Light-controllable transcription system for pancreatic cancer therapy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K15484
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Noda Natsumi 東京大学, 大学院理学系研究科(理学部), 特任研究員 (30624358)
• Co-Investigator(Renkei-kenkyūsha): OZAWA Takeaki 東京大学, 大学院理学系研究科, 教授 (40302806) ; TAKAORI Kyoichi 京都大学, 健康長寿社会の総合医療開発ユニット, 准教授 (10329485)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 遺伝子発現制御 / 光遺伝学 / Phytochrome B

Outline of Final Research Achievements

Pancreatic cancer is difficult to detect at an early stage and is a disease with a very poor prognosis. Therefore, it is desired to develop a new pancreatic cancer therapy. Spatiotemporal control of transcription using optogenetic tools may be a powerful technology for cancer therapy. We developed an optogenetic tool based on Arabidopsis thaliana phytochrome (Phy) B and its binding partner, phytochrome-interacting factor (PIF) 6. We generated a truncated PhyB, which allowed for reversible association with PIF6 by red/far-red light illumination. The red light illumination only for 5 min induced PhyB translocation from cytoplasm into the nucleus by the association with PIF6, resulting in transcriptional activation based on Gal4 DNA-binding domain and the upstream activating sequence of Gal system. The nucleocytoplasmic shuttling vector using PhyB and PIF6 may be applicable for transcriptional regulation in biological processes.

Free Research Field

生物発光プローブおよび光操作ツールの開発