| Co-Investigator(Kenkyū-buntansha) |
牧 昌次郎 電気通信大学, 大学院情報理工学研究科, 准教授 (20266349)
小松 直貴 国立研究開発法人理化学研究所, 脳神経科学研究センター, 基礎科学特別研究員 (30737440)
下薗 哲 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (40391982)
阪上 朝子 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (90462689)
濱 裕 国立研究開発法人理化学研究所, 脳科学総合研究センター, 専門職研究員 (30261796)
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| Budget Amount *help |
¥241,930,000 (Direct Cost: ¥186,100,000、Indirect Cost: ¥55,830,000)
Fiscal Year 2019: ¥46,410,000 (Direct Cost: ¥35,700,000、Indirect Cost: ¥10,710,000)
Fiscal Year 2018: ¥46,540,000 (Direct Cost: ¥35,800,000、Indirect Cost: ¥10,740,000)
Fiscal Year 2017: ¥46,540,000 (Direct Cost: ¥35,800,000、Indirect Cost: ¥10,740,000)
Fiscal Year 2016: ¥46,410,000 (Direct Cost: ¥35,700,000、Indirect Cost: ¥10,710,000)
Fiscal Year 2015: ¥56,030,000 (Direct Cost: ¥43,100,000、Indirect Cost: ¥12,930,000)
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| Outline of Final Research Achievements |
Mitophagy removes dysfunctional mitochondria through lysosomal degradation. Thorough investigation of the behaviors and fates of fluorescent proteins inside lysosomes enabled us to develop an indicator for mitophagy. Large-scale image-based high-throughput screening led to the discovery of a hit compound that induces selective mitophagy of damaged mitochondria. In a mouse model of Parkinson’s disease, we found that dopaminergic neurons selectively failed to execute mitophagy that promoted their survival within lesions. We performed directed evolution of firefly luciferase using a red-shifted and highly deliverable luciferin analogue to establish AkaBLI, an all-engineered bioluminescence in vivo imaging system. AkaBLI produced 100 to 1,000-fold brighter emission in vivo than conventional systems, allowing non-invasive visualization of single cells inside deep internal organs of freely moving animals.
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