Update


2022/8/26
Announcement of Publicly Offered Research Online Briefing Session(*Please see Call for Publicly Offered Research proposal for details.)


2022/08/01 
Call for Publicly Offered Research proposal is now open. (*Please see Call for Publicly Offered Research proposal for details.)


2022/08/01 
Website is now available.



Research Theme

Elucidating the design principles of multicellular organisms is a fundamental challenge for researchers in the field of life science. Global order of an organism generally develops from local interactions among molecules and cells. Collectively, these interactions – referred to as self-organization – give rise to the emergent properties of fate, form, and function of cells, ultimately leading to the morphogenesis of tissues and organs. Mechanical forces that cause changes in size, shape, and position of cells are integral to morphogenesis. Recent studies highlighted the potential for mechanical forces to modulate cellular fate and function, suggesting the existence of complex feedbacks between forces and cellular physiology.

The research project that we propose for the Grants-in-Aid for Transformative Research Areas (A) aims to develop new paradigms for morphogenesis through a quantitative and holistic evaluation of how mechanical forces control the emergent properties of self-organizing feedbacks in the developing organisms. We will develop cutting-edge technologies to visualize the mechanical processes, and quantify the magnitude and distribution of forces both within cells and in the extracellular spaces. With this insight, we will be able to understand how forces elicit self-organizing feedbacks to orchestrate progressive self-tuning and transformation of multicellular systems over long timescales. This will shed light on the design principles underlying the interplay between tissue mechanics with gene expression, how these principles arise during development, and how their malfunction leads to aging and disease.

The scientists within this research team includes experts in biomedical sciences, engineering, mathematics, and physics. The unique infrastructure – in particular, the state-of-the-art core facilities for diverse technologies – will facilitate organic collaboration between researchers in the diverse fields of basic science and engineering. We will push the frontiers of life science research to explore the physical basis of living systems.

Message from the Research Director

An embryo produces cells with specific fates, forms, and functions. The developmental processes involved require collective interactions of biological components, which give rise to an ordered state in space and time. The concept of “self-organization” is widely recognized as a core principle in pattern formation, but the mechanisms underlying multicellular morphogenesis are only beginning to be elucidated. Historically, the process has been considered to be a cascade of activities, beginning with the triggering of gene expression and progressing through to the changes in cellular morphology. However, morphogenesis is increasingly viewed as a self-organizing process governed by feedback between fate, cell polarity, geometry, and mechanical forces.

The team of scientists in this Grants-in-Aid for Transformative Research Areas (A) project aims to develop new paradigms for morphogenesis through a quantitative and holistic evaluation of how mechanical forces of cells and tissues control the emergent properties governing self-organizing feedback during development. Our team is composed of three sub-groups: A01 and A02 will elucidate the mechanical self-organization in a diverse array of multicellular systems; B01 will develop novel techniques for the measurement and manipulation of mechanical forces, as well as theoretical methods for modeling and numerically simulating self-organization. With the cutting-edge technologies needed to interrogate the mechanical processes, we will establish a unique model for multi-disciplinary research that harnesses expertise from diverse fields. We welcome investigators in biomedical sciences, engineering, mathematics, physics, and chemistry to join us.

Fumio Motegi
Hokkaido University


Team

A01

Self-organization of multi-cellular systems by mechanical forces within cells

Elucidate how “forces generated by cells” orchestrate cell-to-cell communication in the self-organization process of living organisms.


A01-1
Mechanical control of germ-soma dichotomy in embryogenesis

This research focuses on critical early decision during embryogenesis, such as the determination of embryonic polarity and whether a cell becomes a somatic or germline cell. We will employ tools and techniques needed to interrogate the mechanical processes to analyze how embryonic patterning is regulated by coupling between chemical reactions and mechanical forces.

Fumio Motegi

PI

Hokkaido University

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Lab Website


A01-2
Mechano-chemical crosstalk regulating tissue patterning

This research aims at understanding the mechanisms by which spatially uniform cell aggregates acquire a functional pattern. Using inner cell mass in mammalian embryos as a model system, we will identify the mechanical force and its interaction with biochemical reactions, which enables cellular symmetry breaking and subsequent tissue patterning, and elucidate the principles of embryonic development.

Takashi Hiiragi

PI

Kyoto University

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Takafumi Ichikawa

Co-PI

Kyoto University

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A01-3
Epithelial self-organization by mechano-genomic crosstalk

This research aims to elucidate the mechanism of mechano-genomic crosstalk during embryonic development using Drosophila gastrulation as a model system. We will combine spatial transcriptomics with mechanical measurements and manipulation to investigate how fate and form emerge through mechanical self-organization.

Takefumi Kondo

PI

Kyoto University

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Yu-Chiun Wang

Co-PI

RIKEN BDR

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A02

Self-organization of multi-cellular systems by mechanical forces from extracellular spaces

Elucidate how “forces derived from the extracellular environment” control the emergence of tissue function.


A02-1
Mechanochemical feedback and emergence of tissue function in luminal tissues

We explore mechanochemical feedback in multiple luminal tissues during morphogenesis. We focus on the processes of the cells responding to the forces exerted by the lumen and transforming the luminal tissues. We will elucidate how the feedback mechanism between forces and molecules contributes to constructing organ morphology and its function.

Li-Kun Phng

PI

RIKEN BDR

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Toshihiko Fujimori

Asako Shindo

Co-PI

Kumamoto Universiy

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A02-2
Cooperation of mechanical forces during brain architecture formation

We will elucidate the mechanochemical coupling mechanism by which neurons and glia respond to external forces received from the environment while generating cell intrisic forces to produce the most effective movement and cell shape during the formation of the cellular architecture of the brain.

Mineko Kengaku

PI

Kyoto University

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Makoto Sato

Co-PI

Kanazawa University

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B01

Development of techniques for measurement, manipulation, and analysis of mechanical self-organization

Measure and manipulate forces applied to cell populations and the extracellular environment in living organisms, and quantitatively analyze their spatiotemporal patterns.


B01-1
Theoretical study of self-organization induced by mechanochemical feedback

This research aims to develop mathematical and computational methods for multi-scale and multi-dimensional analysis of mechanical actions and chemical reactions in living organisms to understand their “mechanical self-transformations”. Through our approaches, we will elucidate the principle that governs the autonomous control of living system by a mechanochemical feedback.

Tatsuo Shibata

PI

RIKEN BDR

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Satoru Okuda

Co-PI

Kanazawa University

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B01-2
Development of force-measuring techniques for biological tissues

This research aims to develop new techniques to measure and manipulate mechanical forces in cells and tissues by combining atomic force microscopy, magnetic tweezers, artificial cells, and optogenetic tools. These techniques will reveal mechanical forces exerted on intracellular spaces (e.g., the cell cortex and the cytoplasm) and extracellular spaces (e.g., extracellular matrix and inner cavity) in multi-cellular systems.

Shige H. Yoshimura

Shige H. Yoshimura

PI

Kyoto University

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Hirokazu Tanimoto

Hirokazu Tanimoto

Co-PI

Yokohama City University

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Makito Miyazaki

Makito Miyazaki

Co-PI

Kyoto University

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Call for Publicly Offered Research proposal

We are calling for projects that will conduct quantitative measurement and analysis of mechanical forces by incorporating and inventing new methods from physics and chemistry.

In addition, we expect research teams to investigate the physiological functions of mechanics by manipulating forces within cells and tissues while employing theoretical analyses.

We seek publicly-offered projects that will investigate a wide range of mechanical self-organization events.

The projects will be expected to not only complement and strengthen the planned research groups, but also to take up the challenge of establishing unique systems and innovative techniques to further accelerate the overall research aims.

Application Procedures forKAKENHI from JSPS

Announcement of Publicly Offered Research Online Briefing Session

For those who are intrested in applying publicly-offered projects in this research area, we will organize two briefing sessions via Zoom to explain our planned research projects and answer questions from the audience. Please make advance registration with below link.

First session: 2022. Sep. 9th(Fri) 16:00-17:00
Second session: 2022. Sep. 16th(Fri) 16:00-17:00
Zoom Info
Meeting ID: 699 308 5767
Passcode: FMYNSK


For inquiries

Transformative research areas (A): Mechanical self-transformation of living systems Administration Office
ADDRESS: Institute for Genetic Medicine, Hokkaido University Kita-15, Nishi-7, Kita-Ku, Sapporo, 060-0815, Japan
E-mail: multicellular_mechanics@igm.hokudai.ac.jp