2020 Fiscal Year Final Research Report

Elucidation of MAPK signaling pathways and biological processes based on mathematical science

Planned Research

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Project Area	Integrative understanding of biological signaling networks based on mathematical science
Project/Area Number	16H06574
Research Category	Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Allocation Type	Single-year Grants
Review Section	Complex systems
Research Institution	The University of Tokyo
Principal Investigator	Takekawa Mutsuhiro 東京大学, 医科学研究所, 教授 (30322332)
Co-Investigator(Kenkyū-buntansha)	上野匡東京大学, 大学院薬学系研究科(薬学部), 助教 (60462660) 石谷隆一郎東京大学, 大学院理学系研究科(理学部), 特任教授 (90361568)
Project Period (FY)	2016-06-30 – 2021-03-31
Keywords	シグナル伝達 / MAPキナーゼ / 情報科学 / 数理解析 / がん / ストレス応答
Outline of Final Research Achievements	In mammalian cells, a wide array of extracellular stimuli generates intracellular signals that converge on a limited number of protein kinase cascades, commonly referred to as MAPK pathways. In mammals, there are at least three subfamilies of MAPKs, named p38, JNK, and ERK. While the classical ERK MAPK is mainly activated by mitogenic stimuli, two relatively newly identified MAPKs, p38 and JNK, are preferentially activated by various environmental stresses. Perturbation of these critical signaling systems is involved in a variety of life-threatening diseases, including cancers and autoimmune diseases. In this study, we investigated the regulatory mechanisms and roles of these signaling pathways in cell fate decisions by combining experimental approaches using molecular biology and multi-omics techniques with theoretical approaches based on mathematical science. We also analyzed abnormalities of these signaling pathways in human diseases including cancer and inflammation.
Free Research Field	分子病態医科学
Academic Significance and Societal Importance of the Research Achievements	シグナル伝達分子のオミクス解析により、新規MAPK基質分子やMAPK依存的発現誘導遺伝子を複数同定することに成功すると共に、MAPK経路の新たな制御機構が明らかとなった。また、情報科学やバイオインフォマティクスの手法を用いて、オミクス解析データから生命機能制の鍵となる分子を抽出することに成功した。さらに、分子イメージング解析によってシグナル伝達分子の時空間変動を捉えることにも成功し、数理科学を活用した研究によってこの現象がストレスに対する生体の応答特性の調節に重要であることを解明した。また、癌や炎症などの疾病におけるMAPK経路の異常を解明し、新たな診断・治療法開発の基盤となる成果を得た。