Research Theme
Analysis of the regulatory mechaisms of chromatin transcription through the structural analysis of TFIID
- Name
- Naruhiko Adachi
- Position, Research site
- Assistant Professor, Structural Biology Research Center (SBRC), Institute of Materials Structure Science (IMSS), High Energy Accelerator Research Organization (KEK)
General transcription initiation factor TFIID is a central factor for transcriptional activation from chromatin template. TFIID also plays a central role for sorting thousands of information reaching the inside and outside of the cell. In this project, we try to determine the tertiary structure of TFIID and TFIID containing-complex. Through the structural analyses, we try to elucidate the regulatory mechanisms of chromatin trasncription and sorting mechanisms of various information.
The protein structural diversity analysis by the advanced in-cell NMR technology
- Name
- Kohsuke Inomata
- Position, Research site
- Postdoctoral Researcher, RIKEN Quantitative Biology Center (QBiC)
The protein has the structural flexibility and diversity to exert biological functions efficiently. In this study, I try to elucidate "the protein structural diversity" inside living cells at the atomic level using the advanced in-cell NMR technology. Furthermore I will try to contribute to the drug discovery research by applying the in-cell NMR technology to drug target proteins.
Structural elucidation of the dynamical equilibria of GPCRs under lipid bilayer environment by NMR
- Name
- Takumi Ueda
- Position, Research site
- Assistant Professor, Graduate School of Pharmaceutical Sciences, the University of Tokyo
G-protein coupled receptors (GPCRs) are the receptors of various neurotransmitters and hormonis, and about 1/3 of the current drugs target GPCRs. In this study, I will clarify the mechianism of the activation and regulation of GPCRs by structural elucidation of the dynamical equilibria of GPCRs under lipid bilayer environment, by using NMR. This study would provide clues to develop drugs that have low side-effects with activating specific intracellular signaling pathways.
Elucidation of chemomechanical coupling mechanism of myosin V by advanced high-speed atomic force microscopy
- Name
- Noriyuki Kodera
- Position, Research site
- Associate Professor, Bio-AFM Frontier Research Center, Institute of Science & Engineering, Kanazawa University
High-speed atomic force microscopy (HS-AFM) allowed us to simultaneously observe “structure” and “dynamics” of functioning biological molecules in real time by rapidly palpating their surfaces with a cantilever probe-tip, In this research project, by enhancing this unique characteristic of HS-AFM, a new visualization technique that can apply a relatively strong force to only a target position on an object during HS-AFM imaging will be developed. The advanced imaging technique developed here will be applied to elucidate the chemomechanical coupling mechanism of myosin V, one of molecular motors.
Elucidation of working mechanisms of endoplasmic reticulum glycoprotein-folding machinery
- Name
- Tadashi Satoh
- Position, Research site
- Associate Professor, Graduate School of Pharmaceutical Sciences, Nagoya City University
The sugar chains operate as tags for quality control of glycoproteins, ensuring their appropriate folding and trafficking in cells. In this study, I focus on the glycoprotein-folding machinery serving as the bedrock of the quality control system in the endoplasmic reticulum. I aim to elucidate its working mechanisms using integrated structural biology approaches including X-ray crystallography, ultra-high field NMR spectrometry, and small-angle X-ray and neutron scattering assisted by deuterium labeling.
Innovative understanding of functional mechanism for supramolecular assembly of ion channels in lipid bilayer using atomic force microscopy
- Name
- Ayumi Sumino
- Position, Research site
- Assistant Professor, Institute for Frontier Science Initiative, Kanazawa University
Ion channels are essential membrane proteins that regulate the ion permeation through the cell membrane. Single-molecule studies have been extensively applied to functional analysis of the ion channel, but nobody knows whether the ion channel in actual cell membrane works as isolated single channel or not. In this study, I will develop simultaneous measurement system of ion channel structure and ionic current based on atomic force microscopy. The novel system will directly reveal the functional mechanism for supramolecular assembly of ion channels in lipid bilayer. The new insight will open up a new horizon for development of precisely-designed drugs.
Structural basis for gene expression regulation by Argonaute
- Name
- Kotaro Nakanishi
- Position, Research site
- Assistant Professor, Department of Chemistry & Biochemistry, Ohio State University
The goal of this project is to understand the mechanism of RNA interference that regulates gene expression by a ribonucleoprotein complex of Argonaute and small non-coding RNAs. To this end, we will use X-ray crystallography to determine the complex structures of Argonaute with different substrates at the atomic resolution. Our hypotheses derived from the determined structures will be thoroughly verified by biochemical and biophysical approaches. We believe this project will provide a solid foundation for all the researchers who study the RNA interference to develop their ideas and technologies toward clinical applications.
Development of new genome editing tools
- Name
- Hiroshi Nishimasu
- Position, Research site
- Assistant Professor, Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo
Engineered nucleases have received much attention as a genome editing tool. However, the mechanisms by which they specifically cleave target DNAs remain unclear. In this research, I aim to elucidate how engineered nucleases recognize and cleave the target DNAs, through structural and functional analyses. In addition, I aim to develop engineered nucleases that are able to cleave any DNA sequences.
Dynmics analysis of viral genome transcription machinery
- Name
- Takeshi Noda
- Position, Research site
- Professor, Institute for Frontier Life and Medical Sciences, Kyoto University
Transcription, the first step of the Central Dogma, is essential step for all of the organisms. Here, by using influenza virus vRNP as a model, which is viral genome transcription machnary of influenza virus, I analyse real-time dynamics of the genome transcription machinary during its transcription process from structural point of view. Such analyses will lead to further understanding of the transcription mechanism.
Correlative studies on autophagy proteins using 3D electron microscopy with precise spatial information
- Name
- Maho Hamasaki
- Position, Research site
- Associate Professor, Graduate school of Medicine, Osaka University
Many cellular functions are regulated by membrane dynamism that is controlled by proteins. Finding the link between the membrane dynamism and protein localization leads to solve the function of proteins. This study focuses on proteins involved in autophagy, which requires dynamic membrane events, using correlative light and electron microscopy combined with 3D electron tomography. The aim is to associate protein structures to their functions involved in membrane dynamism.
Investigation of structual dynamics of proteins using the relaxation mode analysis method
- Name
- Ayori Mitsutake
- Position, Research site
- Lecturer, Department of Physics, Faculty of Science and Technology, Keio University
Molecular dynamics simulations are a popular and powerful method for describing the motion of proteins in atomic detail. Because longer molecular dynamics simulations have been feasible in recent years, it is more important to develop a method to investigate dynamics of proteins. We develop new analysis methods to extract slow relaxation modes from complex motion of proteins and investigate the relationship between the slow modes and protein function. In the future, we will construct molecular dynamics simulation systems of molecular recognition by using our developed algorithms.
Novel platform to measure the membrane transport activity simultaneous with the conformational change of membrane proteins
- Name
- Rikiya Watanabe
- Position, Research site
- Assistant Professor, Graduate School of Engineering, The University of Tokyo
Membrane proteins carry out a wide range of physiological functions by regulating molecular transport across bio-membranes. We in this study develop the novel platform to measure the membrane transport activity simultaneous with the conformational change of membrane proteins, and attempt to directly elucidate the working principle of membrane proteins.