| 研究課題/領域番号 |
21K06896
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分49020:人体病理学関連
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| 研究機関 | 沖縄科学技術大学院大学 |
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研究代表者 |
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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| 研究分担者 |
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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| 研究期間 (年度) |
2021-04-01 – 2022-03-31
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| 研究課題ステータス |
中途終了 (2021年度)
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| 配分額 *注記 |
4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2023年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
2022年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2021年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
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| キーワード | Parkinson's disease / Embryonic stem cell / Organoid / SNCA / GBA1 / alpha-synuclein / Pluripotent stem cell / Glucocerebrosidase |
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| 研究開始時の研究の概要 |
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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| 研究実績の概要 |
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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