Dissection and reconstitution of ultradian genetic oscillators responsive to dynamic signaling inputs

• Project/Area Number: 15H05326
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Life / Health / Medical informatics
• Research Institution: Kyoto University
• Principal Investigator: Isomura Akihiro 京都大学, ウイルス・再生医科学研究所, 共同研究者 (70512466)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000); Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
• Keywords: 遺伝子発現振動 / 光遺伝学 / 人工遺伝子回路 / 合成生物学 / 非線形動力学 / システム生物学 / 生物物理

Outline of Final Research Achievements

We studied dynamic responses of Hes1 genetic oscillators via optogenetic perturbation and single-cell imaging analysis. We found that Hes1 oscillators can decode dynamic signaling inputs at the single-cell level. We also succeeded in the visualization of single-cell phase response curves. Numerical simulations suggested that stochastic phase model is sufficient to explain synchronization processes of Hes1 oscillators upon external periodic perturbation.

Research Products

• [Journal Article] ES cell-derived presomitic mesoderm-like tissues for analysis of synchronized oscillations in the segmentation clock (2018)
  • Author(s): Matsumiya Marina、Tomita Takehito、Yoshioka-Kobayashi Kumiko、Isomura Akihiro、Kageyama Ryoichiro
  • Journal Title: Development Volume: 145 Issue: 4
  • DOI: 10.1242/dev.156836
  • NAID: 120006540184
  • Peer Reviewed / Open Access
• [Journal Article] Illuminating information transfer in signaling dynamics by optogenetics (2017)
  • Author(s): Isomura Akihiro、Kageyama Ryoichiro
  • Journal Title: Current Opinion in Cell Biology Volume: 49 Pages: 9-15
  • DOI: 10.1016/j.ceb.2017.11.002
  • Peer Reviewed
• [Journal Article] Optogenetic perturbation and bioluminescence imaging to analyze cell-to-cell transfer of oscillatory information. (2017)
  • Author(s): Isomura, A., Ogushi, F., Kori, H., and Kageyama, R.
  • Journal Title: Genes & Development Volume: 31 Issue: 5 Pages: 524-535
  • DOI: 10.1101/gad.294546.116
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis. (2016)
  • Author(s): Shimojo H, Isomura A, Ohtsuka T, Kori H, Miyachi H, Kageyama R
  • Journal Title: Genes Dev. Volume: 30 Issue: 1 Pages: 102-116
  • DOI: 10.1101/gad.270785.115
  • NAID: 120005980896
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 遺伝子発現リズムの細胞間位相同期の再構成 (2017)
  • Author(s): 磯村 彰宏
  • Organizer: 定量生物学の会 第八回年会
  • Place of Presentation: 自然科学研究機構 岡崎コンファレンスセンター
  • Year and Date: 2017-01-08
• [Presentation] 光遺伝学による遺伝子発現リズムの細胞間情報伝達機構の解明 (2016)
  • Author(s): 磯村 彰宏
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
  • Invited
• [Presentation] Interrogating oscillatory gene expression by optogenetics (2015)
  • Author(s): Akihiro Isomura
  • Organizer: International Symposium on Synthetic Systems Biology Joint 14th Symposium of Biochemical Systems Theory (BST2015)
  • Place of Presentation: 福岡
  • Year and Date: 2015-09-17