The engineering of the novel imaging tools for neuromodulators

2023 Fiscal Year Final Research Report

• Project Area: Neural representation of "Death"
• Project/Area Number: 21H05142
• Research Category: Grant-in-Aid for Transformative Research Areas (B)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (III)
• Research Institution: The University of Tokyo
• Principal Investigator: Kato Hideaki 東京大学, 先端科学技術研究センター, 教授 (80805961)
• Project Period (FY): 2021-08-23 – 2024-03-31
• Keywords: GPCR / 神経調節因子 / クライオ電子顕微鏡 / 構造生物学 / タンパク質工学 / 神経科学

Outline of Final Research Achievements

To understand the complex functions of the brain, it is essential to have a detailed understanding of how neuromodulators control neural functions. One factor that makes understanding these control mechanisms difficult is the correspondence problem between neuromodulators and their receptors. This study aimed to develop molecular tools needed to address this issue. During the research period, we successfully determined the cryo-EM structure of neuromodulator receptors, thereby uncovering the structural basis for their recognition. Additionally, we developed molecular tools to unravel the mysteries of neuromodulator crosstalk, visualization tools for neuromodulator secretion, and new optogenetics tools to strongly advance the research of other labs within this research groups.

Free Research Field

構造生命科学

Academic Significance and Societal Importance of the Research Achievements

本研究で開発した分子ツールは、今後自閉症などの神経疾患の病態メカニズムを解明するための助けとなり得る他、受容体の構造情報は低分子薬の開発に繋がる可能性が期待される。