| Project/Area Number |
21K06896
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Okinawa Institute of Science and Technology Graduate University |
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Principal Investigator |
Jo Junghyun 沖縄科学技術大学院大学, 行動の脳機構ユニット, スタッフサイエンティスト (50861126)
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| Co-Investigator(Kenkyū-buntansha) |
TAOUFIQ Zacharie 沖縄科学技術大学院大学, 細胞分子シナプス機能ユニット, スタッフサイエンティスト (10549348)
Arbuthnott Gordon 沖縄科学技術大学院大学, 行動の脳機構ユニット, 教授 (20455570)
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| Project Period (FY) |
2021-04-01 – 2022-03-31
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| Project Status |
Discontinued (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Parkinson's disease / Embryonic stem cell / Organoid / SNCA / GBA1 / alpha-synuclein / Pluripotent stem cell / Glucocerebrosidase |
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| Outline of Research at the Start |
The mutation of GBA1 encodes lysosomal enzyme GCase is implicated in PD, and its activity has been associated with synucleinopathy. The role of GBA1 mutations on synaptic dysfunction, consequent upon altered lipid composition at vesicle release and reuptake sites, are unclear. This research is to understand GCase induced pathology at synapses using state-of-the-art 3D brain organoid models combined with CRISPR/Cas9 genome engineering and proteomics analyses, and will identify novel factors, allowing the investigation of key mechanisms underlying the pathology in human neurons.
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| Outline of Annual Research Achievements |
As a Principal Investigator, Dr. Junghyun Jo decided to discontinue the KAKENHI project in early January 2022 because he resigned from his position at OIST, there were not much research achievements for about 10 months. Following the Specific Aim 1 for Year 1 and 2, he has successfully created hMLO-hSLO fusion organoid using wildtype and GBA1 human embryonic stem cells that showed reciprocal nigro-striatal and striato-nigral projections. Using the fusion organoid, he has validated the formation of synapses between dopaminergic neurons and GABAergic neurons at each area. Also, he confirmed the formation of alpha-synuclein aggregation in the fusion organoids.
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