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A03-1

多細胞-ECM の統合的な三次元力学動態の制御機構
Regulatory Mechanisms of Integrated Three-Dimensional Mechanical Dynamics of the Multicellular-ECM

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研究代表者 Research Leader 

長山 雅晴 (北海道大学 電子科学研究所附属社会創造数学研究センター, 教授)

Masaharu Nagayama (Professor, Research Institute for Electronic Science, Hokkaido University)

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胚発生やがんなど,立体組織・器官の三次元的な構造変化を伴う生命現象には,ECMと細胞の間の力学的な相互作用が重要である.本計画班では,このような立体組織内部における細胞-ECM間の力学相互作用を解明するため,ECMと多細胞の三次元動態を統合的に解析できる独自の数理モデルと,三次元組織内部の力学計測を組み合わせた研究手法を開発する.力学相互作用に加えて,オミクスデータ解析 (A03島村) 等に基づいた生化学相互作用を数理モデルに取り入れることによって「ECM−多細胞統合モデル」を開発する.開発したモデルを皮膚の毛包や乳腺 (A01藤原),血管組織 (A02山城),オルガノイド (A02永樂) 等に適用し,各器官形成メカニズムの解明に取り組む.さらに,数理モデルに含まれるECMの各種パラメータを数理モデル上で変化させることで,ECMのマルチモーダル情報の制御機構の理解に挑む.加えて,ここでの開発技術とハイドロゲル (A02鳴瀧) による多細胞動態の摂動実験とを組み合わせ,幹細胞オルガノイド (A02永樂) の動態予測を目指す.

Mechanical interactions between the ECM and cells are essential for biological phenomena involving three-dimensional structural changes in three-dimensional tissues and organs, such as embryogenesis and cancer. In order to elucidate such mechanical interactions between cells and the ECM inside three-dimensional tissues, this project group will develop a research method that combines an original mathematical model that enables integrated analysis of the three-dimensional dynamics of the ECM and multicell with mechanical measurements inside three-dimensional tissues. In addition to the mechanical interaction, we will develop an "ECM-multicellular integrated model" by incorporating biochemical interactions based on omics data analysis (A03 Shimamura) into the mathematical model. The developed model will be applied to skin follicles and mammary glands (A01 Fujiwara), vascular tissue (A02 Yamashiro), and organoids (A02 Eiraku) to elucidate the mechanisms of organogenesis. Furthermore, we will try to understand the control mechanism of multimodal information of ECM by changing various parameters of ECM included in the mathematical model on the mathematical model. In addition, we aim to predict the dynamics of stem cell organoids (A02Eiraku) by combining the technology developed here with perturbation experiments of multicellular dynamics using hydrogel (A02 Narutaki).

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