Study on phase separation to understand amyloid formation and development of additives

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19284
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Shiraki Kentaro 筑波大学, 数理物質系, 教授 (90334797)
• Co-Investigator(Kenkyū-buntansha): 菅井 祥加 東京工業大学, 国際先駆研究機構, 特任助教 (10905566)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: タンパク質 / 凝集 / 相分離 / アミロイド

Outline of Final Research Achievements

Proteins are characterised by their diverse states, including aggregation, phase separation, gelation and fibrilization. In particular, the change of state of proteins from droplets to aggregates has attracted much attention because it can lead to the elucidation of the causes of diseases. The aim of this study was to rationally control the phase separation and aggregation of proteins. Our results showed that they can be rationally understood by utilising phase diagrams. We also found that amyloid nucleation is slower in narrower spaces, that proteins folded into droplets become multiphase when they are incorporated, and that droplet size can be controlled by small molecule ATP.

Free Research Field

蛋白質溶液学

Academic Significance and Societal Importance of the Research Achievements

本研究では、タンパク質の凝集と相分離の状態変化を、どうすれば合理的に理解し、制御できるのかというタンパク質に固有の難しい課題にチャレンジした。古典的な相図を用いることで、相分離した状態を安定に保つ条件と、凝集へと成熟する条件が見分けられることがわかった。このようなタンパク質の凝集と相分離のメカニズムの理解が深まれば、バイオ医薬品の安定化や、食品タンパク質の性質の制御など、タンパク質に関連する産業に広く役立つ情報を提供できる。