Engineering synthetic cell-cell signaling that transmit dynamic information

• Project/Area Number: 18H03332
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 62010:Life, health and medical informatics-related
• Research Institution: Kyoto University
• Principal Investigator: Isomura Akihiro 京都大学, 高等研究院, 連携助教 (70512466)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: 合成生物学 / 人工遺伝子回路 / 光遺伝学 / 細胞間コミュニケーション / Notchシグナル / 分節時計

Outline of Final Research Achievements

We thought to build novel cell-cell signaling pathway that can transmit dynamic information in mammalian cells. We modified ligands and receptors of the synNotch signaling pathway, and found that the engineered pathway can transmit oscillatory information in sender cells to receiver cells.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、効率的な動的情報伝達を可能とする人工リガンド・人工受容体の選別プラットフォームが実現した。この技術の更なる進展によって、哺乳動物細胞の多細胞動態を人工遺伝子回路を使って制御・再構築することが可能になり、再生医療に資する人工多細胞組織の作製などの応用に繋がることが期待される。

Research Products

• [Journal Article] Dynamic Delta-like1 expression in presomitic mesoderm cells during somite segmentation (2020)
  • Author(s): Takagi Akari、Isomura Akihiro、Yoshioka-Kobayashi Kumiko、Kageyama Ryoichiro
  • Journal Title: Gene Expression Patterns Volume: 35 Pages: 119094-119094
  • DOI: 10.1016/j.gep.2019.119094
  • Peer Reviewed
• [Journal Article] Coupling delay controls synchronized oscillation in the segmentation clock (2020)
  • Author(s): K. Yoshioka-Kobayashi, M. Matsumiya, Y. Niino, A. Isomura, H. Kori, A. Miyawaki, R. Kageyama
  • Journal Title: Nature Volume: 580 Issue: 7801 Pages: 119-123
  • DOI: 10.1038/s41586-019-1882-z
  • Peer Reviewed
• [Journal Article] Oscillations of MyoD and Hes1 proteins regulate the maintenance of activated muscle stem cells (2019)
  • Author(s): Lahmann Ines、Brohl Dominique、Zyrianova Tatiana、Isomura Akihiro、Czajkowski Maciej T.、Kapoor Varun、Griger Joscha、Ruffault Pierre-Louis、Mademtzoglou Despoina、Zammit Peter S.、Wunderlich Thomas、Spuler Simone、Kuhn Ralf、Preibisch Stephan、Wolf Jana、Kageyama Ryoichiro、Birchmeier Carmen
  • Journal Title: Genes & Development Volume: 33 Issue: 9-10 Pages: 524-535
  • DOI: 10.1101/gad.322818.118
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Notchシグナルによる動的情報伝達の光制御と光計測 (2018)
  • Author(s): 磯村 彰宏
  • Organizer: 第41回日本分子生物学会年会
  • Invited
• [Remarks] 分節時計における同期発現振動の制御機構を解明
  • URL: https://www.infront.kyoto-u.ac.jp/achievements/post-5104/