Information

Genome modality

https://www.genome-modality.com

1. Details of Research Area

Since the discovery of DNA double helix, genome study has been expanded and our knowledge of the genome was enormously progressed. The past genome researches have forced on its informational aspects, such as replication, repair, recombination, and division of the genomic information and further highlighted epigenetic regulations to explain genetic phenomena. On the other hand, physical properties of the DNA, such as stiffness, torsion, supercoiling and so on, have been much less understood, although it is the most important properties directly affecting the genome structure. In this project, we will focus on physical properties of genome/DNA to understand how the genome builds its structure and how it functions. We define “genome modality” as a multi-dimensional mode to organize the structure and function of the genome. We will uncover bona fide figure of the genome from the perspective of genome modality. To this end, we utilize methods of biochemistry, cell biology, genome science, and polymer physics and create new field to study “genome modality.”

Objects of our research area are widely ranging from nanoscale DNA/nucleosome structures to organisms. Regulators of genome modality include nucleoplasmic/cytoplasmic environments, physical properties of proteins, and physicochemical reactions such as liquid-liquid phase separation, as well as physical properties of DNA. How do they regulate genome modality in each scale and define chromosome- or chromatin-dynamics, and how does dysfunction of the factors result in disorganization of cellular functions and causes diseases? We will address these questions from different approaches including theoretical physics, measurements of biophysical properties, reconstitutions, and genomics as well.

In the framework, there are 3 major categories as follows. A01: Physics of genome modality, where we uncover nanoscale genome structure and properties, and also build multi-scale theoretical model of the genome. A02: Mesoscale genome modality, where we focus on mesoscale structure including nucleosome, DNA loops, and chromatin fibers/domains, and figure out how these structures are formed. A03: Regulation of genome modality and disorders, where we address the questions how dysfunction of genome modality-regulating factors causes diseases.

2. Call for Proposals and Expectations for Publicly Offered Research, etc.

In publicly offered research, we invite experimental and theoretical studies uncovering genome structure in each scale, as well as studies developing multi-scale theory connecting A01 to A02 and A03. In A01, following studies are applicable; 1) Studies to understand nanoscale DNA physics, genome structure, and physics of the protein that regulates nanoscale DNA. 2) Studies to develop novel technologies to analyze DNA physics. 3) Studies to develop multi-scale theory for genome structure. These studies include, for instance, soft matter physics of DNA or genome, analyses for protein structure and intra-nuclear structure by using Cryo-EM or super resolution microscopy, modeling for chromatin/chromosome dynamics, theoretical or statistical analyses for Hi-C or chromatin dynamics. These studies dealing with nanoscale DNA physics are anticipated to develop into higher-order genome studies or cellular functions. In A02, studies to highlight mechanisms regulating mesoscale genome structure are applicable. For instance, these studies include analyses for DNA/chromatin loop formation, phase separation, physical properties of DNA/chromosomes/nucleus, single-molecule analyses of the proteins/DNAs regulating those mesoscale phenomena. In A03, genome structure studies in model/non-model organisms, studies uncovering relationship between genome structure and disorders, and studies to understand genome dynamics by using AI/machine learning are applicable.

In any of these research groups, we anticipate applications from young or female researchers. In the application form, “Theoretical research” or “Experimental research” should be declared.

3. Research Group, Upper Limit of Annual Budget and Number of research projects scheduled to be selected

https://www.mext.go.jp/a_menu/shinkou/hojyo/boshu/1394559_00004.htm

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