Mathematical analysis of biological signaling networks across multiple layers

2021 Fiscal Year Final Research Report

• Project Area: Integrative understanding of biological signaling networks based on mathematical science
• Project/Area Number: 16H06577
• 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: Kyushu University
• Principal Investigator: Kubota Hiroyuki 九州大学, 生体防御医学研究所, 教授 (40376603)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: 数理解析 / トランスオミクス解析 / インスリン / 肥満

Outline of Final Research Achievements

We focused on the insulin signaling pathway and conducted mathematical analysis and multi-omics analysis at the individual level. In the mathematical analysis, we developed the first mathematical model of hormone action in vivo and revealed that the insulin signaling pathway in the liver processes information encoded into the blood insulin patterns and its mechanism. Using the model, we also predicted the insulin signaling pathway responses in type 2 diabetes mellitus conditions, and the model deepened our understanding on T2DM mechanisms. In the multi-omics analysis, we obtained time-series data across four omics layers, such as metabolome, phospho-proteome, expression proteome, and transcriptome. Also, we found that insulin action is coordinately regulated at different timing by reconstructing the trans-omic network across multi-omic layers.

Free Research Field

システム生物学

Academic Significance and Societal Importance of the Research Achievements

これまでの分子メカニズムに注目したシステム生物学の研究は、培養された細胞などを用いた解析が中心であった。我々は個体における肝臓のインスリン作用に注目し研究を行った。その結果、数理モデルでは世界で初めて生体内におけるホルモン作用の数理モデルを作成した。また、代謝・タンパク質リン酸化・タンパク質発現・遺伝子発現の4階層のオミクスデータから多階層に跨るネットワークを再構築し、協調的な制御機構を明らかにした。これらの個体を用いた研究は、今後のヒトに対する治療や創薬研究を推し進めると期待される。