九州大学 大学院 システム生命科学府

Division of Medical Molecular Cell Biology

Contents

Division of Medical Molecular Cell Biology

In the post-genome era, the most important issue in human biology is the diversity at different levels of human nature such as “cell to cell”, “tissue to tissue”, “male and female” and “population to population”. The difference in disease susceptibility among individuals has been one of the critical issues in medical science. The mission of our division is to nurture researchers (and advanced technical experts) who can effectively address the issues in modern human biology. We expect young researchers not only to pursue the experiments intensively, but also to devise adequate experiments by fully utilizing the enormous ” omics ” data available.

In addition, current research in human biology must fully address bioethical issues based on the integration of perspectives from medical research and medical care, and the concerns of society and individuals. We provide comprehensive educational opportunities to students for the diverse field of medical genome sciences including molecular medicine, molecular biology, genetics and population genetics, structural biology, bioinformatics, and bioethics. We also provide the students the opportunities of joining in cutting-edge research projects, such as 1) the analysis of human variation viewed from genomic diversity; 2) the analysis of homeostatic mechanisms based on genome information; 3) the structural and functional analysis of proteins and their application for medicine; 4) the genetic analysis of multifactorial disorders and intractable disorders; and 5) the development of new methods of data analysis to expand the medical knowledge.

■Molecular Cell Biology

Professor Hisao Kondo

Department of Molecular Biology, Faculty of Medical Sciences (Hospital campus
E-mail:
URL:http://www.cellbiology.med.kyushu-u.ac.jp/saiboukougaku/Kondo-Lab.html

The Golgi apparatus is a center of membrane traffic and its biogenesis is one of the most important issues in cell biology. The Golgi apparatus undergoes the most dramatic transformation during the cell cycle. Once the eukaryotic cell enters the mitotic phase, it is fragmented and dispersed throughout the cytoplasm at mitosis. After cell division, the Golgi apparatus is rebuilt in each daughter cell from fragments. For its reassembly, at least two ATPases are necessary; N-ethylmaleimide-sensitive factor (NSF) and p97. Although the NSF pathway has been well characterized, the mechanism of the p97 pathway still remains unclear. We previously discovered two distinct p97ATPase-mediated membrane fusion machineries, the p97/p47 and p97/p37 pathways. In order to clarify the biogenesis of the ER and Golgi, we have been investigating the molecular mechanism of these two p97 membrane fusion pathways.

■Biology of Sex Differences

morohashi

Professor Ken-ichirou Morohashi

Department of Molecular Biology, Faculty of Medical Sciences (Hospital campus
E-mail:
URL:
Most organisms have developed the two sexes, male and female, and thus established sexual reproduction. The most prominent difference between the two sexes can be seen in the gonads, the testis in the male and the ovaries in the female. The gonads produce not only germ cells (sperm in the testis and eggs in the ovaries) but sex steroids (androgen in the male and estrogen in the female), which subsequently induce sex differences in throughout the whole body. Accordingly, sex differentiation of the gonads is the key event for establishment of sex differentiation of individuals. The early stages of the developing gonads are still sexually indifferent and thereafter sexually differentiated into the testis or ovary due to a combination of sex chromosomes. The aim of our study is to understand the mechanisms underlying sex differentiation of the gonads and whole body.

■Computational Biology

suyama_phot

Professor Mikita Suyama

Division of Bioinformatics, Medical Institute of Bioregulation
E-mail:
URL:http://www.bioreg.kyushu-u.ac.jp/labo/bioinfo/

The main focus of our group is in understanding the information written in genomes by computational biological approaches. More specifically, we are mainly analyzing genomic sequences and epigenomic data to get much insight into gene regulation. The current research topics include (1) comparative genome analyses and the analyses of the data from next generation sequencing platforms to understand the mechanisms of gene regulation, (2) molecular evolutionary analyses of gene duplications and genome rearrangements, and (3) gene expression by using data from RNA-seq and microarray.

■Medical Genomics

hi-shibata

Associate Professor Hiroki Shibata

Division of Genomics, Medical Institute of Bioregulation (Hospital campus
E-mail:
URL:http://www.gen.kyushu-u.ac.jp/~byouin/
What makes us human? The genetic and evolutionary bases of the highly sophisticated function of the human brain, such as cognition and intelligence are largely unknown. Psychiatric diseases are the natural model of dysfunction of the human brain. Therefore, genes that are susceptible to psychiatric diseases are strong candidates for genes involved in the evolutionary process of human brain function. To clarify the mode and the target of natural selection that has shaped human brain function, we are working on the following projects:

  1. comparative genomics of the glutamate receptor genes among primates.
  2. population genetics of the genes associated with major psychiatric diseases such as schizophrenia.

and

  1. genetic analysis of hereditary neurological diseases.

■Structural Life Science

kouda

Professor Daisuke Kohda

Division of Structural Biology, Medical Institute of Bioregulation (Hospital campus
E-mail:
URL:http://www.bioreg.kyushu-u.ac.jp/vsb/index.html
Structural biology is a powerful approach to understanding the functions of biomacromolecules on the basis of their structures at atomic resolutions. We focus on protein-protein and protein-peptide interactions under the concept of “structure at work”. We are particularly interested in molecular recognitions with non-strict specificity and weak affinity. We always carefully select targets, of which the structure will have an impact on their biological aspects. Our current targets include the mitochondrial protein import system, the N-glycosylation system, and the NADPH oxidase system. We use X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryoelectron microscopy. Although structure determination forms the core of our approach, it is essential that we also understand the tight coupling of structure determination and biology.

shimada2

Associate Professor Atsushi Shimada

Division of Structural Biology, Medical Institute of Bioregulation (Hospital campus
E-mail:
URL:http://www.bioreg.kyushu-u.ac.jp/vsb/index.html
Endocytosis and cell migration are dynamic processes of eukaryotic cells accompanied by membrane and/or actin cytoskeletal remodeling. These processes are regulated by cellular signaling pathways, which link extracellular signals to corresponding morphological changes of the cell. A number of proteins are involved in these pathways, including those with membrane and/or cytoskeletal remodeling activities. However, the detailed functions of these proteins at atomic resolutions are still not fully understood. To reveal the mechanisms underlying the functions exerted by these proteins, we use mainly X-ray crystallography and various biochemical techniques, such as isothermal titration calorimetry, for structural and functional analyses. We also perform cell biological analyses to test hypotheses derived from structural and functional analyses in collaboration with other groups.

■Integrated Omics

Kubota

Professor Hiroyuki Kubota

Research Center for Transomics Medicine, Medical Institute of Bioregulation (Hospital campus
E-mail:
URL:http://www.bioreg.kyushu-u.ac.jp/labo/omics/

Cell systems are regulated by a comprehensive network whichconsists of a huge number of molecules across multi-omics layers,such as genome, transcriptome, proteome and metabolome. Manydiseases are caused by malfunction of the network. Therefore,revealing the “Trans-Omics Network” not only leads to anunderstanding of diseases, but also applies to creating newmedicines. The primary aim of our laboratory is to developmethods of “Trans-Omics Analysis”, which integrates withmultiple omic layers to reconstruct trans-omics network forunderstanding the entire picture of the cell systems. The featuresof the identified trans-omics network will be revealed usingexperiments and computational analysis. Currently, we arefocusing on the insulin action, and trying to reveal the trans-omicsnetwork of the liver and muscle.

Uda

Associate Professor Shinsuke Uda

Division of Integrated Omics, Medical Institute of Bioregulation (Hospital campus
E-mail:
URL:http://www.bioreg.kyushu-u.ac.jp/labo/omics/
Measurement technology such as next generation sequencing
and mass spectrometry has been rapidly advanced, and allows
us to acquire omics data sets of each single layer: genome,
transcriptome, proteome, metabolome, and so on. Whereas
most of current research remain in single omics layer, since life
phenomena are caused in multi-omics layers, integration of
multi omics layers will become increasingly important. We are
working in collaboration with biologists, who acquire multi-omics
data sets. We develop analytical methods and apply those to the
multi-omics data sets by the framework of machine learning and
information theory.

■Cellular Memory

Tsukada

Professor Yuichi Tsukada

Advanced Biological Information Research Division,
INAMORI Frontier Reseach Center(Ito campus
E-mail:
URL:http://www.tsukada-lab.jp/
Multicellular organisms are consisted from a diverse range of
cell types. In the case of human being, the body is comprised of 60
trillion cells and the number of distinct cell types varies from 200
to 400. These various types of cells remember which types of the
cell they are, and function in accordance with their role in the body,
thereby homeostasis is maintained. However, if cells lose their
memory, they no longer are capable of functioning normally. As
a result, homeostasis is disrupted, leading to disease onset. The
diverse types of cells that compose an individual organism are all
derived from single totipotent cell, and share an identical genotype
(with some exceptions such as immune system cells). Despite
their identical genotype, the cells of the body have distinct cellular
phenotypes and functions that are attributable to the differences
between their gene-expression profiles. These gene-expression
profiles are established during development and maintained in
differentiated cells. For most of cell types in the body, programs
for gene expression become fixed once the cells differentiate and
maintained as cellular memory that defines cell identity. Given
that cellular memory is a fundamental mechanism that regulates
gene-expression program for multicellular organism, the goal of
our study is to elucidate the regulation mechanisms of cellular
memorys and artificial control of them.

■Metabolomics

Tsukada

Professor Takeshi Banba

Research Center for Transomics Medicine, Medical Institute of Bioregulation(Hospital campus
E-mail:
URL:http://bamba-lab.com/

Metabolomics, a field of research aimed at the comprehensiveanalysis of whole metabolites, is currently attracting substantialattention as an effective approach for high-resolution biochemicalphenotyping. This attention comes because metabolomics canbe used not only to identify simple metabolic variation butalso to detect almost imperceptible changes in the living body,which would be difficult to recognize as a common phenotypeby simultaneously expressing the relative proportions of multiplemetabolites. Our group works on the development of variousmetabolomics technologies (e.g., sample preparation, instrumentalanalysis, and data mining) and the application of metabolomicsresearch in a variety of fields, concentrating particularly on its usein medicine. Additionally, we energetically conduct transomics(also known as “multi-omics”) research, which involves integratedanalysis of data from metabolomics and other omics research,including genomics and proteomics.

Banba

Associate Professor Yoshihiro Izumi

Research Center for Transomics Medicine, Medical Institute of Bioregulation (Hospital campus
E-mail:
URL:http://bamba-lab.com/
With the recent breakthrough in metabolomics technologies,
application of metabolomics has been increasing in the medical
field. Identification and semiquantitation of the compounds in the
metabolome is defined as metabolic profiling, and it is applied
to define metabolic changes related to genetic differences,
environmental influences and disease or drug perturbations.
Medical metabolomics are two major purposes for its use; the
first is to acquire knowledge on the mechanisms of drug action or
the disease itself, and another is biomarker detection and disease
diagnosis. Our group has developed a novel high-sensitivity and
absolute quantitative metabolomics methodology based on gas
chromatography, liquid chromatography, and supercritical fluid
chromatography coupled to mass spectrometry. Advances in
metabolic profiling offer comprehensive coverage of a metabolome
as well as provide valuable insight towards understanding the
different biochemical profiles of a biosystem.

■Transcriptomics

Professor Yasuyuki Ookawa

Research Center for Transomics Medicine, Medical Institute of Bioregulation (Hospital campus
E-mail:
URL:http://tx.bioreg.kyushu-u.ac.jp/
My group has been interested in the mechanism to determine
cell fate in stem/progenitor cells. And we have approached to
understand it in chromatin structure at transcriptional regulation.
Our research has revealed new insights into the mechanisms of
genome-wide gene regulation by histone variants, nucleosome
positioning, and the overall organization of entire genomes inside
the nucleus in cell differentiation.
Graduate School of SystemsLife Sciences Kyushu University

Grad. Sch. Sys. Life Sci.
Kyushu University
744 Motooka
Nishi-ku 819-0395
Japan

Kyushu University
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