| Project/Area Number |
15K08534
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
SHINOHARA HISAAKI 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 上級研究員 (10391971)
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| Research Collaborator |
Inoue Kentarou
Hoffman Alexander
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | B細胞シグナル / 反応速度数理モデル / 分子活性動態 / シグナル活性動態 / B細胞 / 細胞分化 / シグナルネットワーク / シグナル動態 / 数理モデル解析 / 遺伝子発現解析 / シグナル動態制御 / 分化決定システム |
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| Outline of Final Research Achievements |
In the BCR signal, the elements necessary for activation of NF-κB were indeterminate. The applicant investigated physiologically and clarified that TAK1 is essential for B cell activation and cell differentiation (Immunol Cell Biol. 2016, Genes Cells. 2016). In addition, molecular based analysis showed that TAK1-associated molecule TAB 2/3 is essential for activation of NF-κB (FEBS Lett. 2016).
Applicant quantitatively measured cell input / output and using mathematical model analysis, revealed that IKK's steep activity kinetics are controlled by "positive Feedback mechanism" (NPJ Syst Biol. 2016). In parallel with these, I find a ubiquitinating enzyme IAP controls the activity dynamics of ERK and IKK using gene expression analysis and reaction rate mathematical model (Sci Rep. 2016). Furthermore, it is clarified that epigenetic control by BCR stimulation is also mediated by NF-κB (submitting).
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