Development and application of photoactivatable molecules for single-pathway activation

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19382
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 46:Neuroscience and related fields
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: Murakoshi Hideji 生理学研究所, 脳機能計測・支援センター, 准教授 (90608142)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: シグナル伝達 / 光応答性分子

Outline of Final Research Achievements

In this project, we aimed to establish a single-pathway imaging method by combining an optogenetic tool and fluorescence imaging techniques. We have developed a new photoactivatable kinase tool that is capable of selectively activating signaling pathways. Using two-photon excitation, we successfully activated the photoactivatable kinase. Furthermore, we combined the photoactivatable kinase with 2-photon fluorescence lifetime imaging microscopy, and successfully observed the photoactivatable kinase-dependent downstream protein activity at the level of single-synapses.

Free Research Field

生物物理、細胞生物、神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、新規の遺伝子コード型光応答性分子の開発に成功し、単一シナプスレベルで可塑的変化を惹起できた点で学術的意義が高い。さらにこの分子を2光子蛍光寿命イメージング顕微鏡システムを用いたFRETイメージングと組み合わせた。これにより、単一経路の分子活性化イメージングが組織深部でしかも単一シナプスレベルで可能になり、新たな分子イメージング法の開拓に成功した。