Research on regulatory mechanism for oscillation and switch-like response of NF-kB

• Project/Area Number: 15K21624
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Life / Health / Medical informatics; System genome science
• Research Institution: University of Miyazaki (2016-2017); Institute of Physical and Chemical Research (2015)
• Principal Investigator: Inoue Kentaro 宮崎大学, 工学部, 助教 (80708529)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: シグナル伝達 / 数理モデリング / シミュレーション / NF-kB / システム生物学 / モデリング

Outline of Final Research Achievements

Nuclear factor kappa B (NF-kB) is a transcription factor and is important for cell fate decision. The regulatory mechanism of NF-kB activation at molecular level is still unclear. We developed a mathematical model for NF-kB signal transduction system and focus on oscillatory behavior and switch-like response of NF-kB activity. Furthermore, we validated the results by biological experiments. The numerical and theoretical analysis showed that the mechanism of oscillatory behavior and switch-like response of NF-kB activity is not same but their behaviors can be interpolated by balance among amounts of molecules and reaction rates with respect to the activation. Our experiments supported the results.

Research Products

• [Journal Article] Oscillation Dynamics Underlies Functional Switching of NF-κB for B Cell Activation. (2016)
  • Author(s): Inoue K, Shinohara H, Behar M, Yumoto N, Tanaka G, Hoffmann A, Aihara K, Okada-Hatakeyama M.
  • Journal Title: npj Systems Biology and Applications Volume: 2 Issue: 1 Pages: 16024-16024
  • DOI: 10.1038/npjsba.2016.24
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Mathematical model and experiments for canonical NF-kB signaling (2018)
  • Author(s): Kentaro Inoue, Hisaaki Shinohara
  • Organizer: 新学術領域「数理シグナル」 第２回シンポジウム
• [Presentation] シグナル伝達系の数理モデル解析 (2017)
  • Author(s): 井上健太郎
  • Organizer: JSBi九州地域部会セミナー
  • Place of Presentation: 海峡メッセ下関(山口県・下関市)
  • Year and Date: 2017-03-10
• [Presentation] シグナル伝達系の大規模数理モデルにおけるパラメタ推定法 (2017)
  • Author(s): 井上健太郎
  • Organizer: 情報処理学会第51回バイオ情報学研究会
• [Presentation] シグナル伝達系における大規模モデルのシミュレーションに向けた研究 (2017)
  • Author(s): 井上健太郎
  • Organizer: ConBio2017
• [Presentation] Mathematical model for NF-κB signal transduction system (2016)
  • Author(s): Kentaro Inoue, Hisaaki Shinohara, Gouhei Tanaka, Kazuyuki Aihara, Mariko Okada-Hatakeyama
  • Organizer: The 2016 (26th) annual meeting of the Japanese Society for Mathematical Biology (JSMB2016)
  • Place of Presentation: 九州大学(福岡県・糸島市)
  • Year and Date: 2016-09-07
• [Presentation] Cooperative Mechanisms in Signaling Pathway for Switch-like Nuclear Translocation of NF-κB (2016)
  • Author(s): Kentaro Inoue, Hisaaki Shinohara, Kazunari Iwamoto, Michio Hiroshima, Yasushi Sako, Mariko Okada-Hatakeyama
  • Organizer: Single Molecule Approaches to Biology Gordon Research Conference
  • Place of Presentation: The Chinese University of Hong Kong (China)
  • Year and Date: 2016-07-03
  • Int'l Joint Research
• [Presentation] 実験と数理モデルによるNF-kappaBシグナル伝達システムの解析 (2016)
  • Author(s): 井上健太郎
  • Organizer: 第38回BMIRC研究会
  • Place of Presentation: 九州工業大学(福岡県・飯塚市)
  • Invited
• [Presentation] 定量的実験と数学モデルによるNF-kappaB活性化システムの統合解析 (2015)
  • Author(s): 井上健太郎, 篠原久明, 岡田眞里子
  • Organizer: 第38回分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド(兵庫県・神戸市)
  • Year and Date: 2015-12-01
• [Presentation] Dynamic modeling for oscillatory and switch-like behavior of NF-κB activity (2015)
  • Author(s): Kentaro Inoue, Hisaaki Shinohara, Mariko Okada-Hatakeyama
  • Organizer: International Conference of Systems Biology (ICSB2015)
  • Place of Presentation: BioPolis (Singapore)
  • Year and Date: 2015-11-23
  • Int'l Joint Research
• [Presentation] Dynamic model and experimental validation for oscillation and switch-like response of NF-κB activity (2015)
  • Author(s): Kentaro Inoue
  • Organizer: 生命医薬情報学連合大会2015
  • Place of Presentation: 京都大学宇治キャンパス(京都府・宇治市)
  • Year and Date: 2015-10-29
• [Remarks] Integrated Cellular Systems Lab.
  • URL: http://csb.rcai.riken.jp/?page_id=37