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Prediction and control of cellular response by measuring the conformation of RAF

Research Project

Project/Area Number 24770161
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biophysics
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

HIBINO Kayo  独立行政法人理化学研究所, 生命システム研究センター, 研究員 (40435673)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords細胞内情報処理機構 / RAF / 細胞状態 / 細胞操作 / 細胞内1分子計測 / 1細胞計測 / FRET / 細胞動態計測 / ライブセルイメージング / 蛍光スペクトル計測 / 蛍光プローブ / 細胞内1分子解析 / 1分子FRET
Outline of Final Research Achievements

Uncontrollability of cell behaviors is a major obstacle to the therapeutic application of regenerative biology. To regulate cell behaviors, it is important to understand how cellular system works and to find the key factors to monitor and manipulate the cell-states.
Here, I focus on the signaling molecule RAS and RAF as a candidate factor to monitor and predict cell-states. RAS-RAF signaling involves proliferation, differentiation.
By using RAF-FRET probes, I found that the cellular response correlated with the ensemble RAF-conformation in individual cells before growth factor (GF)-stimulation and that the RAF-conformation depends on the phosphorylations. The results suggest that the phosphorylation state, therefore the ensemble RAF-conformation differs in individual cells and the difference induces varied responsibility to GF. The phosphorylation states of RAF could work as cellular memory which reflects the past extracellular environment and intracellular reactions.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (16 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (9 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Visualizing specific protein glycoforms by transmembrane fluorescence resonance energy transfer2012

    • Author(s)
      Haga, Y., Ishii, K., Hibino, K., Sako, Y., Ito, Y., Taniguchi, N., Suzuki, T
    • Journal Title

      Nature Communications

      Volume: 3 Issue: 1 Pages: 907-907

    • DOI

      10.1038/ncomms1906

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Live cell single-molecule detection in systems biology2011

    • Author(s)
      Sako, Y, Hiroshima, M., Pack, C.-G., Okamoto, K., Hibino, K., Yamamoto, A.
    • Journal Title

      WIREs Systems Biology and Medicine

      Volume: 4 Issue: 2 Pages: 183-192

    • DOI

      10.1002/wsbm.161

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Single-cell imaging analysis of conformation and function of disease-associated RAF mutants2015

    • Author(s)
      Hibino, K., Ueda, M., and Sako, Y.
    • Organizer
      第67回日本細胞生物学会大会
    • Place of Presentation
      タワーホール船堀(東京・江戸川区)
    • Year and Date
      2015-06-30 – 2015-07-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] Conformation and function of disease-associated RAF mutants2014

    • Author(s)
      Hibino, K., Ueda, M., and Sako, Y.
    • Organizer
      第52回日本生物物理学会年会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Polymorphism of a signaling protein RAF regulates cellular responses.2013

    • Author(s)
      Hibino, K., Okamoto, K., Ueda, M., and Sako, Y.
    • Organizer
      第51回日本生物物理学会年会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Single-molecule analysis of signaling protein RAF-conformation in living cells.2013

    • Author(s)
      Hibino, K., Okamoto, K., Ueda, M., and Sako, Y.
    • Organizer
      日本顕微鏡学会 第69回学術講演会
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
  • [Presentation] Signaling Molecule RAF: its conformation and cellular response2012

    • Author(s)
      日比野佳代
    • Organizer
      定量生物学の会第五回年会
    • Place of Presentation
      東京大学 駒場IIキャンパス 生産技術研究所(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] The conformation of signaling molecule RAF and the cellular response2012

    • Author(s)
      Hibino, K., Ueda, M., and Sako, M.
    • Organizer
      RIKEN Quantitative Biology Center Inaugural Symposium "Towards Whole-Cell Modeling"
    • Place of Presentation
      Kobe International Conference Center (Kobe)
    • Related Report
      2012 Research-status Report
  • [Presentation] 細胞内スペクトル計測を用いた情報伝達タンパク質RAFの構造とEGF応答の相関解析2012

    • Author(s)
      日比野佳代
    • Organizer
      理論と実験研究会
    • Place of Presentation
      広島大学理学部(西条)
    • Related Report
      2012 Research-status Report
  • [Presentation] Correlation between the molecular conformation and EGF response of RAF by FRET imaging in individual cells2012

    • Author(s)
      日比野佳代、上田昌宏、佐甲靖志
    • Organizer
      第50回日本生物物理学会年会
    • Place of Presentation
      名古屋大学(名古屋)
    • Related Report
      2012 Research-status Report
  • [Presentation] Correlation analysis of the molecular conformation and signal-responsiveness of RAF by FRET imaging in individual cells2012

    • Author(s)
      Hibino, K., Ueda, M., and Sako, M.
    • Organizer
      Joint Meeting of The 45th Annual Meeting of the Japanese Society of Developmental Biologists & The 64th Annual Meeting of the Japan Society for Cell Biology
    • Place of Presentation
      Kobe International Conference Center (Kobe)
    • Related Report
      2012 Research-status Report
  • [Book] 1分子FRET計測,「1分子生物学」2014

    • Author(s)
      日比野佳代
    • Total Pages
      9
    • Publisher
      化学同人
    • Related Report
      2014 Annual Research Report
  • [Book] 細胞内情報処理反応の1分子計測:タンパク質ダイナミクスと分子認識 「1分子ナノバイオ計測」2014

    • Author(s)
      佐甲靖志、廣島通夫、日比野佳代
    • Total Pages
      10
    • Publisher
      化学同人
    • Related Report
      2014 Annual Research Report
  • [Book] Single-Molecule Imaging Measurements of Protein-Protein Interactions in Living Cells.2013

    • Author(s)
      Hibino, K., Hiroshima, M., Nakamura Y., and Sako Y.
    • Total Pages
      22
    • Publisher
      InTech
    • Related Report
      2013 Research-status Report
  • [Remarks] QBIC Quantitative Biology Center, RIKEN

    • URL

      http://www.qbic.riken.jp/csd/ja/publication/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 理化学研究所 生命システム研究センター 細胞シグナル動態研究グループ

    • URL

      http://www.qbic.riken.jp/csd/ja/index.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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