Structural Life Science and Advanced Core Technologies for Innovative Life Science Research

Strategic Objective

Creation of new technologies for breakthrough in understanding and predicting biological activities and intermolecular interactions by means of “Novel Structural Life Science” that contributes to new medical treatment and prevention of various diseases, food safety enhancement and environmental improvement

Research Supervisor


Keiji Tanaka (Director, Tokyo Metropolitan Institute of Medical Science)

Outline

This Research Area aims to integrate cutting-edge life science areas with structural biology for creating “structural life science” and advanced core technologies that will lead to innovation in life science. It will address fundamental problems in life science by integrating advanced methods of structural analysis seamlessly and establishing general principles for elucidating and predicting dynamics of hierarchical structures ranging from the atomic to the cellular and/or tissue levels.
The recent large-scale research projects in structural biology in Japan have achieved major advances in determination of protein structures with biological significance. Proteins play key roles in biological events; however, they do not function alone. Therefore, the next important step is to determine the dynamics of such proteins and to study the functional mechanisms underlying the interactions among proteins and various other biological macromolecules. For example, many diseases of animals and plants are caused by protein abnormalities. Thus, structural life science, a new branch of science proposed for understanding biological phenomena of fundamental importance based on structural methods, should play an essential role in elucidating molecular mechanisms and developing new therapeutic methods and means of disease prevention. The structural life science approach is also required for promoting a healthy and long-lived society, establishing safe food production systems, and solving environmental problems. Structural life science addresses these issues by establishing general principles underlying temporal and spatial changes of biological systems at the atomic or molecular level and by predicting dynamics of biological phenomena from these principles.
Utilizing the structural life science approaches, this CREST Research Area seeks to analyze dynamics of important functional machineries involved in biological phenomena, for example, large protein complexes and organelles; to identify pathogens and determine their structures in complex with cognate interaction molecules; to search efficiently lead compounds for structure-based drug discovery processes; and to create advanced technologies required for such studies.

Topics

・2015.07.07 JST CREST-PRESTO joint international symposium ~Structural Biological Dynamics: From Molecules to Life with 60 trillion Cells~ will be held on November 5-6, 2015.
We look forward to meeting you at the symposium in Tokyo. Conglaturations!
バナー

Research Supervisor’s Policy on Call for Application, Selection, and Management of the Research Area (FY2014)

One of the key life science themes to be tackled under this program is driven by the new field of “structural life sciences”, which combines next-generation structural biology developed based on the traditions and scientific capabilities of structural biology cultivated thus far in Japan with wide-ranging bioscience research. The goal of structural life science is to further our understanding of protein structures and to use these structures to achieve dramatic advances in research for the benefit of society.
The policies and basic focus for the 2014 research proposal submissions are similar to those in previous years, but as this year is the final year for research proposal submissions in this field, we particularly welcome proposals in fields where few selections have been made to date. For example, we welcome proposals on food additives and how they relate to food safety; research that may lead to the development of new testing, preventive, or treatment methods for bacteria/viruses that case food poisoning; or research that may result in the cultivation of plants relevant to environment issues. As before, we expect structural research to include programs to contribute to the further development of life science research, including more advanced research methods (e.g., for crystal structure analysis, solution scattering, nuclear magnetic resonance, electron microscopy, single-molecule observations, molecular imaging, single-particle analysis of protein composites, mass spectrometry, computational science, bioinformatics, and analytical methods for various types of interactions), new multidimensional research methods, and completely novel techniques. Structural research should not focus exclusively on proteins, but may also include conjugates or complexes of proteins with nucleic acids, lipids, or sugars. The key focus is research into the structure and function of biomacromolecules to better understand the molecular basis for life in both prokaryotes and eukaryotes and to apply this knowledge. The objective of structural research is to clarify the molecular recognition mechanisms that allow spatiotemporal changes in proteins, which in turn are produced by biomolecular interactions and modifications or by small-molecule compounds. We also welcome research into the use of structures that will contribute to development in the healthcare, agriculture, and biotechnology industries.
It is not a requirement that the Research Director be specialized in structural biology, but consideration should be given to participation by structural biologists within the research team. In terms of the size of research team, we are targeting total research spending of ¥200?300 million. Explanations should be provided if the scale of the research project differs significantly from this guideline. During the screening process, we may ask external specialists to review the documents to provide a fair assessment if our Research Area Advisors are unable to provide a thorough evaluation of the R&D field in the proposal.
In terms of management of research within particular fields, systems will be put into place to support additive and synergistic outcomes through opportunities for information exchange and joint research, emphasizing links within the CREST research field as well as the PRESTO research field with the same Strategic Object (Structural life science and advanced core technologies for innovative life science research) and the Platform for Drug Discovery, Informatics, and Structural Life Science at the Ministry of Education, Culture, Sports, Science and Technology (MEXT).

This CREST Research Area emphasizes collaboration not only across CREST grant recipients, but also with participants in the Precursory Research for Embryonic Science and Technology “Structural Life Science” and the Ministry of Education, Culture, Sports, Science and Technology “Platform for Drug Design, Discovery and Development” projects, which were launched at the same time. Accordingly, we will foster a broad coordination and cooperation with other related projects by providing frequent opportunities for cross-fertilization of ideas relating to life science research and structural biology. We hope that this will lead to new ideas and collaborative research.

Research Area Advisors

・Yoshinori OHSUMI, Ph.D.
The Title of Honorary Professor, Tokyo Institute of Technology

・ Takashi GOJOBORI, Ph.D.
Vice-Director, National Institute of Genetics

・Ichio SHIMADA, Ph.D.
Professor, University of Tokyo

・Motowo NAKAJIMA, Ph.D.
Director & CSO SBI Pharmaceuticals Co.Ltd.

・Toshio HAKOSHIMA, Ph.D.
Professor, Nara Institute of Science and Technology

・Yoshinori FUJIYOSHI, Ph.D.
Professor, Nagoya University

・Toshio FURUYA, Ph.D.
President & CEO PharmaDesign,Inc.

・Masayuki MIURA, Ph.D.
Professor, University of Tokyo

・Yuriko YAMAGATA, Ph.D.
Professor, Kumamoto University

・Masasuke YOSHIDA, Ph.D.
Senior Research Fellow, Kyoto Sangyo University

Year Started : 2012

Elucidation of the structural and functional network with mitochondria as a hub

Research Director:
Toshiya Endo (Professor,Department of Molecular Biosciences、Kyoto Sangyo University)

Structural biology of infection and carcinogenesis by Helicobacter Pylori

Research Director:
Toshiya Senda(Professor, High Energy Accelerator Research Organization “KEK”)

Structural studies of the mitochondrial respiratory chain – structure impacts efficiency-.

Research Director:
Tomitake Tsukihara (Professor, University of Hyogo)

Structural basis of biological system for energy metabolism using dihydrogen

Research Director:
Yoshiki Higuchi(Professor, University of Hyogo)

Structural life science of membrane receptor complexes and their downstream signaling for synapse formation.

Research Director:
Shuya Fukai(Associate Professor, The University of Tokyo)

Studies on the structural basis of multidrug efflux transport and the development of multidrug transporter inhibitors.

Research Director:
Akihito Yamaguchi(Professor, Osaka University)

Year Started : 2013

Dynamic structural lifescience of protein machinery driven by ATP/GTP

Research Director:
Toshio Ando(Professor, Kanazawa University)

Molecular studies of RNA-dysmetabolic syndrome – From ribonucleoproteomics to structural life science –

Research Director:
Toshiaki ISOBE(Professor, Tokyo Metropolitan University)

Establishment of in situ structural biology through the integration of NMR and computational science and its application to the investigation of eukaryotic intracellular protein behaviours

Research Director:
Yutaka Ito(Professor, Tokyo Metropolitan University)

Structural Studies on the transient macromolecular complexes formed upon photoacclimation

Research Director:
Genji, Kurisu(Professor, Osaka University)

Structural analyses of Toll-like receptors sensing single stranded nucleic acids in innate immunity and their application

Research Director:
Toshiyuki Shimizu(Professor, The University of Tokyo)

Maintenace of ER homeostasis: Crosstalks of redox regulation with calcium regulatiojn and protein quality control in the ER.

Research Director:
Kazuhiro Nagata(Professor, Kyoto Sangyo University)

Structural life science for unveiling membrane dynamics during autophagy

Research Director:
Nobuo N. Noda(Chief Researcher, Microbial Chemistry Research Foundation)

Year Started : 2014

Cellular structural biology of cilia/flagella

Research Director:
Masahide Kikkawa(Professor, Graduate School of Medicine, The University of Tokyo)

Structural and Functional Analysis of Mitochondrial Oxidative Phosphorylation to Develop the New Therapeutic Method

Research Director:
Seiji Takashima(Professor, Graduate School of Medicine, Osaka University)

Structural studies of the proteins working in novel cell membrane potential signal

Research Director:
Atsushi Nakagawa(Professor, Institute for Protein Research, Osaka University)

Asymmetrical distribution of phospholipids at plasma membranes, and its breakdown

Research Director:
Shigekazu Nagata(Specially Appointed Professor, Immunology Frontire Research Center,Osaka University)

Molecular mechanisms of gravitropic signaling in the sensing cells〜From molecular structure to plant organ response〜

Research Director:
Miyo T. Morita(Professor, Graduate School of Bioagricultural Sciences, Nagoya University)

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