Development of a versatile chemogenetic protein inactivation method

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21250
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Nagoya Institute of Technology
• Principal Investigator: Tsukiji Shinya 名古屋工業大学, 工学(系)研究科(研究院), 教授 (40359659)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: タンパク質阻害 / 相分離 / タンパク質コンデンセート / ケモジェネティクス / オプトジェネティクス

Outline of Final Research Achievements

In this work we aimed to develop a new general chemogenetic method for controlling protein activity in living cells. By a modular combination of a tandem fusion of two oligomeric proteins with a chemically induced dimerization tool, we constructed synthetic protein condensates capable of recruiting and/or releasing proteins of interest in living mammalian cells in response to a small molecule. The condensate systems were applicable to control protein activity and cellular processes such as membrane ruffling and ERK signaling in a time scale of minutes.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究は、細胞内の任意のタンパク質の機能・活性を化合物で自在に制御・阻害する高汎用的な化学遺伝学技術を開発するものである。このような技術は、細胞や疾患のメカニズムの解明のためのツールとして有用であるばかりでなく、再生医療や細胞治療など、細胞機能の人工制御が基盤となるさまざまなバイオメディカル分野への応用が期待される。