Platform for Dynamic Approaches to Living System
from the MEXT, Japan

Molecular biology has shown successful progress in the last century in accordance with the establishment of molecular science that gave the comprehensive understanding of molecular structures and their associating chemical and physical properties. Well-established molecular science has allowed us to grasp the molecular details in the biological phenomena in atomic resolution. Particularly, in regard to the gene regulation as one of the most important biological processes, molecular biology has identified the various regulatory proteins in the genetic processes and showed how they cooperatively work to transcribe the gene codes inside the nucleus in cells; the genes or its carrier molecule DNAs are packed as a string of nucleosome particles, each of which comprises of DNA and histone proteins.

Molecular biology does not seem to be valid for describing the biological process in the higher-order molecular architecture, chromatin; chromatin is the ordered fiber comprising of nucleosomes. The technical development of the light microscope has revealed the dynamics of chromatin inside the nucleus. In addition, the genome-based approaches like chromatin conformation capture (3C) have shown the three-dimensional structure of chromatin based on the physical contact maps among the genes. The 3C and its relating approaches have also shown the dynamic structural rearrangement of chromatin according to the cellular state. In spite of the accumulated experimental data that have newly emerged, there is no appropriate theoretical frame to grasp the data together to establish to discuss the chromatin structures and dynamics with its associating functions. The chromatin is the higher-order molecular assembly. It, therefore, denies the understanding by the conventional and detailed molecular scientific views as applied to proteins and nucleosome analyses in atomic resolution. Rather, it may need the approaches using a coarse-grained polymer model; the polymer model has to represent the experimentally abstracted molecular features coming from the constituents of chromatin, which include nucleosomes, DNA, chemically modified DNA or histone proteins, and the associating proteins to nucleosomes in accordance to the cell events.

In this research project, we aim to establish the physical model of chromatin to describe various experimental observations of chromatin structural dynamics, which facilitate our understanding the biological phenomena occurring inside the cell nucleus. We are not sticking to specific cell biology phenomena, but are intriguing to seek for the unified chromatin physics to rationally explain various experimental observations.

The core research groups in this project are from the Department of Mathematical and Life Sciences, Graduate School of Sciences (MLS), Hiroshima University. The MLS has continuous efforts to prompt the interdisciplinary science over 10 years. In the past activities, we have set the original lecture courses to make the graduate students, coming from different departments, including mathematics, chemistry and biology, familiar with the interdisciplinary researches otherwise they will be never tough. In addition, we made inter-university contracts in the mathematics education with Meiji (Tokyo) and Ryukoku (Kyoto) Universities, which allow to exchange the graduate students among the universities. Our long-time activity in the interdisciplinary research is the basics for the RCMCD research.

In RCMCD, there are specially assigned researchers having different professions from physics to cell biology. They work together in the same laboratory space, in which they freely exchange their ideas and proceed with their collaboration works. In addition to the RCMCD researchers, the members from the MLS, Research Institute for Radiation Biology and Medicine (RIRBM), Graduate School of Advanced Sciences of Matter (ADSM), and Graduate School of Biomedical and Health Sciences (BHS) work together to achieve the project mission.