Cell Innovation


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Introduction

Life science aims to investigate and elucidate the often complex and exquisite mechanisms underlying biological phenomena. Advancing life science research in areas such as new drug development, increased food production, and creation of new industries is key to reinforcing the industrial competitiveness of Japan.

The complete set of an organism's genes is referred to as its genome, and this information is retained in the form of DNA molecules contained in the cellular nucleus and other organelles. The human genome is comprised of approximately three billion base pairs, for which the entire sequence was completed in 2003 by the international Human Genome Project.

With the completion of the human genome sequence, the Ministry of Education, Culture, Sports, Science and Technology conducted the Genome Network Project from FY2004 to FY2008. Intracellularly, proteins are produced based on the nucleotide (a unit of DNA) sequences of genes contained in the genome, and function in complex interactions with other genes and proteins. The Genome Network Project investigated the networks of human genes and proteins to consolidate the results as a database, studied biological phenomena including development and immunity, and conducted basic biomedical research of diseases such as cancer and diabetes.

In addition, the Cell Innovation Program, begun in FY2009, is intended to make the best use of the results, equipment, human resources, and data obtained from the Genome Network Project. This program will conduct an unprecedented large-scale, multidisciplinary analysis of genome-based information using next-generation sequencers with innovative data production performance in combination with intracellular imaging technology to further understanding of the mechanisms of biological phenomena at the cellular level.

Significance and Background of the Program

Currently, Europe, the US, and Asian countries are aggressively promoting national projects to investigate genomic sequences and functions, the foundation for life science studies. In Japan, advancing life science research entails placing full emphasis on research aimed at understanding cellular functional systems, such as gene expression regulation, signal transduction, and metabolic regulation.

  • There has been remarkable progress in development of sequencing technology used in genome-based information analysis. Ultra-high-speed, next-generation sequencers that provide performance far superior to conventional sequencers have already been applied. Sequencing centers already operate in the US, UK, China, and Singapore; thus, to maintain the international competitiveness in life science research, there is an urgent need for a sequencing center in Japan. Additionally, a data analysis center is needed to handle the vast amount of diverse data produced by next-generation sequencers.
  • In order to analyze and understand temporal biological phenomena at the cellular level, such as development/ differentiation and cancer formation, cellular information must be continuously monitored over time. Genome-based information, which serves as a comprehensive snapshot of cellular information at a particular point in time, must be analyzed simultaneously.

Expected Effects

The analysis of cellular programs will provide basic findings and technology necessary for understanding the mechanisms of various disorders and diseases, and for developing therapies, including new preventive and diagnostic methods and pharmaceutical agents. Additionally, the platform facilities constructed through the Program, including the Sequencing Center, will be open for public use by life science researchers in universities and business organizations. The Program will promote the use of such a platform in a wide range of research fields.

Program Structure

  • Sequencing Center
    DNA sequencers were used in the sequencing of the human genome. These instruments automatically read the nucleotide sequence of chromosomal and cytosolic DNA (the genome). These sequencers enabled sequencing at speeds 100- to 1000-fold faster than manual sequencing. In recent years, next-generation sequencers have been developed that increase sequencing speed by another 100- to 1000-fold. This innovative technological development has made it possible to obtain not only the nucleotide sequences of genomic DNA, but also genome-based information such as the transcriptome, the type and amount of RNA (a mediator between genes and traits) present, and the epigenome, the changes in genomic structure that influence the effects of genes. Thus, in order to systematically collect sequence information on a large scale, a Sequencing Center equipped with a number of next-generation sequencers will be established. The Sequencing Center will produce various data, develop technologies that can ensure the accuracy of sequence information produced by next-generation sequencers, and analyze the location of sequences on the genome and putative functions encoded by those sequences in cooperation with the Data Analysis Center (primary analysis).
  • Data Analysis Center
    This program will establish a Data Analysis Center equipped with computer resources sufficient to handle the vast amount of data produced by the Sequencing Center. In cooperation with the Leading Research Projects, the Data Analysis Center will analyze primary Sequencing Center data to help understand the biological significance and association between the various data generated (secondary analysis).

    Primary and secondary analysis data, along with other data produced by the Leading Research Projects, will be compiled into databases, integrating existing data, including results from the Genome Network Project, to construct a platform for understanding complex intracellular biological phenomena.
  • Leading Research Projects
    Research projects linking data from the application of next-generation sequencers to cellular function analysis are classified into two categories: Project A and Project B.

    Studies in Project A utilize various data obtained through the next-generation sequencers at the Sequencing Center to analyze transcriptome behavior and structural changes in genes and chromosomes in target cells of interest. Simultaneous studies focus on development of imaging technology to visualize cellular status using biomarkers such as GFP (green fluorescent protein), as well as studies in systems biology whose aim is to understand the cell as a system, in order to clarify cellular function. Studies in Project B seek to develop innovative next-generation sequencer technology to acquire cellular function information that cannot be obtained using conventional technologies, and then, investigate cellular functions using the acquired information.

Research Promotion Organization

A program director(PD) and program officers(POs) have been appointed to ensure the smooth operation of the Cell Innovation Program. In addition, the following have also been set up to support the Program: a Steering committee to plan and discuss the year-round schedule, to comprehend the progress and to discuss the other issues; an Excective committee to exchange views between representative researchers; and an Ethical working group(WG) to discuss ethical issues, such as proper handling of personal genomic information.

Moreover, an administrative office has been set up to support the smooth promotion of the whole program via information sharing between the two centers and each Leading Research Project, operations of the Steering committee and WG, and public relations, in collaboration with the PD, POs, and investigators.

Data Analysis Center

Principal investigator Representative institution Research project Remarks
Kazuho Ikeo National Institute of Genetics, Research Organization of Information and Systems Establishment of the Data Analysis Center and Information Research & Development
Co-operative research project's
Co-investigator Co-operative institution Sub-theme Remarks
Tetsuro Toyoda RIKEN Bioinformatics and Systems Engineering Division Development of Highly Accurate Sensing Technology by Omics Integration Analysis,and Application to Construction of an Annotation DB for Image Analysis
Shinichi Morishita Institute of Medical Science, The University of Tokyo Technological Development for in silico Cellular System Analysis
Akira Mihara Institute of Medical Science, The University of Tokyo Trend Survey and Research Promotion in Cell Innovation

Sequencing Center

Principal investigator Representative institution Research project Remarks
Yasuyoshi Watanabe RIKEN Center for Life Science Technologies Establishment and Operation of the Next-Generation Sequencer Center

Leading Research: Project A

Principal investigator Representative institution Research project Remarks
Michiyuki Matsuda Graduate School of Biostudies, Kyoto University Integrated Systems Analysis of Cellular Oncogenic Signaling Networks
Co-operative research project's
Co-investigator Co-operative institution Sub-theme Remarks
Tetsu Akiyama Institute of Molecular and Cellular Biosciences, The University of Tokyo Systems Analysis of Cellular Oncogenic Signals Based on Gene Expression Analysis: Understanding the System Regulating Cancer Cell Proliferation and Invasion by Time-Series Phosphorylation Proteomics
Mariko Okada RIKEN Research Center for Allergy and Immunology Informatics Analysis of Signal Transcription Networks
Principal investigator Representative institution Research project Remarks
Satoshi Inoue Graduate School of Medicine, The University of Tokyo Elucidation of Regulatory Systems for Prostate and Breast Cancer Cells Utilizing Next-Generation Sequencing
Co-operative research project's
Co-investigator Co-operative institution Sub-theme Remarks
Kuniko Horie Research Center for Genomic Medicine, Saitama Medical University Preparation of Hormone Therapy-Resistant Cancer Cells and Expression Function Analysis of Hormone Receptor Target Factors in Clinical Breast Cancer Samples
Hiroyuki Mano Division of Functional Genomics, Jichi Medical University Exhaustive Analysis of microRNA Expression Profiles in Breast Cancer Cells
Shigeru Kondo Graduate School of Frontier Biosciences, Osaka University Systems Biology Analysis of the Mechanisms Underlying Acquired Hormone Therapy Resistance in Cancer Cells FY2009-FY2011
Ryuichi Sakai Growth Factor Division, National Cancer Center Research Institute Imaging Analysis of Metastasis Signaling in Prostate and Breast Cancers FY2009-FY2011
Principal investigator Representative institution Research project Remarks
Hiroki Ueda RIKEN Center for Developmental Biology Understanding the Cell Ratio Regulation Network and Cellular Hebbian Learning Rule
Principal investigator Representative institution Research project Remarks
Katsuhiko Shirahige Institute of Molecular and Cellular Biosciences, The University of Tokyo Innovative Research on the Choreography of Male and Female Chromosomes in Early Development
Co-operative research project's
Co-investigator Co-operative institution Sub-theme Remarks
Takeo Kishimoto Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology Research on the Choreography of Male and Female Chromosomes Using Live Imaging and Cell Biological Approach
Principal investigator Representative institution Research project Remarks
Yasushi Okazaki Research Center for Genomic Medicine,Saitama Medical University Systematic Search for Mutations in Mitochondrial Respiratory Chain Disorder and Functional Analysis Focusing on Neural Cells a new accepted project in 2010
Principal investigator Representative institution Research project Remarks
Masatoshi Hagiwara Graduate School of Medicine, Kyoto University Decipherment of Splicing Code and Search for Therapeutic Approaches to RNA Diseases Based on Extensive Analysis of the Transcriptome a new accepted project in 2010
Co-operative research project's window open
Co-investigator Co-operative institution Sub-theme Remarks
Takamitsu Hosoya Graduate School of Biomedical Science, Tokyo Medical and Dental University Development of Splicing Modulator Compounds a new accepted project in 2010
Kinji Ohno Graduate School of Medicine, Nagoya University Exhaustive Analysis of Splicing Regulatory Sequence Using Exon-Specific Array/CLIP a new accepted project in 2010

Leading Research: Project B

Principal investigator Representative institution Research project Remarks
Atsushi Miyawaki RIKEN Brain Science Institute Development of Optical Sampling Technology for Sequencing Analysis of Individual Cells
Principal investigator Representative institution Research project Remarks
Takashi Ito Graduate School of Science, The University of Tokyo Development of High-Performance Epigenome Sequencing Technologies for Innovative Cell Biologyy
Co-operative research project's
Co-investigator Co-operative institution Sub-theme Remarks
Kinichi Nakashima Graduate School of Biological Sciences, Nara Institute of Science and Technology Exhaustive Epigenome Analysis in Relation to Neural Stem Cell Differentiation and Flexibility FY2009-FY2011
Principal investigator Representative institution Research project Remarks
Hideki Kambara Central Research Laboratory, Hitachi, Ltd. Development of Pretreatment Technology for Exhaustive Analysis of mRNA in a Single Cell a new accepted project in 2010
Principal investigator Representative institution Research project Remarks
Yumiko Saga Genetic Strains Research Center, National Institute of Genetics, Research Organization of Information and Systems Mechanisms Involved in the Development and Differentiation of Germ Cells, Including Spermatogenic Stem Cells FY2009-FY2011