Generation of photoactivatable transcription molecules to control memory formation

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19377
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 46:Neuroscience and related fields
• Research Institution: Kyoto University
• Principal Investigator: Saneyoshi Takeo 京都大学, 医学研究科, 准教授 (00556201)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 遺伝子発現制御 / 記憶 / シナプス可塑性

Outline of Final Research Achievements

To control memory formation and its recall, it is important to have tools to manipulate gene expression for memory. We succeeded to generate a photo-inducible module, which allows any protein can be transformed into light-dependent nuclear localized protein. So far, we generated photoactivatable CREB and CaMKIV using the photo-inducible module. Although these photoactivatable molecules behaved as light-dependent nuclear localization, they showed a basal transcriptional activity without light. Because it might be due to leaky localization of overexpressed proteins in nucleus, we needed to reduce expression level by screening promoters or drug-mediated gene expression systems such as the TET-on/off.
We have established a method by which an AAV viral vector-mediated transducing protein into brain tissue through intravenous injection. Using this method, we could manipulate transcription by light after screening the promoter system to control expression for the photoactivatable proteins.

Free Research Field

記憶学習

Academic Significance and Societal Importance of the Research Achievements

本研究の光活性化型核内移行シグナルを利用すれば理論的にはどんなタンパク質でも光で核へ局在化できるため、構築にかかる試行錯誤を最小限にできる。この方法論により様々な核内シグナルを人為的に操作でき、新しい転写や染色体制御の発見につながると期待される。