Opto-control of apoptosis and its molecular basis

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H05001
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Biophysics
• Research Institution: Kyoto University
• Principal Investigator: Nakasone Yusuke 京都大学, 理学研究科, 助教 (00613019)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 細胞死 / 光操作 / 分子間反応 / 過渡回折格子法 / LOVドメイン / Caspase8

Outline of Final Research Achievements

In recent years, the study of optogenetics and light-responsive molecules has become so popular that we are now able to manipulate diverse biological phenomena with light. Though this technology has led to the discovery of new molecular networks in neuroscience and many other fields, the signaling mechanisms has not been clarified at the molecular level in many cases. The main reason is the lack of sensitive and time-resolved methods for detecting intra- and inter-molecular reactions. In this study, we have established a new reaction detection method by combining a unique spectroscopic method (transient grating method) with various opto-control techniques. Using this method, we investigated the molecular mechanisms of apoptosis. We have also applied this method to light-responsive artificial molecules, promoting the elucidation of intermolecular reactions that have been difficult to detect using conventional techniques.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

アポトーシスは生命の恒常性の維持に必須であり、その異常は癌や脳機能障害など様々な疾患を引き起こす。本課題では、光で会合するタンパク質をアポトーシス誘導因子（Caspase8）に遺伝学的に結合したところ、光照射下でアポトーシスを起こす細胞数が増えることを確認した。これは副作用の少ない治療法の開発にも役立つ知見であるが、細胞死の誘導効率が低いため、実用化には今後の最適化が必要である。また光依存的な反応を分子レベルで捉える新手法の開発を行い、光会合反応や光応答性DNAの反応検出を実施した。この手法により未開拓であった様々な生体分子反応の解明が可能となるため、今後の生命科学研究への応用が期待される。