PURPOSE OF
THE RESEARCH PROJECT

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.

CONTENT OF
THE RESEARCH PROJECT

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.

Chromosome OS

chromosome OS
Open Recruitment
higher-order structure determination, systems biology, macromolecule modeling and simulation,
and physical property analysis of chromosomes and their environment.

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.

EXPECTED RESEARCH
ACHIEVEMENTS AND SCIENTIFIC SIGNIFICANCE

figure

2D & 3D
visualization on different scales:

structural mapping of annotated data

figure
  • Evaluate the relationship between 3D structure and disease phenotypes (e.g., quantitative assessment of chromosome plasticity)
  • Analyze the principles guiding the chromosome OS

Clustering and other analysesSample annotation (e.g., phenotype, chronological data)

  • Example:
    Global structure similarities

    Example:Global structure similarities

  • Example:
    Local structure similarities

    Example:Local structure similarities

  1. We will create the chromosome OS information platform in this project, a knowledge-basedsystematic annotation and visualization tool for documenting and explaining chromosomal behaviors in dynamic cellular processes (Figure2). This tool will help clarify the molecular basis for chromosomal integrity and will enhance our understanding of the pathogenesis of chromosome-linked diseases.
  2. We will also create a computer-based model that simulates multiple chromosomal functions. This model will have the potential for future application to a variety of fields including disease control and animal breeding.

Members and their research project
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
Technology
  3D-working principles of the device for DNA double strand break repair
05 Hiroyuki ARAKI National Institute
of Genetics
  Coordination of chromosome behavior based on the replication of chromosomal 3D structure
A01/02 06 Katsuhiko SHIRAHIGE Univ. Tokyo Genta NAGAE
Yuki OKADA
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
Technology
  Development of a computational algorithm for the prediction of chromosome tertiary structures based on NGS experimental data (=Chromosome OS platform)

Advisors

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.

Publication, News

Name Affiliation Specialized field
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
Basel, Switzerland
Cell biology
Camilla SJOGREN Karolinsla Institute, Sweden Cell biology

CONTACT INFORMATION

About science

Katsuhiko SHIRAHIGE
chros2015-at-gmail.com(please change “-at-” to @)

Reporting problems/requests of our website

Yuki OKADA
chros2015-at-gmail.com(please change “-at-” to @)

Requests of lectures and interviews

Yuri NAKAGAWA
chros2015-at-gmail.com(please change “-at-” to @)

Questions for each members’ projects, Please Directly contact to each member.