Development of a red-light controllable gene expression system in combination with signal amplification approaches

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23716
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Kawano Fuun 東京大学, 大学院総合文化研究科, 助教 (20786090)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 光遺伝学 / 遺伝子発現制御 / 赤色光 / シグナル増幅法 / タンパク質工学

Outline of Final Research Achievements

We demonstrated that a developed system, which is a chimeric protein consisting of red-light photoreceptor phytochrome DrBphP derived from Deinococcus radiodurans, the LexA DNA binding domain, and the transcription factor VP16, can induce gene expression in a red-light illumination-dependent manner. In addition to that, we found that dark-leakiness associated with red-light photoswitch systems can be overcome by developing another system, which is a chimeric protein based on the red-light photoreceptor phytochrome Cph1 derived from Cyanobacteria.

Free Research Field

合成生物学

Academic Significance and Societal Importance of the Research Achievements

赤色光での光制御技術は，現在の光遺伝学において大部分を占める青色光での光制御技術の問題点である哺乳動物での生体組織透過性の低さを克服できる可能性を秘めている．本研究で開発した遺伝子発現制御技術は，組織透過性の高い赤色光に応答する光受容体を基盤としているため，生きた哺乳動物生体内で実用的な光遺伝学の技術として，臓器再生医療や様々な疾患治療法など，これまでの光遺伝学が応用困難であった未開拓の研究領域に応用する展開が期待される．