2020 Fiscal Year Final Research Report
Spatiotemporal regulation of Inflammation and immune signals by ubiquitination and its mathematical simulation
| Project Area | Integrative understanding of biological signaling networks based on mathematical science |
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| Project/Area Number |
16H06575
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Complex systems
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
徳永 文稔 大阪市立大学, 大学院医学研究科, 教授 (00212069)
山本 瑞生 東京大学, 医科学研究所, 特任講師 (90750365)
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| Project Period (FY) |
2016-06-30 – 2021-03-31
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| Keywords | シグナル伝達 / 数理モデル / 炎症 / 免疫 / ユビキチン / 白血病 / 乳がん |
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| Outline of Final Research Achievements |
The function of the transcription factor NF-kB, which regulates gene expression, is tightly regulated in order to maintain human health. This regulation requires the coordinated action of multiple NF-kB activating proteins on a ubiquitin-linked scaffold. In this study, we succeeded in simulating the complex dynamics of the scaffold and activation proteins using mathematical science, considering time and intracellular space, and proposed a new mechanism of NF-kB regulation. In addition, we clarified new mechanisms of leukemia, neurological diseases, and malignant transformation of breast cancer caused by abnormal NF-kB activation.
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| Free Research Field |
細胞内シグナル伝達
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| Academic Significance and Societal Importance of the Research Achievements |
転写因子NF-kBの活性化は、その強さ、継続時間、周期性という点で、活性化を誘導する刺激や細胞によって異なり、その違いが誘導する標的遺伝子の種類を変化させることから、本研究の成果である活性化動態の数理シミュレーションはNF-kB活性化が誘導する多様な生命現象の理解に大きく貢献する。また、白血病や神経疾患の発症、乳がんの悪性化の原因となるNF-kB活性化異常の新たなメカニズムの解明は、治療薬の開発に繋がる重要な成果と考えられる。
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