Laboratories

Laboratory of Systems Structural Biology Institute of Materials Structure Science,(High Energy Accelerator Research Organization;KEK) Recruiting students for the academic year 2018

Professor Toshiya SENDA
+81-29-879-6178
toshiya.senda{at}kek.jp
Lab HP

Associate Professor Ryuichi KATO
+81-29-879-6179
ryuichi.kato{at}kek.jp

Introduction

【Key Words】Synchrotron radiation, X-ray crystal structure analysis, Structual Biology

 The human body is composed of approximately 60 trillion cells,and although all somatic cells possess the same genetic information,they vary considerably in function with approximately 200 different cell types in humans. This diversity is considered to arise from different expression patterns of the genetic information. In eukaryotic cells,DNA molecules,of which the total length is approximately 2 meters in human cells,are accommodated in a small nucleus inside the cell. In the nucleus, DNA molecules make complexes with histone proteins, forming a compact structure called chromatin. However, this chromatin structure inhibits the interactions of molecular machines with DNA molecules, which are required for the reading of genetic information. The chromatin structure must therefore be disassembled in order for protein complexes to interact with DNA molecules and gene transcription to take place. Accordingly, eukaryotic cells have mechanisms that disassemble a specific region of the chromatin structure. Recent biological studies have revealed that chemical modifications on DNA and histone molecules function as biological information epigenetic information to regulate the expression pattern of genes. These chemical modifications appear to regulate the assembly and disassembly of the chromatin structure, thereby controlling the expression of genetic information. Importantly, these chemical modifications can be transferred from parent cells to daughter cells and maintain cell characteristics over cell generations
 To date, the transfer of chemical modifications on DNA have been intensively analyzed and the molecular mechanisms elucidated. Conversely,the molecular mechanisms of histone epigenetic information transfer remain elusive,mostly because the molecular system for the histone chemical modification transfer is quite complex:there are millions of histone molecules with different epigenetic marks in the nucleus and many proteins (protein complexes)are involved in the delivery of the histone molecules from the parent cell to the daughter cell. It is very difficult to solve this type of complex problem using only biochemical and biological means. The elucidation of molecular mechanisms of histone epigenetic information transfer is, however, of critical importance in the field of biology.
 Our group has tried to solve this problem using tertiary structure information of molecular complexes involved in the histone epigenetic information transfer. On the basis of tertiary structures of relevant complexes, we perform structure-based genetic and biochemical analyses to identify the function and mechanisms of the molecular complexes. We have so far proposed some models of the transfer of histone modifications and their functions (Nature, 446, 338-341 (2007),Proc. Natl. Acad. Sci. USA,107,8153-8158(2010), Proc. Natl. Acad. Sci. USA, 104, 4285-4290 (2007)).
 In order to determine the tertiary structure of protein complexes,we mainly use X-ray crystallography. Our laboratory is located in the KEK (high-energy accelerator research organization)and has regular access to the Photon Factory (PF), an X-ray source from synchrotron radiation. These beam lines for protein crystallography are quite powerful and have been utilized to determine many protein structures. Furthermore,we have a state-of-art wet laboratory for biochemistry and molecular biology.
 In addition to the above-described project, we have other research projects: 1) the molecular mechanism of cellular signal perturbation by a protein from Helicobacter pylori [Cell Host Microbe, 12, 20-33 (2012)], 2) structure-function mechanisms of enzymes with biological and industrial significance. We have also developed highly advanced X-ray beam lines for structural biology.
 We are looking to recruit highly motivated students who will be given the opportunity to work on cutting-edge research alongside experienced scientists. Students will have access to world-class facilities in a supportive environment.

Laboratories

The University of Tokyo
Graduate School of Frontier Sciences, The University of Tokyo

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