Control of B cell differentiation by manipulation of signal dynamics

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08534
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• 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)
• Research Collaborator: Inoue Kentarou ; Hoffman Alexander
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: B細胞シグナル / 反応速度数理モデル / 分子活性動態

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).

Free Research Field

システム免疫学