Members

A03 : Theories on limited number of biomolecules in Biology, and Verification by in vitro Reconstruction

Experimental data obtained by Group A02 will be utilized in theoretical studies on Group A03. We plan to "carve out" reaction networks between limited biomolecules based on such dynamic data. The number of molecules required to support the assumption of "concentration" will be determined, and new concepts that may arise when considering molecular discreteness, will be discussed. Along with the analysis of the above experimental data, we will consider the traditional assumptions in reaction theories, e.g., the reaction rate constants are independent of the environment, the existence of well-defined reaction rate constants, and subsequently construct theoretical reaction models for the cell. Using these models, the biochemical systems can be reconstructed in silico, and with proper planning and design can be reconstructed in vitro, thus we can verify the validity and applicability of these models. Furthermore, as a model for the interaction among limited numbers of biomolecules, we will consider the bacterial flagellar proteins for the protein transporter systems with gene regulatory function. This can be reconstituted in artificial membranes, and analyzed to determine the "regulation of numbers" (proteins in the biomolecular complex) and serve as a feedback for the theoretical studies.

A03-1 : Constructing a theoretical framework to study the
reaction networks that involve a small number of molecules - development
of models by considering minority and hierarchy -

Name :

Togashi, Yuichi  HP

Affiliation :

Graduate School of Science, Hiroshima University

Major :

{Theoretical, Computational} Biophysics

Role :

Establishment of a theory for the reaction of minority molecules

Purpose

In the cell, various molecular species, present as a single molecule or as tens of thousands of molecules, affect one another in a hierarchical structure. When the "number" of biomolecules involved in such an interaction is limited (typically several to tens biomolecules), numerical discreteness (integerness) becomes significant, thus inducing instability in the feedback circuits. However, such molecular discreteness has the potential to confer plasticity and adaptability; hence, it plays an important role in biological systems. In this project, we will focus on these limited numbers of molecules and the structural hierarchy. Based on experimental data such as single-molecule measurements, we will focus on the high-order reaction networks to bridge the levels in hierarchy and determine the actual effects of the limited numbers and discreteness of biomolecules. A notable feature of biological systems is the combination of high "stability" (robustness) and moderate "instability" (plasticity and adaptability); our aim is to develop novel theories and general analytical techniques to quantitatively predict and verify the behavior and the mechanism that maintains this feature.

	Name	Affiliation	Major	Role
Co-Investigator (kenkyu-buntansha)
	Komatsuzaki, Tamiki HP	RIES, Hokkaido University	Nonlinear computational science	Developing a method to analyze the hierarchy of life
Co-Investigators (renkei kenkyusha)
	Li, Chun-Biu HP	RIES, Hokkaido University	Nonequibrium statistical physics	Support non-equilibrium statistical dynamics
	Teramoto, Osamu HP	RIES, Hokkaido University	Mathematical theory of chemistry	Support in the development of an appropriate theory about non-thermal insulation in the hierarchy of life
	Shinkai, Soya HP	Graduate School of Science, Hiroshima University	Nonequibrium statistical physics	Support the analysis of cellular dynamics
	Flechsig, Holger HP	Graduate School of Science, Hiroshima University	Theoretical biophysics	Support for the modeling of molecular machines

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A03-2 : Reconstitution of an in-vitro biological system driven and regulated by a small number of molecules

Name :

Imada, Katsumi  HP

Affiliation :

Graduate school of science, Osaka University

Major :

Structural Biology

Purpose

The bacterial flagellar protein secretion system is a large molecular assembly that is driven and regulated by the turnover of multifunctional component proteins, each of which functions in limited numbers. The flagellar gene expression is closely coupled with flagellar protein secretion, and the expression level is controlled by monitoring the types and numbers of molecules secreted. To understand the molecular mechanism underlying protein secretion, we will reconstitute in vitro secretion systems that will enable us to precisely control the environmental condition and monitor protein secretion. This study will reveal the effect of a limited number of biomolecules on flagellar biogenesis.

	Name	Affiliation	Major	Role
Co-Investigator (kenkyu-buntansha)
	Uchihashi, Takayuki HP	College of Science & Engineering, Kanazawa University	Engineering	Analysis of protein complex
Co-Investigators (renkei kenkyusha)
	Takeuchi, Shoji HP	Institute of Industrial Science, The University of Tokyo	Micro/Nano-devise
	Minamino, Tohru HP	Graduate school of Frontier Biosciences, Osaka University	Genetics	Development and analysis of protein engineering

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