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- Spatiotemporal dynamics of intracellular components/
- [Cell Dynamics] Year Started : 2021
Professor
Graduate School of Frontier Biosciences
Osaka University
In eukaryotic chemotaxis, the intracellular self-organization of Ras and phosphatidylinositol lipids signaling system provides a mechanism to generate celularl polarity from the molecular noise. In this research project, we will quantitatively analyze the stochastic properties of the molecular components of the system by using single-molecule and super-resolution microscopy, and based on the measurement results, we will develop cellular simulations with single-molecule granularity to computationally reproduce the spatiotemporal dynamics of the signaling functions. In this way, we will elucidate the mechanism of the “fluctuation from micro to macro” or “organized randomness” of hierarchical molecular system in which the molecular noise is utilized to generate flexible environmental adaptation of living cells.
Project Professor
International Research Center for Neurointelligence (WPI-IRCN)
The University of Tokyo
Yoshiyuki Kubota | Associate Professor National Institute of Physiological Sciences National Institutes of Natural Sciences |
Yusuke Hirabayashi | Associate Professor Graduate School of Engineering The University of Tokyo |
Yoshiyuki Kubota | Senior Visiting Scientist Center for Brain Science RIKEN |
We investigate the origin of the mechanical coupling of brain spine synapses using optical microscopes (STED, confocal, 2-phtone) and electronmicroscopes (TEM and FIB-SEM). We will pay attention to the presynatpic synaptic vesicle clusters and to supra-molecular structure of SNARE proteins. In addition, we develop application for genetically encoded Au particle methods (AuNP) to elucidate the status of SNAREs in the vesicles and chemical manipulation of the pushing effects.
Professor
Exploratory Research Center on Life and Living Systems
National Institutes of Natural Sciences
Daisuke Koga | Associate Professor Department of Microscopic Anatomy and Cell Biology Asahikawa Medical University |
Takuro Tojima | Senior Research Scientist Center for Advanced Photonics RIKEN |
Totai Mitsuyama | Research Team Leader Artificial Intelligence Research Center National Institute of Advanced Industrial Science and Technology (AIST) |
The control of protein glycosylation is an important issue in the development of biopharmaceuticals. This study focuses on the Golgi apparatus as a stage for glycosylation and elucidates the spatio-temporal dynamics of its microstructure and the transport pathway of glycoproteins. By exploring the molecular mechanisms underlying the localization of glycosyltransferases and the selective transport of cargo molecules in the complexly compartmentalized Golgi, we aim to decipher the program of the secretory pathway and to control protein glycosylation by its modification.
Professor
Graduate School of Pharmaceutical Sciences
The University of Tokyo
Tomohiko Taguchi | Professor Graduate School of Life Sciences Tohoku University |
Kensuke Miyake | Professor Institute of Medical Science The University of Tokyo |
Nucleic acid sensing TLRs reside in the endosomal compartment and induce innate immune responses as pathogenic sensors. Recently, we found that these TLRs in macrophages sense lysosomal metabolite accumulation and activate stress responses such as macrophage proliferation. We here study mechanisms behind a decision by TLRs to activate innate immune responses or stress responses. We focus on: the structural studies of TLR complexes initiating immune responses or stress responses; and the relationship between these TLR complexes and spatiotemporal dynamics of lysosomes.
Professor
Graduate School of Pharmaceutical Sciences
Chiba University
Teppei Ikeya | Associate Professor Graduate School of Science Tokyo Metropolitan Univerity |
In this research project, we will develop (1) the methods for analyzing dynamic conformational equilibrium and ensemble structures of intracellular proteins, (2) the methods for extracting contribution of intracellular regulatory factors by in-cell NMR measurements using knockout cells, and (3) the techniques for subcellular localization of target proteins and their highly sensitive detection. We will apply these developed methods to higher-order structures such as LLPSs that are formed locally in cells, and quantitatively clarify the relationship between the dynamic structure and the functional role.
Professor
Graduate School of Frontier Biosciences
Osaka University
Masato T. Kanemaki | Professor National Institute of Genetics Research Organization of Information and Systems |
Toru Hirota | Division Head Cancer Institute Japanese Foundation for Cancer Research |
The kinetochore, which contains more than 100 proteins, is an essential structure for accurate chromosome segregation. Whereas various studies on the kinetochore are progressed, there remain many unsolved questions such as how the kinetochore structure is regulated in cells or how accurate chromosome segregation is performed through the kinetochore. In this project, using cryo-EM, high-resolution imaging, and genetic approach combined with cell biological methods, we will try to clarify how the structural changes of the kinetochore are related to the chromosome segregation process in cells.