Light-controllable transcription system for pancreatic cancer therapy

• 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
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 遺伝子発現制御 / 光遺伝学 / Phytochrome B / 光受容体 / 癌 / ルシフェラーゼ / がん / 光制御 / 遺伝子発現 / 膵癌

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.

Research Products

• [Int'l Joint Research] リバプール大学生命科学/リバプール大学トランスレーショナルメディスン研究所(英国)
• [Journal Article] Dynamic Monitoring of p53 Translocation to Mitochondria for the Analysis of Specific Inhibitors Using Luciferase-fragment Complementation. (2017)
  • Author(s): Natsumi Noda, Raheela Awais, Robert Sutton, Muhammad Awais and Takeaki Ozawa
  • Journal Title: Biotechnology and Bioengineering Volume: 114 Issue: 12 Pages: 2818-2827
  • DOI: 10.1002/bit.26407
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Development of a bioluminescent probe to monitor p53 translocation into mitochondria using luciferase-fragment complementation assays. (2017)
  • Author(s): Natsumi Noda, Raheela Awais, Robert Sutton, Muhammad Awais, and Takeaki Ozawa
  • Organizer: 第11回バイオ関連化学シンポジウム、 第32回生体機能関連化学シンポジウム、第20回バイオテクノロジー部会シンポジウム
• [Presentation] Sustained monitoring of p53 translocation into mitochondria using luciferase-fragment complementation. (2017)
  • Author(s): Natsumi Noda, Raheela Awais, Robert Sutton, Muhammad Awais, and Takeaki Ozawa
  • Organizer: 2017年度生命科学系学会合同年次大会(第40回日本分子生物学会年会、第90回日本生化学会大会)