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