Development of molecular recognition elements for understanding and regulation of biometal dynamics

2023 Fiscal Year Final Research Report

• Project Area: Integrated Biometal Science: Research to Explore Dynamics of Metals in Cellular System
• Project/Area Number: 19H05766
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: The University of Tokyo
• Principal Investigator: Tsumoto Kouhei 東京大学, 大学院工学系研究科(工学部), 教授 (90271866)
• Co-Investigator(Kenkyū-buntansha): 中木戸 誠 東京大学, 大学院工学系研究科(工学部), 助教 (80784511)
• Project Period (FY): 2019-06-28 – 2024-03-31
• Keywords: 生命金属科学 / 生物無機化学 / 金属細胞生物学 / 機能制御分子 / モダリティ / 分子認識 / 特異性 / 生命物理化学

Outline of Final Research Achievements

The aim of this research was to target various biometal-related proteins of pathogenic microorganisms and to create functional control molecules based on an understanding of the functional expression mechanism of each protein through precise analysis using various physicochemical methods. In microorganisms, biometal-related proteins are utilized, including proteins that function to acquire metals by acting on host metal-binding proteins. By utilizing various cutting-edge technologies through collaboration within the field, we have clarified the molecular mechanism of metal binding selectivity that overturns conventional wisdom, and created functionally inhibiting molecules in various modalities such as antibodies and low-molecular-weight compounds, through evaluation of the antibacterial activity and the drug efficacy in vivo model, and succeeded in achieving comprehensive results from the molecule to the individual.

Free Research Field

生命分子工学

Academic Significance and Societal Importance of the Research Achievements

生命金属に関連した蛋白質を標的として研究を行ってきたが、研究を進めていくにつれ、それら蛋白質が如何にして金属元素を識別しているか、その精緻な分子機構が明らかになり、蛋白質による分子認識について新たな知見をもたらした。それらの知見を踏まえ、本領域に携わる以前に比して、より多様な視点に基づく標的分子の機能を制御する分子を開発、論文や学会発表等を通じて発表・提案し、関連分野に大きなインパクトをもたらすともに、様々な背景を持つ班員との連携により、既存の学問分野の枠に収まらない融合研究が生まれ、低分子から改変抗体に至る各種機能制御分子が創出でき、創薬等社会実装につながる研究成果を多数上げることができた。