Chromosomes play a fundamental role
in many biological processes.Previous research efforts have advanced our understanding of specific chromosomal events,
such as DNA transcription,replication, recombination, partitioning, and epigenetic modification.
One of the major future challenges in chromosome biology will be to provide an overall framework
of how these individual activities are orchestrated and coordinated to maximize their effects
in a variety of biological processes that evolve over time.
In this project, we will elucidate the overarching coordinating mechanism
that enables a whole set of chromosomes to act as a single functional entity,
in both space and time, a new concept that we term “chromosome orchestration system (OS).”
For this purpose, we will investigate
(i) the mechanisms that determine three-dimensional (3D) chromosome architecture;
and (ii) the processes that integrate four-dimensional (4D, i.e., 3D plus time) information transmission.
New scientific knowledge gained from this project will further expand the horizon of drug discovery,
regenerative medicine, and other life sciences in Japan.
The main goal of this project is to describe the mechanisms
that regulate the functional unity of the chromosomes (chromosome OS)
by thoroughly examining the structural relationship between, and the hierarchy of,
individual chromosomal functions.
To this end, this project is composed of two groups of researchers, one focusing on the 3D structure and the other on 4D information processing (Figure 1).
In order to develop a complete understanding of the chromosomal plasticity and functional coordination, the 3D Group will combine molecular devices that mediate individual chromosomal functions and attempt to reconstitute large-scale 3D structures in vitro.
The 4D Group, on the other hand, will explore the dynamic, time-dependent processes for 3D chromosomal structure change during the cell cycle, meiosis, differentiation, stress response, and pathogenesis. The Group will further identify the decoding machinery that converts structural alterations into biologically relevant information.
While the activities of these two groups will be closely related and mutually complementary for the most part, there will be several topics that are addressed from different perspectives. As a common methodological basis, a chromosome OS information platform and a chromosome model will be developed.
|Category||#||Name||Affiliation||Collaborator||Title of the research project|
|A01||01||Tatsuya HIRANO||RIKEN||Miho OHSUGI||3D architecture of mitotic chromosomes|
|02||Tatsuo FUKAGAWA||Osaka Univ.||Chromosome architecture through centromeres|
|03||Akira SHINOHARA||Osaka Univ.||Regulation of chromosomal function during meiosis based on the 3D architecture|
|04||Hiroshi IWASAKI||Tokyo Institute of
|3D-working principles of the device for DNA double strand break repair|
|05||Hiroyuki ARAKI||National Institute
|Coordination of chromosome behavior based on the replication of chromosomal 3D structure|
|A01/02||06||Katsuhiko SHIRAHIGE||Univ. Tokyo||Genta NAGAE
|4D configuration of chromosome and cell differentiation|
|A02||07||Toru HIROTA||Cancer Institute||Kojiro ISHII||4D configuration of chromosome in acquiring chromosome instability|
|08||Yumiko IMAI||Akita Univ.||4D configuration of host chromosome as a response against viral infection|
|09||Takehiko ITOH||Tokyo Institute of
|Development of a computational algorithm for the prediction of chromosome tertiary structures based on NGS experimental data (=Chromosome OS platform)|
Seven extraordinary researchers of
chromosome/genetic field, 3 from Japan and 4 from oversea countries, are designated as advisors of our project.
To take advantage of this opportunity,
international symposiums held at oversea countries are planned to actively exchange the information and techniques with the advisors.
|Tetsuji KAKUTANI||National Institute of Genetics, Japan||Molecular genetics|
|Haruhiko KOSEKI||RIKEN, Japan||Molecular biology|
|Haruhiko SHIOMI||Keio Univ., Japan||Molecular biology|
|John DIFFLEY||National Cancer Institute, UK||Molecular genetics|
|Frank UHLMANN||Oxford Univ. UK||Molecular biology|
|Susan GASSER||Friedrich Miescher Institute, University of
|Camilla SJOGREN||Karolinsla Institute, Sweden||Cell biology|
Questions for each members’ projects, Please Directly contact to each member.