcher, Laboratory for Quantitative Omics, RIKEN Center for Integrative Medical Sciences====<br />
<br />
Available Positions: Research Scientist or Postdoctoral Researcher, one person, full-time.<br />
<br />
Job Descriptions: A successful candidate will develop new method(s) to measure parameters quantitatively from single cells, a few cells, or cells from tissues (immunological cells, microbiome, etc) based on techniques of cell<br />
biology, molecular biology, immunology, sequencing, optical microscope,<br />
microchip, and/or bioinfomatics. Using the developed method(s), she/he<br />
will measure cells which are medically significant, and intend to contribute to science and medical science from a novel point of view.<br />
<br />
Work location: RIKEN Center for Integrative Medical Sciences. 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045 Japan<br />
<br />
Start of Employment: Negotiable<br />
<br />
Inquiries for research contents<br />
Laboratory for Quantitative Omics, RIKEN Center for Integrative Medical<br />
Sciences<br />
Katsuyuki Shiroguchi<br />
Email: katsuyuki.shiroguchi[at]riken.jp<br />
<br />
Details:http://www.riken.jp/en/careers/researchers/20150909/<br />
<br />
====これまでに掲載したお知らせ====<br />
*明治大学理工学部石原研究室・生命現象の数理モデリングと理論解析を行う博士研究員の公募<br />
*ヘルシンキ大学研究員募集 (20141010)<br />
*JST・ERATO 佐藤ライブ予測制御プロジェクト研究員募集<br />
*JST CRESTプロジェクト「細胞間接着・骨格の秩序形成メカニズムの解明と上皮バリア操作技術の開発」研究員募集<br />
*京大情・論理生命学研・研究員募集<br />
*独立行政法人理化学研究所、統合生命医科学研究センター統合ゲノミクスグループ 研究員または特別研究員の公募<br />
*自然科学研究機構新分野創成センター特任研究員の公募 <br />
*沖縄科学技術大学院大学学園(OIST)バイオインフォマティシャンの求人の募集 <br />
*「生命動態の理解と制御のための基盤技術の創出」研究領域の「時間情報コードによる細胞制御システムの解明」(代表者:黒田真也(東京大学))研究員の募集 <br />
*自然科学研究機構新分野創成センター特任助教等の公募<br />
*東京大学黒田研 特任助教募集募集<br />
*Biology/Genetics/Evolution Postdoctoral Fellow Position, Fred Hutchinson Cancer Research Center (091006)</div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5060SpeakersandAbstracts2016-01-09T04:02:46Z<p>Noriko.hiroi: /* Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
===='''Anisotropy shaped by and for the dynamic distribution of heat'''====<br />
In this talk, we demonstrate how to detect the temperature increase after the mitochondrial stimulation with the sequential observation of single quantum dot, and for the first time the temperature difference within a neuronal cell by using multiple quantum dot imaging, and suggest the cause of heterogeneity of temperature by using the characteristic shape of neuronal cells based on the actual 3D observation.<br><br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br><br />
[1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br><br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). <br><br />
[3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br><br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools.<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.<br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5059SpeakersandAbstracts2016-01-09T03:46:39Z<p>Noriko.hiroi: /* Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
===='''Anisotropy shaped by and for the dynamic distribution of heat'''====<br />
In this talk, we demonstrate how to detect the temperature increase after the mitochondrial stimulation with the sequential observation of single quantum dot, and for the first time the temperature difference within a neuronal cell by using multiple quantum dot imaging, and suggest the cause of heterogeneity of temperature by using the characteristic shape of neuronal cells based on the actual 3D observation.<br><br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br><br />
[1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br><br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). <br><br />
[3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br><br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.<br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
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<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
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===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
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<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
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===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
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<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
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<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5058SpeakersandAbstracts2016-01-05T07:48:10Z<p>Noriko.hiroi: /* A physicist’s approach to the origin of life: Non-equilibrium entropic force */</p>
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<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
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==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
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Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
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===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
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===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
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Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
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<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
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<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
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==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
===='''Anisotropy shaped by and for the dynamic distribution of heat'''====<br />
In this talk, we demonstrate how to detect the temperature increase after the mitochondrial stimulation with the sequential observation of single quantum dot, and for the first time the temperature difference within a neuronal cell by using multiple quantum dot imaging, and suggest the cause of heterogeneity of temperature by using the characteristic shape of neuronal cells based on the actual 3D observation.<br><br />
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===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
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<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
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===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br><br />
[1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br><br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). <br><br />
[3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br><br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
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===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
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===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
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<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
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==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
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===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
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===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5057SpeakersandAbstracts2016-01-05T07:47:10Z<p>Noriko.hiroi: /* Noriko Hiroi ( Keio University, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
===='''Anisotropy shaped by and for the dynamic distribution of heat'''====<br />
In this talk, we demonstrate how to detect the temperature increase after the mitochondrial stimulation with the sequential observation of single quantum dot, and for the first time the temperature difference within a neuronal cell by using multiple quantum dot imaging, and suggest the cause of heterogeneity of temperature by using the characteristic shape of neuronal cells based on the actual 3D observation.<br><br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br><br />
Selected refs: [1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br><br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). <br><br />
[3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br><br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5056SpeakersandAbstracts2016-01-05T07:45:12Z<p>Noriko.hiroi: /* Noriko Hiroi ( Keio University, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
===='''Anisotropy shaped by and for the dynamic distribution of heat'''====<br />
In this talk, we demonstrate how to detect the temperature increase after the mitochondrial stimulation with the sequential observation of single quantum dot, and for the first time the temperature difference within a neuronal cell by using multiple quantum dot imaging, and suggest the cause of heterogeneity of temperature by using the characteristic shape of neuronal cells based on the actual 3D observation.<br><br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br><br />
Selected refs: [1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br><br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). <br><br />
[3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br><br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5055SpeakersandAbstracts2016-01-05T07:44:18Z<p>Noriko.hiroi: /* Noriko Hiroi ( Keio University, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br />
<br><br />
Anisotropy shaped by and for the dynamic distribution of heat<br />
In this talk, we demonstrate how to detect the temperature increase after the mitochondrial stimulation with the sequential observation of single quantum dot, and for the first time the temperature difference within a neuronal cell by using multiple quantum dot imaging, and suggest the cause of heterogeneity of temperature by using the characteristic shape of neuronal cells based on the actual 3D observation.<br><br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br><br />
Selected refs: [1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br><br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). <br><br />
[3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br><br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5054SpeakersandAbstracts2016-01-05T07:41:51Z<p>Noriko.hiroi: /* Noriko Hiroi ( Keio University, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br><br />
===='''Anisotropy shaped by and for the dynamic distribution of heat'''====<br ><br />
In this talk, we demonstrate how to detect the temperature increase after the mitochondrial stimulation with the sequential observation of single quantum dot, and for the first time the temperature difference within a neuronal cell by using multiple quantum dot imaging, and suggest the cause of heterogeneity of temperature by using the characteristic shape of neuronal cells based on the actual 3D observation.<br><br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br><br />
Selected refs: [1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br><br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). <br><br />
[3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br><br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5053SpeakersandAbstracts2016-01-05T07:40:53Z<p>Noriko.hiroi: /* Noriko Hiroi ( Keio University, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
===='''Anisotropy shaped by and for the dynamic distribution of heat'''====<br ><br />
In this talk, we demonstrate how to detect the temperature increase after the mitochondrial stimulation with the sequential observation of single quantum dot, and for the first time the temperature difference within a neuronal cell by using multiple quantum dot imaging, and suggest the cause of heterogeneity of temperature by using the characteristic shape of neuronal cells based on the actual 3D observation.<br><br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br><br />
Selected refs: [1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br><br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). <br><br />
[3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br><br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5052SpeakersandAbstracts2016-01-05T07:40:16Z<p>Noriko.hiroi: /* Noriko Hiroi ( Keio University, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
===='''Anisotropy shaped by and for the dynamic distribution of heat'''====<br ><br />
In this talk, we demonstrate how to detect the temperature increase after the mitochondrial stimulation with the sequential observation of single quantum dot, and for the first time the temperature difference within a neuronal cell by using multiple quantum dot imaging, and suggest the cause of heterogeneity of temperature by using the characteristic shape of neuronal cells based on the actual 3D observation.<br><br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br><br />
Selected refs: [1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br><br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). <br><br />
[3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br><br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5051SpeakersandAbstracts2016-01-05T07:38:27Z<p>Noriko.hiroi: /* A physicist’s approach to the origin of life: Non-equilibrium entropic force */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs:<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br><br />
Selected refs: [1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br><br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). <br><br />
[3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br><br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5050SpeakersandAbstracts2016-01-05T07:37:46Z<p>Noriko.hiroi: /* A physicist’s approach to the origin of life: Non-equilibrium entropic force */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs:<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br />
Selected refs: [1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). [3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5049SpeakersandAbstracts2016-01-05T07:37:30Z<p>Noriko.hiroi: /* Yusuke Maeda ( Kyushu University, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs:<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
===='''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''====<br />
abstract: Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br />
Selected refs: [1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). [3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=5048SpeakersandAbstracts2016-01-05T07:36:47Z<p>Noriko.hiroi: /* Yusuke Maeda ( Kyushu University, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development (this work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara). <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement (this work is done in collaboration with K. Ikawa).<br />
<br><br />
<br><br />
Selected refs: Guirao et al. ''eLife'' ('''2015'''); Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs:<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
title: '''A physicist’s approach to the origin of life: Non-equilibrium entropic force'''<br ><br />
abstract: Temperature differences at large scales, kilometers or more, are present in our planet and essential for plate tectonics and meteorological phenomena. As the earth is blessed with temperature, it has revolutionized our life: Carnot showed the operation of the heat engine in two temperature systems at the industrial revolution, which led to the second law of thermodynamics.<br />
On a smaller scale, millimeters or less, temperature differences are also present in the pores of hydrothermal vents. The motion of molecules under such temperature gradients, called thermophoresis or the Soret effect, where thermal convection is suppressed could be relevant to the inhomogeneous distribution of chemical species. Thermophoresis depletes a polymer such as polyethylene glycol (PEG) from the hot region and builds a concentration gradient. In such a solution, solutes of small concentration experience thermophoresis and the restoring force dependent on PEG gradient of large concentration. Under focused laser heating, DNA and RNA as solutes localize as a ring-like structure which diameter monotonically decreases with their size following a behavior analogous to gel electrophoresis [1]. Trapping and selection of molecules could be physically feasible in a simple way relying on temperature gradient. Thermophoresis of RNA enzyme might be relevant to primitive life: Separation of RNA from the large library of RNA world might occur at the thermal vent of the deep ocean where large temperature gradient is present [2].<br />
Moreover, because this effect relies on the entropic force in solute contrasts, trapping with little material dependence is feasible. It allows us to optically control the density of living cells and proteins [3,4].<br><br />
Selected refs: [1] YT Maeda, A Buguin, A Libchaber. Phys. Rev. Lett. 107, 038301 (2011). <br />
[2] YT Maeda, T Tlusty, A Libchaber. Proc. Natl. Acad. Sci. USA 109, 17972 (2012). [3] YT Maeda. Appl. Phys. Lett. 103, 243704 (2013).<br />
[4] T Fukuyama, et al. Langmuir 31, 12567 (2015).<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[https://engineering.purdue.edu/~dumulis/ '''David Umulis'''] ( Purdue University, USA )===<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol.'' ('''2014'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:Tsukada et al.'' J Neurosci.'' '''in press'''; Tsukada and Hashimoto ''Develop Growth Differ.'' ('''2013'''); Miyara et al. ''PLoS Genetics'' ('''2011''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br><br />
<br><br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=IIS_Sympo&diff=5047IIS Sympo2016-01-05T07:26:48Z<p>Noriko.hiroi: /* Session: Quantity - SYMMETRY I - */</p>
<hr />
<div>=='''NIG International Symposium 2016'''==<br />
This event is sponsored by National Institute of Genetics ([http://www.nig.ac.jp/nig/ NIG]) and held as the NIG International Symposium 2016.<br />
<br />
===''Tokyo Symposium at Institute of Industrial Science, the University of Tokyo''===<br />
<br />
=='''Force, Information and Dynamics: X factors shaping living systems '''==<br />
<br />
<span style="color: green">'''Exploring frontiers of quantitative biology by identifying X-factors that shape living systems'''</span><br />
<br />
'''Quantitative biology is a growing discipline goes beyond the quantification of biological phenomena and attempts to unveil fundamental and general principles governing living systems.'''<br />
<br />
'''After decades of emphasis on the study of GENES to reveal such principles, recent advances in quantitative biology have shed light on other key factors in biology, designated as X-FACTORS. X-factors include FORCE and SYMMETRY, which control the shape, size, and movement of cells and tissues, and INFORMATION, which characterizes processing and transduction of intra- and inter-cellular signaling. Enumerating such X-factors represents a milestone in quantitative biology.'''<br />
<br />
'''In the Tokyo Symposium, we shall focus on X-factors in biology. This symposium was designed to share and discuss our vision for the frontiers of quantitative biology with cutting-edge researchers from around the world. We expect active discussions on state-of-the-art techniques to measure and manipulate X-factors and on the integration of different X-factors, leading towards a deeper understanding of the nature of living systems.'''<br />
<br />
==Date: Jan 9th - 11th, 2016.==<br />
Jan. 9th 13:00 to Jan. 11th 12:00<br />
<br />
==Venue for the Symposium at Tokyo==<br />
Convention hall, An Block, Institute of Industrial Science, <br/><br />
Komaba Ⅱ Research Campus, the University of Tokyo.<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/access_e.html Access to Komaba Ⅱ Research Campus]<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/campusmap_e.html Campus map]<br />
<br />
==Registration is '''OPEN'''==<br />
'''Registration from [https://docs.google.com/forms/d/1hNiBiiLu73N0Mo9FS5O03D0LTu7VHHP-BqJtOAzoNPY/viewform?usp=send_form here].'''<br><br />
'''Please be sure that the above registration and abstract submission are both ONLY for Tokyo Symposium. '''<br />
<br/>For the registration and abstract submission to the other workshops and symposium, you may visit the other sites ([http://q-bio.jp/wiki/Events Events]).'''<br />
Seating capacity: Approximately 150, excluding invited speakers ( approx. 20 people ).<br />
<br/><br />
<br />
==Poster Abstract submission deadline: Dec. 10th, 2015<br>== <br />
'''For a poster presentation, please submit your abstract from [https://docs.google.com/forms/d/1x3dNWPk6GZDBLec_O3WFCaXsaqmis83wtzdt8f5AetM/viewform?usp=send_form here].'''<br />
<br/><br />
''After the deadline, we will still open the opportunity for poster presentation. Please feel free to submit your abstract and bring your poster. Late coming abstracts may not be included in an abstract booklet.''<br />
<br><br />
<br />
==Poster Size & Schedule== <br />
The size of poster board is w 1130[mm] × h 1630[mm].<br/><br />
Standard <span style="color: red">A0</span> (841[mm]×1189[mm]) or <span style="color: red">B0</span> (1030[mm]×1456[mm]) size poster is recommended.<br />
<br/><br />
You can put your poster from 12:00 of Jan 9th. Please remove your poster at the end of the mixer and poster session on Jan 10th. <br/><br />
<br/><br />
<span style="color: red">If you bring the same poster to the Mishima Symposium, A0 size should be fine.</span><br />
<br/><br />
<span style="color: red">Please include your photo on your poster so that participants can know who you are.</span><br />
<br/><br />
<br />
==Speakers and Abstracts==<br />
[[SpeakersandAbstracts|<span style="color: red">'''Link to a "Speakers and Abstracts" page.'''</span>]]<br />
<br />
==Talks==<br />
<span style="color: red">Presentation (35 min)+Discussion (8 min)+PC exchange (2 min)</span> <br ><br />
Note: Presentation time is different in Mishima symposium.<br />
<br />
==Scientific Program==<br />
=== Jan. 9th===<br />
-----<br />
=====Opening Remarks by Isao Karsura (NIG)=====<br />
Date and Time: Jan. 9th 13:00-13:20<br><br />
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<br />
====Session: Quantity - FORCE -====<br />
Date and Time: Jan. 9th 13:20-15:35<br><br />
Chair: '''Kaoru Sugimura and Yuta Shimamoto'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )<br><br />
"Quantifying tissue mechanics in vivo and in situ"<br />
|-<br />
!<br />
!<br />
![http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto Univ., Japan )<br><br />
"Dissecting the mechanical control of Drosophila wing shape determination"<br />
|-<br />
!<br />
!<br />
![http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )<br />
"From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction"<br />
|-<br />
|}<br />
<br />
====Poster Session I====<br />
Date and Time: Jan. 9th 15:40-18:30 including 5-min instructions for poster presentations<br><br />
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=== Jan. 10th===<br />
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====Session: Quantity - SYMMETRY I -====<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
Co-Chair: '''Noriko Hiroi and Yusuke Maeda'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )<br />
"Anisotropy shaped by and for the Dynamic Distribution of Heat"<br />
|-<br />
!<br />
!<br />
![http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )<br />
"Seeing how mammalian life starts: Quantitative imaging in live mouse embryos"<br />
|-<br />
!<br />
!<br />
![http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )<br />
"A physicist's approach to the origin of life: Non-equilibrium entropic force"<br />
|-<br />
!<br />
!<br />
![http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )<br />
"Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools"<br />
|-<br />
|}<br />
<br />
====Poster Session II====<br />
Date and Time: Jan. 10th 12:30-13:30<br><br />
<br><br><br />
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<br />
====Session: Quantity - SYMMETRY II - ====<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
'''Akatsuki Kimura and Yutaka Matsubayashi'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )<br><br />
"Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles"<br />
|-<br />
!<br />
! <br />
![http://www.nig.ac.jp/nig/research/interviews/faculty-interviews/kimura '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )<br><br />
"How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?"<br />
|-<br />
!<br />
! <br />
![http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )<br />
"Intercellular forces orchestrate contact inhibition of locomotion"<br><br />
|}<br />
<br><br />
----<br />
'''Coffee Break'''<br />
Date and Time: Jan. 10th 15:45-16:00<br><br />
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<br />
====Session: Quantity - INFORMATION -====<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
Chair: '''Yuki Tsukada and Jun-nosuke Teramae'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )<br><br />
"Revisiting cell migration mechanisms of crawling cells"<br />
|-<br />
!<br />
! <br />
![http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) <br />
"Quantification and modeling of BMP signaling during zebrafish embryo development "<br />
|-<br />
|-<br />
!<br />
!<br />
![http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )<br />
"Quantification and reconstruction of thermosensory neuronal processing in C. elegans"<br />
|-<br />
!<br />
!<br />
![http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )<br />
"Dissecting neural circuits for motion estimation in Drosophila"<br />
|}<br />
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<br />
====Mixer at the poster presentation room====<br />
Date and Time: Jan. 10th 19:00-20:30<br><br />
<br><br><br />
----<br />
----<br />
<br />
=== Jan. 11th===<br />
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====Session: Quantities and Beyond====<br />
Date and Time: Jan. 11th 9:00-11:15<br><br />
Chair: '''Naoki Irie and Tetsuya Kobayashi'''<br><br />
Speakers:<br />
{|-<br />
!<br />
! <br />
![http://www.biol.s.u-tokyo.ac.jp/users/hassei/irie/index_e.html '''Naoki Irie''']( the University of Tokyo, Japan )<br />
"Double bladed aspect of gene recruitment to morphological evolution."<br />
|-<br />
!<br />
!<br />
![http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )<br />
"Fitness and gene expression from the viewpoint of single-cell histories"<br />
|-<br />
!<br />
!<br />
! [http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )<br />
"Integrating Fitness and Information in Biological Adaptation"<br />
|}<br />
----<br />
<br />
====Open Discussion====<br />
Date and Time: Jan. 11th 11:15-12:00<br><br />
----<br />
<br />
==Links==<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br><br />
<br />
==Contacts==<br />
qbioint2016 at gmail.com<br><br />
<br><br />
Organizers: Akatsuki Kimura (NIG), Akira Funahashi (Keio Univ.), Noriko F. Hiroi (Keio Univ.), Tetsuya J. Kobayashi (Univ. Tokyo)<br><br />
<br><br />
Program committee: Kaoru Sugimura (Kyoto Univ.), Yuki Tsukada (Nagoya Univ.), Naoki Irie (Univ. Tokyo), Junnosuke Teramae (Osaka Univ), Yusuke Maeda (Kyushu Univ.)</div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=4995SpeakersandAbstracts2015-12-13T10:57:19Z<p>Noriko.hiroi: /* Noriko Hiroi ( Keio University, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development. <br />
<br><br />
This work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara. <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement.<br />
<br><br />
This work is done in collaboration with K. Ikawa.<br />
<br><br />
<br><br />
Selected refs: Guirao et al. eLife, ''in press''; Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs:<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
title: tba<br ><br />
abstract: <br><br />
Selected refs: Fukuyama et al. Langmuir (2015); Maeda et al. PNAS (2012); Maeda et al. PRL (2011)<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:<br />
<br />
===[http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) ===<br />
'''勾配情報が作り出す発生メカニズム'''<br><br />
<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol''. ('''2014'''); Peluso et al. ''Dev. Cell'' ('''2011'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=4994SpeakersandAbstracts2015-12-13T10:55:00Z<p>Noriko.hiroi: /* From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development. <br />
<br><br />
This work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara. <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement.<br />
<br><br />
This work is done in collaboration with K. Ikawa.<br />
<br><br />
<br><br />
Selected refs: Guirao et al. eLife, ''in press''; Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs: Sumiyoshi et al. Front Physiol. (2015); Hiroi et al. Front Physiol. (2014)<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
title: tba<br ><br />
abstract: <br><br />
Selected refs: Fukuyama et al. Langmuir (2015); Maeda et al. PNAS (2012); Maeda et al. PRL (2011)<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:<br />
<br />
===[http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) ===<br />
'''勾配情報が作り出す発生メカニズム'''<br><br />
<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol''. ('''2014'''); Peluso et al. ''Dev. Cell'' ('''2011'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=IIS_Sympo&diff=4993IIS Sympo2015-12-13T10:54:35Z<p>Noriko.hiroi: /* Session: Quantity - FORCE - */</p>
<hr />
<div>=='''NIG International Symposium 2016'''==<br />
This event is sponsored by National Institute of Genetics ([http://www.nig.ac.jp/nig/ NIG]) and held as the NIG International Symposium 2016.<br />
<br />
===''Tokyo Symposium at Institute of Industrial Science, the University of Tokyo''===<br />
<br />
=='''Force, Information and Dynamics: X factors shaping living systems '''==<br />
<br />
<span style="color: green">'''Exploring frontiers of quantitative biology by identifying X-factors that shape living systems'''</span><br />
<br />
'''Quantitative biology is a growing discipline goes beyond the quantification of biological phenomena and attempts to unveil fundamental and general principles governing living systems.'''<br />
<br />
'''After decades of emphasis on the study of GENES to reveal such principles, recent advances in quantitative biology have shed light on other key factors in biology, designated as X-FACTORS. X-factors include FORCE and SYMMETRY, which control the shape, size, and movement of cells and tissues, and INFORMATION, which characterizes processing and transduction of intra- and inter-cellular signaling. Enumerating such X-factors represents a milestone in quantitative biology.'''<br />
<br />
'''In the Tokyo Symposium, we shall focus on X-factors in biology. This symposium was designed to share and discuss our vision for the frontiers of quantitative biology with cutting-edge researchers from around the world. We expect active discussions on state-of-the-art techniques to measure and manipulate X-factors and on the integration of different X-factors, leading towards a deeper understanding of the nature of living systems.'''<br />
<br />
==Date: Jan 9th - 11th, 2016.==<br />
Jan. 9th 13:00 to Jan. 11th 12:00<br />
<br />
==Venue for workshops and the Symposium at Tokyo==<br />
Convention hall, An Block, Institute of Industrial Science, <br/><br />
Komaba Ⅱ Research Campus, the University of Tokyo.<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/access_e.html Access to Komaba Ⅱ Research Campus]<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/campusmap_e.html Campus map]<br />
<br />
==Registration is '''OPEN'''(Dec/10/2015)==<br />
'''Registration from [https://docs.google.com/forms/d/1hNiBiiLu73N0Mo9FS5O03D0LTu7VHHP-BqJtOAzoNPY/viewform?usp=send_form here].'''<br><br />
'''Please be sure that the above registration and abstract submission are both ONLY for Tokyo Symposium. '''<br />
<br/>For the registration and abstract submission to the other workshops and symposium, you may visit the other sites ([http://q-bio.jp/wiki/Events Events]).'''<br />
Seating capacity: Approximately 150, excluding invited speakers ( approx. 20 people ).<br />
<br/><br />
==Poster Abstract submission deadline: Dec. 10th thr. 2015<br>== <br />
'''For a poster presentation, please submit your abstract from [https://docs.google.com/forms/d/1x3dNWPk6GZDBLec_O3WFCaXsaqmis83wtzdt8f5AetM/viewform?usp=send_form here].'''<br />
<br/><br />
''After the deadline, we will still open the opportunity for poster presentation. Please feel free to submit your abstract and bring your poster''.<br><br />
''In case it will take a time to include the late posters into abstract booklet.''<br />
<br><br />
==Poster Size (Dec/10/2015)== <br />
The size of a poster panel is w 1130[mm] × h 1630[mm].<br/><br />
Standard <span style="color: red">A0</span> (841[mm]×1189[mm]) or <span style="color: red">B0</span> (1030[mm]×1456[mm]) size poster is recommended.<br />
<br/><br />
<br/><br />
<span style="color: red">When you are planning to bring the same poster to Mishima Symposium, <br />
<br><br />
A0 size poster should be fine.</span><br />
<br/><br />
<br/><br />
<br />
==Speakers and Abstracts==<br />
[[SpeakersandAbstracts|<span style="color: red">'''Link to a "Speakers and Abstracts" page.'''</span>]]<br />
<br />
==Scientific Program==<br />
=== Jan. 9th===<br />
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=====Opening Remarks=====<br />
Date and Time: Jan. 9th 13:00-13:10<br><br />
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<br />
====Session: Quantity - FORCE -====<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
Chair: '''Kaoru Sugimura'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )<br><br />
title: "Quantifying tissue mechanics in vivo and in situ"<br />
|-<br />
!<br />
!<br />
![http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto Univ., Japan )<br><br />
title: "Dissecting the mechanical control of Drosophila wing shape determination"<br />
|-<br />
!<br />
!<br />
![http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )<br />
title: "From mesoderm mechanotransductive evolutionary origins to tumourigenic mechanical induction"<br />
|-<br />
|}<br />
<br />
====Poster Session I====<br />
Date and Time: Jan. 9th 15:25-18:30 including 5-min instructions of poster presentations<br><br />
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----<br />
<br />
=== Jan. 10th===<br />
-----<br />
====Session: Quantity - SYMMETRY I -====<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
Co-Chair: '''Noriko Hiroi and Yusuke Maeda'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )<br />
title: "Anisotropy shaped by and for the Dynamic Distribution of Heat"<br />
|-<br />
!<br />
!<br />
![http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )<br />
title: "Seeing how mammalian life starts: Quantitative imaging in live mouse embryos"<br />
|-<br />
!<br />
!<br />
![http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )<br />
title: tba<br />
|-<br />
!<br />
!<br />
![http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )<br />
title: "Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools"<br />
|-<br />
|}<br />
<br />
====Poster Session II====<br />
Date and Time: Jan. 10th 12:00-13:30<br><br />
<br><br><br />
----<br />
<br />
====Session: Quantity - SYMMETRY II - ====<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
Chair: '''Akatsuki Kimura'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )<br><br />
title: "Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles"<br />
|-<br />
!<br />
! <br />
![http://www.nig.ac.jp/nig/research/interviews/faculty-interviews/kimura '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )<br><br />
title: "How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?"<br />
|-<br />
!<br />
! <br />
![http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )<br />
title: "Intercellular forces orchestrate contact inhibition of locomotion"<br><br />
|}<br />
<br><br />
----<br />
'''Coffee Break'''<br />
Date and Time: Jan. 10th 15:45-16:00<br><br />
----<br />
<br />
====Session: Quantity - INFORMATION -====<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
Chair:'''Yuki Tsukada'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )<br><br />
title: "Revisiting cell migration mechanisms of crawling cells"<br />
|-<br />
!<br />
! <br />
![http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )<br />
title: "Dissecting neural circuits for motion estimation in Drosophila"<br />
|-<br />
|-<br />
!<br />
!<br />
![http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )<br />
title: "Quantification and reconstruction of thermosensory neuronal processing in C. elegans"<br />
|-<br />
!<br />
!<br />
![http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) <br />
title: "Quantification and modeling of BMP signaling during zebrafish embryo development "<br />
|}<br />
----<br />
<br />
====Mixer at the poster presentation Hall====<br />
Date and Time: Jan. 10th 19:00-20:30<br><br />
<br><br><br />
----<br />
----<br />
<br />
=== Jan. 11th===<br />
-----<br />
====Session: Quantities and Beyond====<br />
Date and Time: Jan. 11th 9:00-11:15<br><br />
Chair: '''Naoki Irie'''<br><br />
Speakers:<br />
{|-<br />
!<br />
! <br />
![http://www.biol.s.u-tokyo.ac.jp/users/hassei/irie/index_e.html '''Naoki Irie''']( the University of Tokto, Japan )<br />
title: "Double bladed aspect of gene recruitment to morphological evolution."<br />
|-<br />
!<br />
!<br />
![http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )<br />
title: "Fitness and gene expression from the viewpoint of single-cell histories"<br />
|-<br />
!<br />
!<br />
! [http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )<br />
title: "Integrating Fitness and Information in Biological Adaptation"<br />
|}<br />
----<br />
<br />
====Open Discussion====<br />
Date and Time: Jan. 11th 11:15-12:00<br><br />
----<br />
<br />
==Links==<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br><br />
<br />
==Contacts==<br />
qbioint2016 at gmail.com<br><br />
<br><br />
Organizers: Akatsuki Kimura (NIG), Akira Funahashi (Keio Univ.), Noriko F. Hiroi (Keio Univ.), Tetsuya J. Kobayashi (Univ. Tokyo)<br><br />
<br><br />
Program committee: Kaoru Sugimura (Kyoto Univ.), Yuki Tsukada (Nagoya Univ.), Naoki Irie (Univ. Tokyo), Junnosuke Teramae (Osaka Univ), Yusuke Maeda (Kyushu Univ.)</div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=4992SpeakersandAbstracts2015-12-13T07:41:07Z<p>Noriko.hiroi: /* Nicolas D Plachta ( IMCB, Singapore ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development. <br />
<br><br />
This work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara. <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement.<br />
<br><br />
This work is done in collaboration with K. Ikawa.<br />
<br><br />
<br><br />
Selected refs: Guirao et al. eLife, ''in press''; Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs: Sumiyoshi et al. Front Physiol. (2015); Hiroi et al. Front Physiol. (2014)<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br />
===='''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''====<br />
We have established imaging tools to study how the early mammalian embryo forms. We combine photoactivation with fluorescence correlation spectroscopy techniques to show how transcription factors change their DNA binding dynamics to control cell fate, as the mouse embryo establishes its first cell lineages. We then show that as they decide their fates, cells use a new class of filopodia to pull their neighbor cells closer and achieve compaction of the embryo. Finally, we develop membrane segmentation methods to show how mechanical forces form the pluripotent inner mass of the embryo. Unlike classic models based on highly orientated cell divisions, we show that the prime mechanism forming the pluripotent inner mass is apical constriction. Using laser ablations, we discover that anisotropies in tensile forces produced by actomyosin networks control the first spatial separation of cells during development. Our findings reveal mechanisms explaining how mammalian cells choose their fate, shape and position during mammalian development. <br />
<br><br />
<br><br />
Selected refs: Samarage et al. ''Dev. Cell'' ('''2015'''); Fierro-González et al. ''Nat. Cell Biol.'' ('''2013'''); Plachta et al. ''Nat. Cell Biol''. ('''2011''')<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
title: tba<br ><br />
abstract: <br><br />
Selected refs: Fukuyama et al. Langmuir (2015); Maeda et al. PNAS (2012); Maeda et al. PRL (2011)<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:<br />
<br />
===[http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) ===<br />
'''勾配情報が作り出す発生メカニズム'''<br><br />
<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol''. ('''2014'''); Peluso et al. ''Dev. Cell'' ('''2011'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=4991SpeakersandAbstracts2015-12-13T07:38:46Z<p>Noriko.hiroi: /* Tetsuya J Kobayashi( the University of Tokyo, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development. <br />
<br><br />
This work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara. <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement.<br />
<br><br />
This work is done in collaboration with K. Ikawa.<br />
<br><br />
<br><br />
Selected refs: Guirao et al. eLife, ''in press''; Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs: Sumiyoshi et al. Front Physiol. (2015); Hiroi et al. Front Physiol. (2014)<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br><br />
<br />
'''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''<br ><br />
abstract: <br><br />
Selected refs: Samarage et al. Dev. Cell (2015); Fierro-González et al. Nat. Cell Biol. (2013); Plachta et al. Nat. Cell Biol. (2011)<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
title: tba<br ><br />
abstract: <br><br />
Selected refs: Fukuyama et al. Langmuir (2015); Maeda et al. PNAS (2012); Maeda et al. PRL (2011)<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:<br />
<br />
===[http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) ===<br />
'''勾配情報が作り出す発生メカニズム'''<br><br />
<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol''. ('''2014'''); Peluso et al. ''Dev. Cell'' ('''2011'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br />
===='''Integrating Fitness and Information in Biological Adaptation'''====<br />
A cell can adapt to fluctuating environment by actively controlling its state based on the information on the environment obtained by sensing the environment.<br><br />
Information and associated information measures are fundamental notion and quantities to characterize such active adaptation of cells and its efficiency.<br />
Even without sensing, however, the cells as a population can also adapt to the changing environment passively by natural selection if the population has sufficient diversity in genetic and phenotypic states. <br />
Such passive adaptation by selection is characterized by fitness that quantifies the success of the population.<br />
In real biological systems, however, both mechanisms of the adaptation are mixed, and therefore linking information and fitness, two apparently different quantities, is crucial to understand biological adaptation.<br />
<br><br />
In this work, by introducing a retrospective view of single-cell histories, we show that information and fitness can be unified theoretically in the problem of biological adaptations as is the case with the unification of entropy and information in information thermodynamics (Maxwell’s demon problem). <br />
The integrated theory shows that not only average but also the fluctuation of fitness and information are mutually constrained via fluctuation relations.<br />
We also would like to discuss how we can unify various quantities (X-factors) that associates with different biological phenomena.<br />
<br><br />
Selected refs: Kobayashi and Sughiyama. '''PRL''' (''2015''); Kobayashi. '''PRL''' (''2011''); Kobayashi. '''PRL''' (''2010'')<br />
<br><br />
<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=IIS_Sympo&diff=4990IIS Sympo2015-12-13T07:36:51Z<p>Noriko.hiroi: /* Session: Quantities and Beyond */</p>
<hr />
<div>=='''NIG International Symposium 2016'''==<br />
This event is sponsored by National Institute of Genetics ([http://www.nig.ac.jp/nig/ NIG]) and held as the NIG International Symposium 2016.<br />
<br />
===''Tokyo Symposium at Institute of Industrial Science, the University of Tokyo''===<br />
<br />
=='''Force, Information and Dynamics: X factors shaping living systems '''==<br />
<br />
<span style="color: green">'''Exploring frontiers of quantitative biology by identifying X-factors that shape living systems'''</span><br />
<br />
'''Quantitative biology is a growing discipline goes beyond the quantification of biological phenomena and attempts to unveil fundamental and general principles governing living systems.'''<br />
<br />
'''After decades of emphasis on the study of GENES to reveal such principles, recent advances in quantitative biology have shed light on other key factors in biology, designated as X-FACTORS. X-factors include FORCE and SYMMETRY, which control the shape, size, and movement of cells and tissues, and INFORMATION, which characterizes processing and transduction of intra- and inter-cellular signaling. Enumerating such X-factors represents a milestone in quantitative biology.'''<br />
<br />
'''In the Tokyo Symposium, we shall focus on X-factors in biology. This symposium was designed to share and discuss our vision for the frontiers of quantitative biology with cutting-edge researchers from around the world. We expect active discussions on state-of-the-art techniques to measure and manipulate X-factors and on the integration of different X-factors, leading towards a deeper understanding of the nature of living systems.'''<br />
<br />
==Date: Jan 9th - 11th, 2016.==<br />
Jan. 9th 13:00 to Jan. 11th 12:00<br />
<br />
==Venue for workshops and the Symposium at Tokyo==<br />
Convention hall, An Block, Institute of Industrial Science, <br/><br />
Komaba Ⅱ Research Campus, the University of Tokyo.<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/access_e.html Access to Komaba Ⅱ Research Campus]<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/campusmap_e.html Campus map]<br />
<br />
==Registration is '''OPEN'''(Dec/10/2015)==<br />
'''Registration from [https://docs.google.com/forms/d/1hNiBiiLu73N0Mo9FS5O03D0LTu7VHHP-BqJtOAzoNPY/viewform?usp=send_form here].'''<br><br />
'''Please be sure that the above registration and abstract submission are both ONLY for Tokyo Symposium. '''<br />
<br/>For the registration and abstract submission to the other workshops and symposium, you may visit the other sites ([http://q-bio.jp/wiki/Events Events]).'''<br />
Seating capacity: Approximately 150, excluding invited speakers ( approx. 20 people ).<br />
<br/><br />
==Poster Abstract submission deadline: Dec. 10th thr. 2015<br>== <br />
'''For a poster presentation, please submit your abstract from [https://docs.google.com/forms/d/1x3dNWPk6GZDBLec_O3WFCaXsaqmis83wtzdt8f5AetM/viewform?usp=send_form here].'''<br />
<br/><br />
''After the deadline, we will still open the opportunity for poster presentation. Please feel free to submit your abstract and bring your poster''.<br><br />
''In case it will take a time to include the late posters into abstract booklet.''<br />
<br><br />
==Poster Size (Dec/10/2015)== <br />
The size of a poster panel is w 1130[mm] × h 1630[mm].<br/><br />
Standard <span style="color: red">A0</span> (841[mm]×1189[mm]) or <span style="color: red">B0</span> (1030[mm]×1456[mm]) size poster is recommended.<br />
<br/><br />
<br/><br />
<span style="color: red">When you are planning to bring the same poster to Mishima Symposium, <br />
<br><br />
A0 size poster should be fine.</span><br />
<br/><br />
<br/><br />
<br />
==Speakers and Abstracts==<br />
[[SpeakersandAbstracts|<span style="color: red">'''Link to a "Speakers and Abstracts" page.'''</span>]]<br />
<br />
==Scientific Program==<br />
=== Jan. 9th===<br />
-----<br />
=====Opening Remarks=====<br />
Date and Time: Jan. 9th 13:00-13:10<br><br />
-----<br />
<br />
====Session: Quantity - FORCE -====<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
Chair: '''Kaoru Sugimura'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )<br><br />
title: "Quantifying tissue mechanics in vivo and in situ"<br />
|-<br />
!<br />
!<br />
![http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto Univ., Japan )<br><br />
title: "Dissecting the mechanical control of Drosophila wing shape determination"<br />
|-<br />
!<br />
!<br />
![http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )<br />
title: "From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction"<br />
|-<br />
|}<br />
<br />
====Poster Session I====<br />
Date and Time: Jan. 9th 15:25-18:30 including 5-min instructions of poster presentations<br><br />
<br />
----<br />
----<br />
<br />
=== Jan. 10th===<br />
-----<br />
====Session: Quantity - SYMMETRY I -====<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
Co-Chair: '''Noriko Hiroi and Yusuke Maeda'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )<br />
title: "Anisotropy shaped by and for the Dynamic Distribution of Heat"<br />
|-<br />
!<br />
!<br />
![http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )<br />
title: "Seeing how mammalian life starts: Quantitative imaging in live mouse embryos"<br />
|-<br />
!<br />
!<br />
![http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )<br />
title: tba<br />
|-<br />
!<br />
!<br />
![http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )<br />
title: "Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools"<br />
|-<br />
|}<br />
<br />
====Poster Session II====<br />
Date and Time: Jan. 10th 12:00-13:30<br><br />
<br><br><br />
----<br />
<br />
====Session: Quantity - SYMMETRY II - ====<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
Chair: '''Akatsuki Kimura'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )<br><br />
title: "Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles"<br />
|-<br />
!<br />
! <br />
![http://www.nig.ac.jp/nig/research/interviews/faculty-interviews/kimura '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )<br><br />
title: "How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?"<br />
|-<br />
!<br />
! <br />
![http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )<br />
title: "Intercellular forces orchestrate contact inhibition of locomotion"<br><br />
|}<br />
<br><br />
----<br />
'''Coffee Break'''<br />
Date and Time: Jan. 10th 15:45-16:00<br><br />
----<br />
<br />
====Session: Quantity - INFORMATION -====<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
Chair:'''Yuki Tsukada'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )<br><br />
title: "Revisiting cell migration mechanisms of crawling cells"<br />
|-<br />
!<br />
! <br />
![http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )<br />
title: "Dissecting neural circuits for motion estimation in Drosophila"<br />
|-<br />
|-<br />
!<br />
!<br />
![http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )<br />
title: "Quantification and reconstruction of thermosensory neuronal processing in C. elegans"<br />
|-<br />
!<br />
!<br />
![http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) <br />
title: "Quantification and modeling of BMP signaling during zebrafish embryo development "<br />
|}<br />
----<br />
<br />
====Mixer at the poster presentation Hall====<br />
Date and Time: Jan. 10th 19:00-20:30<br><br />
<br><br><br />
----<br />
----<br />
<br />
=== Jan. 11th===<br />
-----<br />
====Session: Quantities and Beyond====<br />
Date and Time: Jan. 11th 9:00-11:15<br><br />
Chair: '''Naoki Irie'''<br><br />
Speakers:<br />
{|-<br />
!<br />
! <br />
![http://www.biol.s.u-tokyo.ac.jp/users/hassei/irie/index_e.html '''Naoki Irie''']( the University of Tokto, Japan )<br />
title: "Double bladed aspect of gene recruitment to morphological evolution."<br />
|-<br />
!<br />
!<br />
![http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )<br />
title: "Fitness and gene expression from the viewpoint of single-cell histories"<br />
|-<br />
!<br />
!<br />
! [http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )<br />
title: "Integrating Fitness and Information in Biological Adaptation"<br />
|}<br />
----<br />
<br />
====Open Discussion====<br />
Date and Time: Jan. 11th 11:15-12:00<br><br />
----<br />
<br />
==Links==<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br><br />
<br />
==Contacts==<br />
qbioint2016 at gmail.com<br><br />
<br><br />
Organizers: Akatsuki Kimura (NIG), Akira Funahashi (Keio Univ.), Noriko F. Hiroi (Keio Univ.), Tetsuya J. Kobayashi (Univ. Tokyo)<br><br />
<br><br />
Program committee: Kaoru Sugimura (Kyoto Univ.), Yuki Tsukada (Nagoya Univ.), Naoki Irie (Univ. Tokyo), Junnosuke Teramae (Osaka Univ), Yusuke Maeda (Kyushu Univ.)</div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=4989SpeakersandAbstracts2015-12-13T07:36:01Z<p>Noriko.hiroi: /* Yuki Tsukada ( Nagoya University, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development. <br />
<br><br />
This work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara. <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement.<br />
<br><br />
This work is done in collaboration with K. Ikawa.<br />
<br><br />
<br><br />
Selected refs: Guirao et al. eLife, ''in press''; Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs: Sumiyoshi et al. Front Physiol. (2015); Hiroi et al. Front Physiol. (2014)<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br><br />
<br />
'''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''<br ><br />
abstract: <br><br />
Selected refs: Samarage et al. Dev. Cell (2015); Fierro-González et al. Nat. Cell Biol. (2013); Plachta et al. Nat. Cell Biol. (2011)<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
title: tba<br ><br />
abstract: <br><br />
Selected refs: Fukuyama et al. Langmuir (2015); Maeda et al. PNAS (2012); Maeda et al. PRL (2011)<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br />
===='''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''====<br />
How do neural circuits encode environmental information? During navigation, animals process temporal sequences of sensory inputs to evaluate their surrounding environment. An encoding mechanism of the temporal sensory signals to grasp environmental landscape is a fundamental operation for navigating animals. To elucidate how a sensory system transforms the environmental information to temporal neural activity, we focused on a thermosensory neuron AFD in a nematode Caenorhabditis elegans, which plays a major role in a temperature dependent navigational behavior called thermotaxis. Thermotaxis is observed when we cultivate worms in a constant temperature with plenty of food, and then locate them on a thermal gradient without food: the worms migrate to the conditioned temperature region. A pair of AFD thermosensory neurons is essential for the animals to migrate toward the memorized temperature region on a thermal gradient, and is known to show calcium increase in response to temperature stimulus of the memorized temperature. However, encoding mechanisms of the temporal AFD activity during navigation remains to be elucidated. We developed simultaneous calcium imaging and tracking system for a freely-moving animal on a thermal gradient, and characterized the response property of AFD neuron to the thermal stimulus during thermotaxis. Our data of AFD neuronal activities in freely moving animals show that the AFD responds to shallow temperature increases as intermittent calcium pulses and detects temperature differential with critical time window of 20 seconds, which is similar to the time scale of behavioral elements of C. elegans such as turning. We constructed a model for AFD activity based on the identified response kernel, and reconstructed the AFD activity from a time course of observed thermal stimulus. Conversely, deconvolution of the identified response kernel and AFD activity accurately reconstructs the shallow thermal gradient with migration trajectory, indicating that AFD activity and the migration trajectory are sufficient as the encoded signals for thermal environment. Our study demonstrates bidirectional transformation between environmental thermal information and encoded neural activity. <br />
<br><br />
<br><br />
Selected refs:<br />
<br />
===[http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) ===<br />
'''勾配情報が作り出す発生メカニズム'''<br><br />
<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol''. ('''2014'''); Peluso et al. ''Dev. Cell'' ('''2011'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br><br />
<br />
'''Linking quantities from information to fitness'''<br><br />
abstract: <br><br />
Selected refs: Kobayashi and Sughiyama. PRL (2015); Kobayashi. PRL (2011); Kobayashi. PRL (2010)<br />
<br><br />
<br><br />
<br><br />
<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=IIS_Sympo&diff=4988IIS Sympo2015-12-13T07:35:14Z<p>Noriko.hiroi: /* Session: Quantity - INFORMATION - */</p>
<hr />
<div>=='''NIG International Symposium 2016'''==<br />
This event is sponsored by National Institute of Genetics ([http://www.nig.ac.jp/nig/ NIG]) and held as the NIG International Symposium 2016.<br />
<br />
===''Tokyo Symposium at Institute of Industrial Science, the University of Tokyo''===<br />
<br />
=='''Force, Information and Dynamics: X factors shaping living systems '''==<br />
<br />
<span style="color: green">'''Exploring frontiers of quantitative biology by identifying X-factors that shape living systems'''</span><br />
<br />
'''Quantitative biology is a growing discipline goes beyond the quantification of biological phenomena and attempts to unveil fundamental and general principles governing living systems.'''<br />
<br />
'''After decades of emphasis on the study of GENES to reveal such principles, recent advances in quantitative biology have shed light on other key factors in biology, designated as X-FACTORS. X-factors include FORCE and SYMMETRY, which control the shape, size, and movement of cells and tissues, and INFORMATION, which characterizes processing and transduction of intra- and inter-cellular signaling. Enumerating such X-factors represents a milestone in quantitative biology.'''<br />
<br />
'''In the Tokyo Symposium, we shall focus on X-factors in biology. This symposium was designed to share and discuss our vision for the frontiers of quantitative biology with cutting-edge researchers from around the world. We expect active discussions on state-of-the-art techniques to measure and manipulate X-factors and on the integration of different X-factors, leading towards a deeper understanding of the nature of living systems.'''<br />
<br />
==Date: Jan 9th - 11th, 2016.==<br />
Jan. 9th 13:00 to Jan. 11th 12:00<br />
<br />
==Venue for workshops and the Symposium at Tokyo==<br />
Convention hall, An Block, Institute of Industrial Science, <br/><br />
Komaba Ⅱ Research Campus, the University of Tokyo.<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/access_e.html Access to Komaba Ⅱ Research Campus]<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/campusmap_e.html Campus map]<br />
<br />
==Registration is '''OPEN'''(Dec/10/2015)==<br />
'''Registration from [https://docs.google.com/forms/d/1hNiBiiLu73N0Mo9FS5O03D0LTu7VHHP-BqJtOAzoNPY/viewform?usp=send_form here].'''<br><br />
'''Please be sure that the above registration and abstract submission are both ONLY for Tokyo Symposium. '''<br />
<br/>For the registration and abstract submission to the other workshops and symposium, you may visit the other sites ([http://q-bio.jp/wiki/Events Events]).'''<br />
Seating capacity: Approximately 150, excluding invited speakers ( approx. 20 people ).<br />
<br/><br />
==Poster Abstract submission deadline: Dec. 10th thr. 2015<br>== <br />
'''For a poster presentation, please submit your abstract from [https://docs.google.com/forms/d/1x3dNWPk6GZDBLec_O3WFCaXsaqmis83wtzdt8f5AetM/viewform?usp=send_form here].'''<br />
<br/><br />
''After the deadline, we will still open the opportunity for poster presentation. Please feel free to submit your abstract and bring your poster''.<br><br />
''In case it will take a time to include the late posters into abstract booklet.''<br />
<br><br />
==Poster Size (Dec/10/2015)== <br />
The size of a poster panel is w 1130[mm] × h 1630[mm].<br/><br />
Standard <span style="color: red">A0</span> (841[mm]×1189[mm]) or <span style="color: red">B0</span> (1030[mm]×1456[mm]) size poster is recommended.<br />
<br/><br />
<br/><br />
<span style="color: red">When you are planning to bring the same poster to Mishima Symposium, <br />
<br><br />
A0 size poster should be fine.</span><br />
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<br/><br />
<br />
==Speakers and Abstracts==<br />
[[SpeakersandAbstracts|<span style="color: red">'''Link to a "Speakers and Abstracts" page.'''</span>]]<br />
<br />
==Scientific Program==<br />
=== Jan. 9th===<br />
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=====Opening Remarks=====<br />
Date and Time: Jan. 9th 13:00-13:10<br><br />
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<br />
====Session: Quantity - FORCE -====<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
Chair: '''Kaoru Sugimura'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )<br><br />
title: "Quantifying tissue mechanics in vivo and in situ"<br />
|-<br />
!<br />
!<br />
![http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto Univ., Japan )<br><br />
title: "Dissecting the mechanical control of Drosophila wing shape determination"<br />
|-<br />
!<br />
!<br />
![http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )<br />
title: "From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction"<br />
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|}<br />
<br />
====Poster Session I====<br />
Date and Time: Jan. 9th 15:25-18:30 including 5-min instructions of poster presentations<br><br />
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=== Jan. 10th===<br />
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====Session: Quantity - SYMMETRY I -====<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
Co-Chair: '''Noriko Hiroi and Yusuke Maeda'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )<br />
title: "Anisotropy shaped by and for the Dynamic Distribution of Heat"<br />
|-<br />
!<br />
!<br />
![http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )<br />
title: "Seeing how mammalian life starts: Quantitative imaging in live mouse embryos"<br />
|-<br />
!<br />
!<br />
![http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )<br />
title: tba<br />
|-<br />
!<br />
!<br />
![http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )<br />
title: "Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools"<br />
|-<br />
|}<br />
<br />
====Poster Session II====<br />
Date and Time: Jan. 10th 12:00-13:30<br><br />
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<br />
====Session: Quantity - SYMMETRY II - ====<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
Chair: '''Akatsuki Kimura'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )<br><br />
title: "Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles"<br />
|-<br />
!<br />
! <br />
![http://www.nig.ac.jp/nig/research/interviews/faculty-interviews/kimura '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )<br><br />
title: "How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?"<br />
|-<br />
!<br />
! <br />
![http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )<br />
title: "Intercellular forces orchestrate contact inhibition of locomotion"<br><br />
|}<br />
<br><br />
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'''Coffee Break'''<br />
Date and Time: Jan. 10th 15:45-16:00<br><br />
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<br />
====Session: Quantity - INFORMATION -====<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
Chair:'''Yuki Tsukada'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )<br><br />
title: "Revisiting cell migration mechanisms of crawling cells"<br />
|-<br />
!<br />
! <br />
![http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )<br />
title: "Dissecting neural circuits for motion estimation in Drosophila"<br />
|-<br />
|-<br />
!<br />
!<br />
![http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )<br />
title: "Quantification and reconstruction of thermosensory neuronal processing in C. elegans"<br />
|-<br />
!<br />
!<br />
![http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) <br />
title: "Quantification and modeling of BMP signaling during zebrafish embryo development "<br />
|}<br />
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<br />
====Mixer at the poster presentation Hall====<br />
Date and Time: Jan. 10th 19:00-20:30<br><br />
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<br />
=== Jan. 11th===<br />
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====Session: Quantities and Beyond====<br />
Date and Time: Jan. 11th 9:00-11:15<br><br />
Chair: '''Naoki Irie'''<br><br />
Speakers:<br />
{|-<br />
!<br />
! <br />
![http://www.biol.s.u-tokyo.ac.jp/users/hassei/irie/index_e.html '''Naoki Irie''']( the University of Tokto, Japan )<br />
title: "Double bladed aspect of gene recruitment to morphological evolution."<br />
|-<br />
!<br />
!<br />
![http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )<br />
title: "Fitness and gene expression from the viewpoint of single-cell histories"<br />
|-<br />
!<br />
!<br />
! [http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )<br />
title: "Linking Quantities from Information to Fitness"<br />
|}<br />
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<br />
====Open Discussion====<br />
Date and Time: Jan. 11th 11:15-12:00<br><br />
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<br />
==Links==<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br><br />
<br />
==Contacts==<br />
qbioint2016 at gmail.com<br><br />
<br><br />
Organizers: Akatsuki Kimura (NIG), Akira Funahashi (Keio Univ.), Noriko F. Hiroi (Keio Univ.), Tetsuya J. Kobayashi (Univ. Tokyo)<br><br />
<br><br />
Program committee: Kaoru Sugimura (Kyoto Univ.), Yuki Tsukada (Nagoya Univ.), Naoki Irie (Univ. Tokyo), Junnosuke Teramae (Osaka Univ), Yusuke Maeda (Kyushu Univ.)</div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=4987SpeakersandAbstracts2015-12-13T07:34:40Z<p>Noriko.hiroi: /* Naoki Irie( the University of Tokto, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development. <br />
<br><br />
This work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara. <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement.<br />
<br><br />
This work is done in collaboration with K. Ikawa.<br />
<br><br />
<br><br />
Selected refs: Guirao et al. eLife, ''in press''; Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs: Sumiyoshi et al. Front Physiol. (2015); Hiroi et al. Front Physiol. (2014)<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br><br />
<br />
'''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''<br ><br />
abstract: <br><br />
Selected refs: Samarage et al. Dev. Cell (2015); Fierro-González et al. Nat. Cell Biol. (2013); Plachta et al. Nat. Cell Biol. (2011)<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
title: tba<br ><br />
abstract: <br><br />
Selected refs: Fukuyama et al. Langmuir (2015); Maeda et al. PNAS (2012); Maeda et al. PRL (2011)<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br><br />
<br />
'''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''<br><br />
abstract: <br><br />
Selected refs:<br />
<br />
===[http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) ===<br />
'''勾配情報が作り出す発生メカニズム'''<br><br />
<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol''. ('''2014'''); Peluso et al. ''Dev. Cell'' ('''2011'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br />
===='''Double bladed aspect of gene recruitment to morphological evolution.'''====<br />
What makes animal body plans to be conserved over 550 million years of evolution? Recently supported, the developmental hourglass model provided attractive explanation for this; Developmental system in mid-embryonic organogenesis stage has less flexibility (fragile, constrained), and thus become evolutionarily conserved. However, no quantitative, empirical evidence has been provided for this assumption. <br />
To test the above hypothesis, we have investigated the fragility of mid-embryonic developmental systems by adding fluctuations and mutations to vertebrate embryos. Our results indicated that mid-embryonic stages are not necessarily fragile, suggesting lethality of certain embryonic stage is not sufficient to explain the hourglass-like divergence. To further investigate molecular characteristics of developmental system at mid-embyonic stages, we have collected and analyzed transcriptome data obtained from early to late embryos of 8 chordate species, and found that developmental program at vertebrate mid-embryonic stages have common characteristics such as regulatory quiescence and higher pleiotropy. Based on these findings, here we propose potential mechanism that made chordate body plan conserved. Ideas for potential collaborations are welcomed, and I also appreciate critical feedback on our proposals. <br />
<br><br />
<br><br />
Selected refs: Wang et al. ''Nat. Genetics'' ('''2013'''); Irie and Kuratani. ''Nat. Commun''. ('''2011''')<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br><br />
<br />
'''Linking quantities from information to fitness'''<br><br />
abstract: <br><br />
Selected refs: Kobayashi and Sughiyama. PRL (2015); Kobayashi. PRL (2011); Kobayashi. PRL (2010)<br />
<br><br />
<br><br />
<br><br />
<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=IIS_Sympo&diff=4986IIS Sympo2015-12-13T07:33:14Z<p>Noriko.hiroi: /* Session: Quantities and Beyond */</p>
<hr />
<div>=='''NIG International Symposium 2016'''==<br />
This event is sponsored by National Institute of Genetics ([http://www.nig.ac.jp/nig/ NIG]) and held as the NIG International Symposium 2016.<br />
<br />
===''Tokyo Symposium at Institute of Industrial Science, the University of Tokyo''===<br />
<br />
=='''Force, Information and Dynamics: X factors shaping living systems '''==<br />
<br />
<span style="color: green">'''Exploring frontiers of quantitative biology by identifying X-factors that shape living systems'''</span><br />
<br />
'''Quantitative biology is a growing discipline goes beyond the quantification of biological phenomena and attempts to unveil fundamental and general principles governing living systems.'''<br />
<br />
'''After decades of emphasis on the study of GENES to reveal such principles, recent advances in quantitative biology have shed light on other key factors in biology, designated as X-FACTORS. X-factors include FORCE and SYMMETRY, which control the shape, size, and movement of cells and tissues, and INFORMATION, which characterizes processing and transduction of intra- and inter-cellular signaling. Enumerating such X-factors represents a milestone in quantitative biology.'''<br />
<br />
'''In the Tokyo Symposium, we shall focus on X-factors in biology. This symposium was designed to share and discuss our vision for the frontiers of quantitative biology with cutting-edge researchers from around the world. We expect active discussions on state-of-the-art techniques to measure and manipulate X-factors and on the integration of different X-factors, leading towards a deeper understanding of the nature of living systems.'''<br />
<br />
==Date: Jan 9th - 11th, 2016.==<br />
Jan. 9th 13:00 to Jan. 11th 12:00<br />
<br />
==Venue for workshops and the Symposium at Tokyo==<br />
Convention hall, An Block, Institute of Industrial Science, <br/><br />
Komaba Ⅱ Research Campus, the University of Tokyo.<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/access_e.html Access to Komaba Ⅱ Research Campus]<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/campusmap_e.html Campus map]<br />
<br />
==Registration is '''OPEN'''(Dec/10/2015)==<br />
'''Registration from [https://docs.google.com/forms/d/1hNiBiiLu73N0Mo9FS5O03D0LTu7VHHP-BqJtOAzoNPY/viewform?usp=send_form here].'''<br><br />
'''Please be sure that the above registration and abstract submission are both ONLY for Tokyo Symposium. '''<br />
<br/>For the registration and abstract submission to the other workshops and symposium, you may visit the other sites ([http://q-bio.jp/wiki/Events Events]).'''<br />
Seating capacity: Approximately 150, excluding invited speakers ( approx. 20 people ).<br />
<br/><br />
==Poster Abstract submission deadline: Dec. 10th thr. 2015<br>== <br />
'''For a poster presentation, please submit your abstract from [https://docs.google.com/forms/d/1x3dNWPk6GZDBLec_O3WFCaXsaqmis83wtzdt8f5AetM/viewform?usp=send_form here].'''<br />
<br/><br />
''After the deadline, we will still open the opportunity for poster presentation. Please feel free to submit your abstract and bring your poster''.<br><br />
''In case it will take a time to include the late posters into abstract booklet.''<br />
<br><br />
==Poster Size (Dec/10/2015)== <br />
The size of a poster panel is w 1130[mm] × h 1630[mm].<br/><br />
Standard <span style="color: red">A0</span> (841[mm]×1189[mm]) or <span style="color: red">B0</span> (1030[mm]×1456[mm]) size poster is recommended.<br />
<br/><br />
<br/><br />
<span style="color: red">When you are planning to bring the same poster to Mishima Symposium, <br />
<br><br />
A0 size poster should be fine.</span><br />
<br/><br />
<br/><br />
<br />
==Speakers and Abstracts==<br />
[[SpeakersandAbstracts|<span style="color: red">'''Link to a "Speakers and Abstracts" page.'''</span>]]<br />
<br />
==Scientific Program==<br />
=== Jan. 9th===<br />
-----<br />
=====Opening Remarks=====<br />
Date and Time: Jan. 9th 13:00-13:10<br><br />
-----<br />
<br />
====Session: Quantity - FORCE -====<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
Chair: '''Kaoru Sugimura'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )<br><br />
title: "Quantifying tissue mechanics in vivo and in situ"<br />
|-<br />
!<br />
!<br />
![http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto Univ., Japan )<br><br />
title: "Dissecting the mechanical control of Drosophila wing shape determination"<br />
|-<br />
!<br />
!<br />
![http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )<br />
title: "From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction"<br />
|-<br />
|}<br />
<br />
====Poster Session I====<br />
Date and Time: Jan. 9th 15:25-18:30 including 5-min instructions of poster presentations<br><br />
<br />
----<br />
----<br />
<br />
=== Jan. 10th===<br />
-----<br />
====Session: Quantity - SYMMETRY I -====<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
Co-Chair: '''Noriko Hiroi and Yusuke Maeda'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )<br />
title: "Anisotropy shaped by and for the Dynamic Distribution of Heat"<br />
|-<br />
!<br />
!<br />
![http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )<br />
title: "Seeing how mammalian life starts: Quantitative imaging in live mouse embryos"<br />
|-<br />
!<br />
!<br />
![http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )<br />
title: tba<br />
|-<br />
!<br />
!<br />
![http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )<br />
title: "Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools"<br />
|-<br />
|}<br />
<br />
====Poster Session II====<br />
Date and Time: Jan. 10th 12:00-13:30<br><br />
<br><br><br />
----<br />
<br />
====Session: Quantity - SYMMETRY II - ====<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
Chair: '''Akatsuki Kimura'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )<br><br />
title: "Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles"<br />
|-<br />
!<br />
! <br />
![http://www.nig.ac.jp/nig/research/interviews/faculty-interviews/kimura '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )<br><br />
title: "How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?"<br />
|-<br />
!<br />
! <br />
![http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )<br />
title: "Intercellular forces orchestrate contact inhibition of locomotion"<br><br />
|}<br />
<br><br />
----<br />
'''Coffee Break'''<br />
Date and Time: Jan. 10th 15:45-16:00<br><br />
----<br />
<br />
====Session: Quantity - INFORMATION -====<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
Chair:'''Yuki Tsukada'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )<br><br />
title: "Revisiting cell migration mechanisms of crawling cells"<br />
|-<br />
!<br />
! <br />
![http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )<br />
title: "Dissecting neural circuits for motion estimation in Drosophila"<br />
|-<br />
|-<br />
!<br />
!<br />
![http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )<br />
title: "Quantification and reconstruction of thermosensory neuronal processing<br />
in C. elegans"<br />
|-<br />
!<br />
!<br />
![http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) <br />
title: "Quantification and modeling of BMP signaling during zebrafish embryo development "<br />
|}<br />
----<br />
<br />
====Mixer at the poster presentation Hall====<br />
Date and Time: Jan. 10th 19:00-20:30<br><br />
<br><br><br />
----<br />
----<br />
<br />
=== Jan. 11th===<br />
-----<br />
====Session: Quantities and Beyond====<br />
Date and Time: Jan. 11th 9:00-11:15<br><br />
Chair: '''Naoki Irie'''<br><br />
Speakers:<br />
{|-<br />
!<br />
! <br />
![http://www.biol.s.u-tokyo.ac.jp/users/hassei/irie/index_e.html '''Naoki Irie''']( the University of Tokto, Japan )<br />
title: "Double bladed aspect of gene recruitment to morphological evolution."<br />
|-<br />
!<br />
!<br />
![http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )<br />
title: "Fitness and gene expression from the viewpoint of single-cell histories"<br />
|-<br />
!<br />
!<br />
! [http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )<br />
title: "Linking Quantities from Information to Fitness"<br />
|}<br />
----<br />
<br />
====Open Discussion====<br />
Date and Time: Jan. 11th 11:15-12:00<br><br />
----<br />
<br />
==Links==<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br><br />
<br />
==Contacts==<br />
qbioint2016 at gmail.com<br><br />
<br><br />
Organizers: Akatsuki Kimura (NIG), Akira Funahashi (Keio Univ.), Noriko F. Hiroi (Keio Univ.), Tetsuya J. Kobayashi (Univ. Tokyo)<br><br />
<br><br />
Program committee: Kaoru Sugimura (Kyoto Univ.), Yuki Tsukada (Nagoya Univ.), Naoki Irie (Univ. Tokyo), Junnosuke Teramae (Osaka Univ), Yusuke Maeda (Kyushu Univ.)</div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=4985SpeakersandAbstracts2015-12-13T07:32:03Z<p>Noriko.hiroi: /* Damon Clark ( Yale University, USA ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development. <br />
<br><br />
This work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara. <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement.<br />
<br><br />
This work is done in collaboration with K. Ikawa.<br />
<br><br />
<br><br />
Selected refs: Guirao et al. eLife, ''in press''; Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs: Sumiyoshi et al. Front Physiol. (2015); Hiroi et al. Front Physiol. (2014)<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br><br />
<br />
'''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''<br ><br />
abstract: <br><br />
Selected refs: Samarage et al. Dev. Cell (2015); Fierro-González et al. Nat. Cell Biol. (2013); Plachta et al. Nat. Cell Biol. (2011)<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
title: tba<br ><br />
abstract: <br><br />
Selected refs: Fukuyama et al. Langmuir (2015); Maeda et al. PNAS (2012); Maeda et al. PRL (2011)<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br />
===='''Dissecting neural circuits for motion estimation in Drosophila'''====<br />
Many sighted animals use visual signals to estimate motion. In order to estimate visual motion, animals must use nonlinear processing to integrate visual information over time and space, making visual motion estimation a paradigm of neural computation. In insects, including the fruit fly Drosophila, the neural and behavioral responses to visual motion have historically been well predicted by a model known as the Hassenstein-Reichardt correlator (HRC). To detect motion, this model correlates two inputs by delaying one before multiplying them together. However, the operations that implement the neuronal motion detector have yet to be quantified. We have used calcium imaging to measure the response properties of single local motion detectors in Drosophila’s visual circuits. We have used these measurements to characterize the timescales and lengthscales on which visual correlations are computed, as well as the types of correlations computed by different cell types. We find that the fly’s motion estimators are most sensitive to correlations on the ~20 ms timescale. Strikingly, these cell types respond to specific correlations in a manner not predicted by the HRC. Our results show that fly direction-selective cells are responsive to a spatially-structured and complementary set of fast timescale correlations.<br />
<br><br />
<br><br />
Selected refs: Fitzgerald and Clark. ''eLife'' ('''2015'''); Clark et al. ''Nat. Neurosci''. ('''2014'''); Clark et al. ''Neuron'' ('''2011''');<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br><br />
<br />
'''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''<br><br />
abstract: <br><br />
Selected refs:<br />
<br />
===[http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) ===<br />
'''勾配情報が作り出す発生メカニズム'''<br><br />
<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol''. ('''2014'''); Peluso et al. ''Dev. Cell'' ('''2011'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br><br />
<br />
'''Double bladed aspect of gene recruitment to morphological evolution.'''<br><br />
abstract: <br><br />
Selected refs: Wang et al. Nat. Genetics (2013); Irie and Kuratani. Nat. Commun. (2011)<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br><br />
<br />
'''Linking quantities from information to fitness'''<br><br />
abstract: <br><br />
Selected refs: Kobayashi and Sughiyama. PRL (2015); Kobayashi. PRL (2011); Kobayashi. PRL (2010)<br />
<br><br />
<br><br />
<br><br />
<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=4984SpeakersandAbstracts2015-12-13T07:29:28Z<p>Noriko.hiroi: /* 'How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly? */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development. <br />
<br><br />
This work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara. <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement.<br />
<br><br />
This work is done in collaboration with K. Ikawa.<br />
<br><br />
<br><br />
Selected refs: Guirao et al. eLife, ''in press''; Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs: Sumiyoshi et al. Front Physiol. (2015); Hiroi et al. Front Physiol. (2014)<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br><br />
<br />
'''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''<br ><br />
abstract: <br><br />
Selected refs: Samarage et al. Dev. Cell (2015); Fierro-González et al. Nat. Cell Biol. (2013); Plachta et al. Nat. Cell Biol. (2011)<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
title: tba<br ><br />
abstract: <br><br />
Selected refs: Fukuyama et al. Langmuir (2015); Maeda et al. PNAS (2012); Maeda et al. PRL (2011)<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?'''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br><br />
<br />
'''Dissecting neural circuits for motion estimation in Drosophila'''<br><br />
abstract: <br><br />
Selected refs: Fitzgerald and Clark. eLife (2015); Clark et al. Nat. Neurosci. (2014); Clark et al. Neuron (2011);<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br><br />
<br />
'''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''<br><br />
abstract: <br><br />
Selected refs:<br />
<br />
===[http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) ===<br />
'''勾配情報が作り出す発生メカニズム'''<br><br />
<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol''. ('''2014'''); Peluso et al. ''Dev. Cell'' ('''2011'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br><br />
<br />
'''Double bladed aspect of gene recruitment to morphological evolution.'''<br><br />
abstract: <br><br />
Selected refs: Wang et al. Nat. Genetics (2013); Irie and Kuratani. Nat. Commun. (2011)<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br><br />
<br />
'''Linking quantities from information to fitness'''<br><br />
abstract: <br><br />
Selected refs: Kobayashi and Sughiyama. PRL (2015); Kobayashi. PRL (2011); Kobayashi. PRL (2010)<br />
<br><br />
<br><br />
<br><br />
<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=SpeakersandAbstracts&diff=4983SpeakersandAbstracts2015-12-13T07:29:10Z<p>Noriko.hiroi: /* Akatsuki Kimura ( National Insititute of Genetics, Japan ) */</p>
<hr />
<div>==Speakers and Abstracts==<br />
We have brought together researchers who have the potential to take the lead in quantitative biology as next-generation leaders. <br><br />
次世代のリーダーとして定量生物学を牽引していくポテンシャルを有する研究者が揃っています。大御所を並べただけではない、定量生物学の会ならではの講演者のラインナップになっております。<br />
<br />
==Session: Quantity - FORCE -==<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
<br />
===[http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )===<br />
'''油滴を利用して、生体組織の力学を"その場で"測る。'''<br><br />
<br />
===='''Quantifying tissue mechanics in vivo and in situ'''====<br />
Mechanical cues play a critical role during tissue morphogenesis and organ formation in the embryo. Despite their relevance in sculpting functional embryonic structures, very little is known about the mechanisms by which tissue mechanics affects/controls developmental processes, mainly because it has not been possible to quantify tissue mechanics within developing tissues in vivo. In this talk, I will present two new techniques that permit direct quantification of (1) cell-generated mechanical forces and (2) the mechanical properties of the cellular microenvironment, in situ within living tissues and developing organs. Using these novel techniques, we quantify the cell-generated mechanical stresses and the local mechanical properties within cell aggregates, living mouse mandibles and live zebrafish embryos.<br />
<br><br />
<br><br />
Selected refs: Campàs et al. ''Nat. Methods'' ('''2014'''); Campàs et al. ''BPJ'' ('''2012'''); Campàs et al. ''PNAS'' ('''2010''')<br />
<br />
===[http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto University, Japan )===<br />
'''ベイズ統計学をつかって、見えない力を見る。アクチン結合タンパク質の力生成能と力感知能に注目して、形態形成の力学制御の分子メカニズムに迫る。'''<br><br />
<br />
===='''Dissecting the mechanical control of Drosophila wing shape determination'''====<br />
Tissues acquire their unique shape and size through a series of deformations. Tissue deformation consists of changes in cell shape, number, and position, which are triggered by forces acting between cells and by biochemical signaling. Reciprocal feedback is present at and among the molecular, cellular, and tissue scales. We sought to clarify the emergence of the Drosophila wing shape from these multi-scale feedback regulations. In the symposium, I shall discuss our ongoing research on the unified quantification of epithelial tissue development and molecular dissection of force sensing/generation by F-actin during directional cell rearrangement.<br />
<br><br />
1. Quantifying tissue mechanics and kinematics in an integrated way<br />
We have developed and validated key techniques to quantify the multi-scale dynamics underlying wing shape determination, including Bayesian force inference, whole-wing imaging, and texture tensor formalism (Ishihara and Sugimura, 2012; Ishihara et al., 2013; Sugimura et al., 2013; Guirao et al., 2015). By analyzing space-time maps of tissue deformation, tissue stress, and cell dynamics in control and mutant tissues, we evidenced unexpected interplays between patterns of tissue elongation, cell division and stress. Our methods provide a basis for comprehensive analyses of mechanical control of epithelial tissue development. <br />
<br><br />
This work is done in collaboration with F. Graner, Y. Bellaïche, B. Guirao, S. Rigaud, P. Marcq, and S. Ishihara. <br />
<br><br />
2. Dissecting molecular mechanism of extrinsic force-driven cell rearrangement<br />
During tissue morphogenesis, cells change their relative positions along the tissue axis by remodeling cell contact surfaces. This process, called directional cell rearrangement, shapes a tissue and develops its multi-cellular pattern. In the Drosophila pupal wing, anterior-posterior cell contact surfaces shrink and are remodeled to form new proximal-distal cell contact surfaces from 21 hr APF onwards. We previously reported that the extrinsic stretching force provides directional information for assignment of the orientation of cell rearrangement, leading to tissue elongation and hexagonal cell packing (Sugimura and Ishihara, 2013). However, the mechanisms by which cells sense the extrinsic forces and transmit the information to the molecular machinery for cell rearrangement remain unknown. To answer these questions, we performed screening of actin-binding proteins. Our results suggest that AIP1, cofilin, and coronin-1 regulate F-actin to trigger the extrinsic force-driven cell rearrangement.<br />
<br><br />
This work is done in collaboration with K. Ikawa.<br />
<br><br />
<br><br />
Selected refs: Guirao et al. eLife, ''in press''; Sugimura and Ishihara. ''Development'' ('''2013'''); Ishihara and Sugimura. ''J. Theor. Biol.'' ('''2012''')<br />
<br />
===[http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )===<br />
'''原腸形成過程は進化的に広くみられるが、コアとなる誘導シグナルははっきりしていなかった。それがなんと機械的応力である可能性が示された。'''<br><br />
<br />
===='''From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction'''====<br />
Bilaterians are complex organisms, characterized by the existence of a mesoderm tissue from which most of animal complex organs develop. Mesoderm emerged 570 millions years ago from cnidarians that are characterized by and ectoderm and an endoderm only. The lack of conservation of biochemical signalling proteins upstream of early embryonic mesoderm differentiation across bilaterians prevents to answer the question of the signal having been at the origin evolutionary origin of mesoderm emergence and complex animals. Here we found the mechano-transductive phosphorylation of the Y654 site of β-catenin by the first morphogenetic movements of embryogenesis, leading to its release into the cytoplasm and nucleus, as involved and conserved in earliest mesoderm differentiation in the vertebrate zebrafish and un-vertebrate Drosophila, two species having directly diverged from the last common ancestor of bilaterians. We proposed mechanical activation of β-catenin signalling as having initiated the evolutionary transition to mesoderm differentiation and complex animals evolutionary emergence[1].<br />
<br><br />
We additionally find mechanical activation of β-catenin as involved in the mechanical activation of tumorogenic biochemical pathways, in the healthy epithelium compressed by the neighbouring tumour, in response to tumour growth pressure ''in vivo'' [2-4].<br />
<br><br />
<br><br />
1 Brunet, T. et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nature communications 4, doi:10.1038/ncomms3821 (2013).<br><br />
2 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon. HFSP journal 2, 286-294, doi:10.2976/1.2955566 (2008).<br><br />
3 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of the tumorogenic β-catenin pathway by tumour growth pressure. Nature, 10.1038/nature14329 (2015).<br><br />
4 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. Mechanotransduction's Impact in Animal Development, Evolution, and Tumorigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio-102314-112441 (2015). <br><br />
<br><br />
Background : soft matter biophysics, developmental biology<br />
Websites : http://cvscience.aviesan.fr/cv/818/emmanuel-farge, http://umr168.curie.fr/en/Farge-group<br />
<br><br />
<br><br />
Selected refs: Fernández-Sánchez et al. ''Nature'' ('''2015'''); Brunet et al. ''Nat. Commun''. ('''2013'''); Farge. ''Curr. Biol''. ('''2003''')<br />
<br />
==Session: Quantity - SYMMETRY I -==<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
<br />
===[http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )===<br />
<br><br />
<br />
'''Anisotropy shaped by and for the dynamic distribution of heat'''<br ><br />
abstract: <br><br />
Selected refs: Sumiyoshi et al. Front Physiol. (2015); Hiroi et al. Front Physiol. (2014)<br />
<br />
===[http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )===<br />
'''マウス初期胚の対称性の破れに定量イメージングで迫る'''<br><br />
<br />
'''Seeing how mammalian life starts: Quantitative imaging in live mouse embryos'''<br ><br />
abstract: <br><br />
Selected refs: Samarage et al. Dev. Cell (2015); Fierro-González et al. Nat. Cell Biol. (2013); Plachta et al. Nat. Cell Biol. (2011)<br />
<br />
===[http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )===<br />
'''構成的手法から探る生命システムの構築原理:生命の起源と人工細胞のダイナミクス'''<br><br />
<br />
title: tba<br ><br />
abstract: <br><br />
Selected refs: Fukuyama et al. Langmuir (2015); Maeda et al. PNAS (2012); Maeda et al. PRL (2011)<br />
<br />
===[http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )===<br />
'''マグネトジェネティクス:情報流れの時空間制御が明らかにする自己組織化の原理'''<br ><br />
<br />
===='''Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools'''====<br />
Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools<br />
<br><br />
The cytoskeleton is essential for the function of cellular processes such as cell division and cell migration. Cytoskeleton fibers participate in the maintenance of cell internal organization and play essential roles in breaking symmetry and establishing cell polarity.<br />
We have developed an in vitro system capturing the spatial organization of cytoskeleton filaments within a geometry that mimic the cellular environment. This system, based on the cellular reconstitution by confinement of Xenopus cytoplasmic extracts, is used to examine simple aspects of symmetry breaking. <br><br />
(1) We will first discuss how geometrical confinement and mechanical properties influence the self-organization of microtubules and molecular motors.,br><br />
(2) In most physiological situations, the asymmetric fate of a system follow from certain “cues” that pre-exist before symmetry is broken. These cues are either localized signals often encoded in protein concentration gradients, or “landmarks” inherited from the system’s history. For instance, gradients of signaling proteins and protein localization can be key for cell-fate decision and asymmetric cell division. In order to control the spatiotemporal localizations of these cues, we are using magnetic nanoparticles to spatially localize signaling proteins within confined extracts. This system is used to examine how the spatial localization and clustering of RCC1/RanGTP proteins feedbacks on microtubule spatial organization.<br />
<br><br />
<br><br />
Selected refs: Hoffmann et al. ''Nat. Nanotech''. ('''2013'''); Pinot et al. ''PNAS'' ('''2012''').<br />
<br />
==Session: Quantity - SYMMETRY II -==<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
<br />
===[http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )===<br />
'''Cliff Brangwynne博士は物理学の視点から細胞生物学に新しいコンセプトを導入し、近年、大きなインパクトを与えて続けている新進気鋭の研究者です。「相転移/phase transition」は、例えば水分子が沸点や融点をまたぐと固体、液体、気体と急激に状態を変化させるような物理学のコンセプトです。Brangwynne博士は、細胞内で核小体や生殖顆粒が形成・消滅する過程を、この相転移現象として理解できることを明らかにしています。'''<br><br />
<br />
===='''Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles'''====<br />
RNP bodies are RNA and Protein-rich, membraneless organelles that play important roles in regulating gene expression. The largest and most well-known nuclear RNP body is the nucleolus, whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets. Increasing evidence suggests they condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid–liquid phase separation. We combine ''in vivo'' and ''in vitro'' experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of “extranucleolar droplets” (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C.elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can<br />
modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism.<br />
<br><br />
<br><br />
selected refs: Berry et al. ''PNAS'' ('''2015'''); Feric and Brangwynne. ''Nat. Cell Biol''. ('''2013'''); Brangwynne et al. ''Science'' ('''2009''')<br />
<br />
===[http://www.nig.ac.jp/labs/CelArchi/cell_archi_home.html '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )===<br />
'''多数の小さな分子たちによってどのように細胞レベルでの空間的な秩序ができるのかを研究しています。本発表では、線虫C. elegansの細胞質流動を例に、流れの方向が定まらない(不安定)流動が、必ず(安定的に)生じるメカニズムについて発表します。'''<br />
<br />
===='''How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?''====<br />
In this presentation, I will present our recent research on a symmetry breaking event observed in the early embryo of Caenorhabditis elegans. Cytoplasmic streaming is a cell-wide flow occurring in various plants and animals. In C. elegans, the streaming of ooplasm is observed upon fertilization. As the polarity of the zygote is not established at this stage, the direction of the cell-wide flow is not pre-determined, but determined in a self-organized manner. Interestingly, the direction of the flow changes during the streaming. Using a quantitative live-cell imaging, we characterized the dynamics of the flow, and proposed a mechanism for the self-organization of the flow. The proposed mechanism was tested using a theoretical modeling. I will discuss the applicability of our model on cytoplasmic streaming in general. <br />
<br><br />
<br><br />
selected refs: Kimura and Kimura. ''J. Cell Sci''. ('''2012'''); Niwayama et al. ''PNAS'' ('''2011'''); Kimura and Kimura. ''PNAS'' ('''2011''')<br />
<br />
===[http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )===<br />
'''細胞のミクロとマクロを定量的 in vivo イメージングでつなぐ:細胞内アクチン動態・張力から細胞の巨視的挙動へ'''<br><br />
<br />
===='''Intercellular forces orchestrate contact inhibition of locomotion'''====<br />
Contact Inhibition of locomotion (CIL), a process where migrating cells repel upon collision, was first observed in cultured cells more than 60 years ago. We have recently revealed that Drosophila hemocytes have precise CIL interactions in vivo, which lead to their subsequent developmental patterning. To quantify the dynamics of collisions we have recently developed techniques to analyze the exact velocity and acceleration changes surrounding the contact inhibition process. This analysis has revealed rapid and synchronous kinematic changes (over second timescales) during collisions, which further highlight the precision of the CIL response.<br />
<br><br />
To examine the cause of such intriguing CIL kinematics we have examined the actin network dynamics surrounding collisions. We adapted a pseudo-speckle microscopy technique to track the retrograde flow dynamics of the actin cytoskeleton during hemocyte developmental dispersal. Non-colliding cells show rapid retrograde flow (3-4μm/min), which moves centripetally towards the cell body where actin flow significantly decreases. Analysis of collisions reveals that the actin flow undergoes significant temporal and spatial reorganization across the entire lamella, which occurs simultaneously in colliding partners. A region of low retrograde flow develops perpendicular to the leading edge spanning colliding cells, and upon repulsion, retrograde flow simultaneously spikes in both lamellae. These dynamics suggest that hemocytes are becoming transiently coupled during CIL via a clutch-like mechanism, analogous to the integrin clutch encountered in migrating cells.<br />
<br><br />
Exploiting the precise retrograde flow displacements, we subsequently modelled the cytoskeletal stresses in freely moving and colliding cells using a linear viscoelastic model. Preliminary results show that non-colliding cells have high regions of network stress surrounding the cell body, explaining the convergence of the retrograde flow within this region. Upon collision, forces are redistributed from the cell body to the leading edge along the region of low retrograde flow. This region of stress becomes decorated with myosin II suggesting the development of a transient stress fiber as colliding cells pull on each other during the collision. We speculate that this “haptic feedback” mechanism, and subsequent release of lamellar tension, explains the precise and synchronous nature of the contact inhibition response. <br />
<br><br />
<br><br />
Selected refs: Davis et al. ''Cell'' ('''2015'''); Davis et al. ''Development'' ('''2012'''); Stramer et al. ''J. Cell Biol''. ('''2010''')<br />
<br />
==Session: Quantity - INFORMATION -==<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
<br />
===[http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )===<br />
===='''Revisiting cell migration mechanisms of crawling cells'''====<br />
In the social amoebae Dictyostelium discoideum, stimulation by chemoattractant cAMP invokes a transient rise in cytosolic cAMP that is secreted to excite other cells in the neighborhood. Aggregation of Dictyostelium cells is dictated by chemotaxis towards traveling waves of cAMP that self-organize in the cell monolayer. Because reversal of spatial gradient occurs after every passage of wavefronts, it is unclear why the cells do not fall into a futile cycle of back and forth movement. This is the so-called ‘chemotactic wave paradox’. By employing a microfluidics-based flow focusing, we have recently demonstrated that small guanosine triphosphatase (GTPase) Ras activation at the leading edge is suppressed when the chemoattractant concentration is decreasing over time. This ‘rectification’ of directional sensing is optimal for wave passage time of ~6min and the overall features can be fully recapitulated by a mathematical model that describes an adaptive leading edge response that is localized in space by a global inhibitory signal. In the talk, we will present some of our recent findings in the related collective migratory behaviors as well as some of the common features found in immune cells.<br />
<br><br />
<br><br />
Selected refs: Nakajima et al. ''Nat. Commun''. ('''2014'''); Taniguchi et al. ''PNAS'' ('''2013'''); Gregor et al. ''Science'' ('''2010''')<br />
<br />
===[http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )===<br />
'''ショウジョウバエの視覚神経回路:動きを読みだす情報処理に迫る定量生物学'''<br><br />
<br />
'''Dissecting neural circuits for motion estimation in Drosophila'''<br><br />
abstract: <br><br />
Selected refs: Fitzgerald and Clark. eLife (2015); Clark et al. Nat. Neurosci. (2014); Clark et al. Neuron (2011);<br />
<br />
===[http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )===<br />
'''定量と再構築から理解する感覚神経細胞の環境認識'''<br><br />
<br />
'''Quantification and reconstruction of thermosensory neuronal processing in C. elegans'''<br><br />
abstract: <br><br />
Selected refs:<br />
<br />
===[http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) ===<br />
'''勾配情報が作り出す発生メカニズム'''<br><br />
<br />
===='''Quantification and modeling of BMP signaling during zebrafish embryo development'''====<br />
Bone Morphogenetic Proteins (BMPs) act in developmental pattern formation as a paradigm of extracellular information that is passed from an extracellular morphogen to cells that process the information and differentiate into distinct cell types based on the morphogen level. In addition to their role in development, BMPs play an important role in tissue homeostasis and mutations in the BMP family are associated with a number of human cancers. Numerous extracellular modulators and feedback regulators establish and control the BMP signaling distribution along the dorsal-ventral (DV) embryonic axis in vertebrates to induce space and time-dependent patterns of gene expression. To identify how the dynamic pattern is regulated during development, we have developed a seamless data-to-model integration and optimization strategy. First, the nuclear intensities of fluorescent stained Phosphorylated-Smad5 (P-Smad) are acquired for each nuclei in each embryo from staged populations to provide a quantitative time-course for the BMP signaling gradient. Next, the nuclei are segmented to yield quantitative point-clouds of P-Smad level at each nuclei. The individual point clouds are registered to similarly staged embryos using a process called Coherent Point Drift (CPD) and the registered populations provide rigorous quantification and comparison of phenotype. To delineate the mechanism of BMP signal inhibition by the secreted binding proteins Chordin (Chd), Noggin (Nog), and Follistatin (Flst), a mathematical model was developed and optimized against the population data for wild type and combinations of the Chd mutants with and without morpholino knockdown of Noggin and Follistatin. We found a model that reproduced the experimentally observed reliability of the patterning network for Chd LOF, and for Nog/Flst morpholino knockdown that was also consistent with the dramatic increase in signaling observed in Chd LOF, Nog/Flst knockdown. Models consistent with experimental behavior require that Chordin has a greater range than Noggin, that Noggin is not freely diffusible, and that Noggin rapidly binds available BMP ligands in the organizer region. We are continuing to experimentally test the model predictions and isolate the roles of Noggin and Follistatin to determine the extent of dorsal enrichment under different conditions.<br />
<br><br />
<br><br />
Selected refs: Pargett et al. ''PLoS Comp. Biol''. ('''2014'''); Peluso et al. ''Dev. Cell'' ('''2011'''); Umulis et al. ''Dev. Cell'' ('''2010''')<br />
<br />
==Session: Quantities and Beyond -==<br />
Date and Time: Jan. 11th 9:00-11:00<br><br />
<br />
===[http://www.biol.s.u-tokyo.ac.jp/users/hassei/English/ '''Naoki Irie''']( the University of Tokto, Japan )===<br />
'''胚発生と進化の法則性として近年支持された砂時計モデル。この法則性を生み出すメカニズムの有力候補がみえてきた。'''<br><br />
<br />
'''Double bladed aspect of gene recruitment to morphological evolution.'''<br><br />
abstract: <br><br />
Selected refs: Wang et al. Nat. Genetics (2013); Irie and Kuratani. Nat. Commun. (2011)<br />
<br />
===[http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )===<br />
'''1細胞ヒストリーの観点から適応度と遺伝子発現を捉え直す'''<br><br />
<br />
===='''Fitness and gene expression from the viewpoint of single-cell histories'''====<br />
Growth and division of cells require interplay of large numbers of intracellular molecular species. An amount of each molecular species in a single cell such as protein and RNA is variable among different individual cells and in time-course, which results in cellular growth noise. In this talk, we address two important questions regarding cellular growth noise both theoretically and experimentally: (1) How does growth noise at the cellular level affect population growth properties? (2) How can we quantitatively reveal the effect of noise at the molecular level on cellular reproduction ability? To answer the first question, we carried out large-scale single-cell time-lapse measurements on clonal proliferation processes of Escherichia coli in constant environments with a custom microfluidic device. The results show that clonal population of E. coli grow faster than the constituent single cells under diverse balanced-growth conditions. We reveal that the observed growth rate gain at the population level is strongly correlated with cellular growth noise strength and quantitatively predictable from the equation that connects generation time distribution and population growth rate. Furthermore, we prove that growth rate gain is directly linked to statistical deviation between two types of generation time distribution along chronological and retrospective cell histories. To address the second question, we developed a statistical method that allows us to measure fitness landscape and selection strength for heterogeneous phenotypic states, employing a conceptual framework to regard cell history as a unit of proliferation. We analyzed single-cell time-lapse data of E. coli that expresses streptomycin resistance gene (smR) in the presence of sub-inhibitory concentration of streptomycin. The result suggests that the role of smR against drug exposure is better represented by protein production rate than protein concentration. These measurements demonstrate the utility of cell history-based viewpoint in single-cell analysis, and raise a question as to the interpretation on the role of gene expression level at the cellular level. <br />
<br><br />
<br><br />
Selected refs: Wakamoto et al. ''Science'' ('''2013'''); Wakamoto et al. ''Evolution'' ('''2012'''); Tomita et al. ''Langmuir'' ('''2011''')<br />
<br />
===[http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )===<br />
'''「量」をつなぐ:情報から適応度まで'''<br><br />
<br />
'''Linking quantities from information to fitness'''<br><br />
abstract: <br><br />
Selected refs: Kobayashi and Sughiyama. PRL (2015); Kobayashi. PRL (2011); Kobayashi. PRL (2010)<br />
<br><br />
<br><br />
<br><br />
<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br></div>Noriko.hiroihttp://131.113.63.82/index.php?title=IIS_Sympo&diff=4982IIS Sympo2015-12-13T07:27:42Z<p>Noriko.hiroi: /* Session: Quantity - SYMMETRY II - */</p>
<hr />
<div>=='''NIG International Symposium 2016'''==<br />
This event is sponsored by National Institute of Genetics ([http://www.nig.ac.jp/nig/ NIG]) and held as the NIG International Symposium 2016.<br />
<br />
===''Tokyo Symposium at Institute of Industrial Science, the University of Tokyo''===<br />
<br />
=='''Force, Information and Dynamics: X factors shaping living systems '''==<br />
<br />
<span style="color: green">'''Exploring frontiers of quantitative biology by identifying X-factors that shape living systems'''</span><br />
<br />
'''Quantitative biology is a growing discipline goes beyond the quantification of biological phenomena and attempts to unveil fundamental and general principles governing living systems.'''<br />
<br />
'''After decades of emphasis on the study of GENES to reveal such principles, recent advances in quantitative biology have shed light on other key factors in biology, designated as X-FACTORS. X-factors include FORCE and SYMMETRY, which control the shape, size, and movement of cells and tissues, and INFORMATION, which characterizes processing and transduction of intra- and inter-cellular signaling. Enumerating such X-factors represents a milestone in quantitative biology.'''<br />
<br />
'''In the Tokyo Symposium, we shall focus on X-factors in biology. This symposium was designed to share and discuss our vision for the frontiers of quantitative biology with cutting-edge researchers from around the world. We expect active discussions on state-of-the-art techniques to measure and manipulate X-factors and on the integration of different X-factors, leading towards a deeper understanding of the nature of living systems.'''<br />
<br />
==Date: Jan 9th - 11th, 2016.==<br />
Jan. 9th 13:00 to Jan. 11th 12:00<br />
<br />
==Venue for workshops and the Symposium at Tokyo==<br />
Convention hall, An Block, Institute of Industrial Science, <br/><br />
Komaba Ⅱ Research Campus, the University of Tokyo.<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/access_e.html Access to Komaba Ⅱ Research Campus]<br />
<br/>[http://www.iis.u-tokyo.ac.jp/access_e/campusmap_e.html Campus map]<br />
<br />
==Registration is '''OPEN'''(Dec/10/2015)==<br />
'''Registration from [https://docs.google.com/forms/d/1hNiBiiLu73N0Mo9FS5O03D0LTu7VHHP-BqJtOAzoNPY/viewform?usp=send_form here].'''<br><br />
'''Please be sure that the above registration and abstract submission are both ONLY for Tokyo Symposium. '''<br />
<br/>For the registration and abstract submission to the other workshops and symposium, you may visit the other sites ([http://q-bio.jp/wiki/Events Events]).'''<br />
Seating capacity: Approximately 150, excluding invited speakers ( approx. 20 people ).<br />
<br/><br />
==Poster Abstract submission deadline: Dec. 10th thr. 2015<br>== <br />
'''For a poster presentation, please submit your abstract from [https://docs.google.com/forms/d/1x3dNWPk6GZDBLec_O3WFCaXsaqmis83wtzdt8f5AetM/viewform?usp=send_form here].'''<br />
<br/><br />
''After the deadline, we will still open the opportunity for poster presentation. Please feel free to submit your abstract and bring your poster''.<br><br />
''In case it will take a time to include the late posters into abstract booklet.''<br />
<br><br />
==Poster Size (Dec/10/2015)== <br />
The size of a poster panel is w 1130[mm] × h 1630[mm].<br/><br />
Standard <span style="color: red">A0</span> (841[mm]×1189[mm]) or <span style="color: red">B0</span> (1030[mm]×1456[mm]) size poster is recommended.<br />
<br/><br />
<br/><br />
<span style="color: red">When you are planning to bring the same poster to Mishima Symposium, <br />
<br><br />
A0 size poster should be fine.</span><br />
<br/><br />
<br/><br />
<br />
==Speakers and Abstracts==<br />
[[SpeakersandAbstracts|<span style="color: red">'''Link to a "Speakers and Abstracts" page.'''</span>]]<br />
<br />
==Scientific Program==<br />
=== Jan. 9th===<br />
-----<br />
=====Opening Remarks=====<br />
Date and Time: Jan. 9th 13:00-13:10<br><br />
-----<br />
<br />
====Session: Quantity - FORCE -====<br />
Date and Time: Jan. 9th 13:10-15:25<br><br />
Chair: '''Kaoru Sugimura'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://me.ucsb.edu/people/otger-campas '''Otger Campàs'''] ( University of California, Santa Barbara, USA )<br><br />
title: "Quantifying tissue mechanics in vivo and in situ"<br />
|-<br />
!<br />
!<br />
![http://www.koolau.info/ '''Kaoru Sugimura'''] ( Kyoto Univ., Japan )<br><br />
title: "Dissecting the mechanical control of Drosophila wing shape determination"<br />
|-<br />
!<br />
!<br />
![http://umr168.curie.fr/en/profile/emmanuel-farge-00906 '''Emmanuel Farge'''] ( Institut Curie, France )<br />
title: "From mesoderm mechanotransductive evolutionary origins to tumourogenic mechanical induction"<br />
|-<br />
|}<br />
<br />
====Poster Session I====<br />
Date and Time: Jan. 9th 15:25-18:30 including 5-min instructions of poster presentations<br><br />
<br />
----<br />
----<br />
<br />
=== Jan. 10th===<br />
-----<br />
====Session: Quantity - SYMMETRY I -====<br />
Date and Time: Jan. 10th 9:00-12:00<br><br />
Co-Chair: '''Noriko Hiroi and Yusuke Maeda'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://fun.bio.keio.ac.jp/people/ '''Noriko Hiroi'''] ( Keio University, Japan )<br />
title: "Anisotropy shaped by and for the Dynamic Distribution of Heat"<br />
|-<br />
!<br />
!<br />
![http://www.imcb.a-star.edu.sg/php/np.php '''Nicolas D Plachta'''] ( IMCB, Singapore )<br />
title: "Seeing how mammalian life starts: Quantitative imaging in live mouse embryos"<br />
|-<br />
!<br />
!<br />
![http://www.yusukeman.org/YM/youkoso.html '''Yusuke Maeda'''] ( Kyushu University, Japan )<br />
title: tba<br />
|-<br />
!<br />
!<br />
![http://www.chimie.ens.fr/?q=en/umr-8640/biophysical-chemistry/profil/zoher.gueroui '''Zoher Gueroui'''] ( École Normale Supérieure, France )<br />
title: "Studying cytoskeleton symmetry breakings using cellular reconstitution of cytoplasmic extracts and biophysical tools"<br />
|-<br />
|}<br />
<br />
====Poster Session II====<br />
Date and Time: Jan. 10th 12:00-13:30<br><br />
<br><br><br />
----<br />
<br />
====Session: Quantity - SYMMETRY II - ====<br />
Date and Time: Jan. 10th 13:30-15:45<br><br />
Chair: '''Akatsuki Kimura'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://www.princeton.edu/cbe/people/faculty/brangwynne/ '''Cliff Brangwynne'''] ( Princeton University, USA )<br><br />
title: "Measuring the Intracellular Dew Point: The Physics and Biology of Membrane-less Organelles"<br />
|-<br />
!<br />
! <br />
![http://www.nig.ac.jp/nig/research/interviews/faculty-interviews/kimura '''Akatsuki Kimura'''] ( National Insititute of Genetics, Japan )<br><br />
title: "How a cell-wide cytoplasmic flow with unstable direction emerges reproducibly?"<br />
|-<br />
!<br />
! <br />
![http://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/stramer/stramerbrian.aspx '''Brian Stramer'''] ( King's College London, UK )<br />
title: "Intercellular forces orchestrate contact inhibition of locomotion"<br><br />
|}<br />
<br><br />
----<br />
'''Coffee Break'''<br />
Date and Time: Jan. 10th 15:45-16:00<br><br />
----<br />
<br />
====Session: Quantity - INFORMATION -====<br />
Date and Time: Jan. 10th 16:00-19:00<br><br />
Chair:'''Yuki Tsukada'''<br><br />
Speakers:<br />
{|<br />
|-<br />
!<br />
! <br />
![http://sawailab.c.u-tokyo.ac.jp/# '''Satoshi Sawai'''] ( the University of Tokyo, Japan )<br><br />
title: "Revisiting cell migration mechanisms of crawling cells"<br />
|-<br />
!<br />
! <br />
![http://clarklab.yale.edu/ '''Damon Clark'''] ( Yale University, USA )<br />
title: "Dissecting neural circuits for motion estimation in Drosophila"<br />
|-<br />
|-<br />
!<br />
!<br />
![http://elegans.bio.nagoya-u.ac.jp/~tsukada/ '''Yuki Tsukada'''] ( Nagoya University, Japan )<br />
title: "Quantification and reconstruction of thermosensory neuronal processing<br />
in C. elegans"<br />
|-<br />
!<br />
!<br />
![http://engineering.purdue.edu/ABE/People/ptProfile?resource_id=46484 '''David Umulis'''] ( Purdue University, USA ) <br />
title: "Quantification and modeling of BMP signaling during zebrafish embryo development "<br />
|}<br />
----<br />
<br />
====Mixer at the poster presentation Hall====<br />
Date and Time: Jan. 10th 19:00-20:30<br><br />
<br><br><br />
----<br />
----<br />
<br />
=== Jan. 11th===<br />
-----<br />
====Session: Quantities and Beyond====<br />
Date and Time: Jan. 11th 9:00-11:15<br><br />
Chair: '''Naoki Irie'''<br><br />
Speakers:<br />
{|-<br />
!<br />
! <br />
![http://www.biol.s.u-tokyo.ac.jp/users/hassei/irie/index_e.html '''Naoki Irie''']( the University of Tokto, Japan )<br />
title: "Double bladed aspect of gene recruitment to morphological evolution"<br />
|-<br />
!<br />
!<br />
![http://park.itc.u-tokyo.ac.jp/wakamoto-lab/Member_e.html '''Yuichi Wakamoto'''] ( the University of Tokyo, Japan )<br />
title: "Fitness and gene expression from the viewpoint of single-cell histories"<br />
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!<br />
!<br />
! [http://research-en.crmind.net/ '''Tetsuya J Kobayashi''']( the University of Tokyo, Japan )<br />
title: "Linking Quantities from Information to Fitness"<br />
|}<br />
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====Open Discussion====<br />
Date and Time: Jan. 11th 11:15-12:00<br><br />
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==Links==<br />
[http://q-bio.jp/wiki/IIS_Sympo Tokyo Symposium: Force, Information and Dynamics: X factors shaping living systems]<br><br />
[http://symposium.crmind.net/bridging_thr_exp/Home.html NIG International Symposium 2016 satellite workshop]<br> <br />
[http://symposium.crmind.net/EIC2015/Home.html Toyota Physical & Chemical Research Institute Workshop] <br><br />
[http://www.nig.ac.jp/labs/CelArchi/nigsymposium2016/MishimaSympo.html Mishima Symposium: Quantitative Biology - force, information and dynamics]<br><br />
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==Contacts==<br />
qbioint2016 at gmail.com<br><br />
<br><br />
Organizers: Akatsuki Kimura (NIG), Akira Funahashi (Keio Univ.), Noriko F. Hiroi (Keio Univ.), Tetsuya J. Kobayashi (Univ. Tokyo)<br><br />
<br><br />
Program committee: Kaoru Sugimura (Kyoto Univ.), Yuki Tsukada (Nagoya Univ.), Naoki Irie (Univ. Tokyo), Junnosuke Teramae (Osaka Univ), Yusuke Maeda (Kyushu Univ.)</div>Noriko.hiroi