| 研究課題/領域番号 |
20K09819
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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 |
CHIANG WeiChieh 沖縄科学技術大学院大学, 神経発生ユニット, スタッフサイエンティスト (70867754)
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| 研究期間 (年度) |
2020-04-01 – 2024-03-31
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| キーワード | ER stress / ER proteostasis / retina |
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| 研究実績の概要 |
ER membrane protein complex (EMC) is an important factor for ER homeostasis maintenance and membrane protein biogenesis. Using an EMC-deficient zebrafish model, I found that mutant fish display various retinal phenotypes, including the loss of photoreceptor cells and lack of visual function. Additionally, an EMC-deficient zebrafish carrying a reporter gene that monitor UPR activation in real time, I found that UPR is activated as early as 3 days post fertilization (dpf). This finding is further confirmed with bulk RNA sequencing analysis and qPCR analysis. These data suggest that ER stress and UPR may play a critical role in regulating retinal degeneration associated with EMC-dysfunction.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
To assess the global stress response induced by EMC-deficiency, I have performed the bulk RNA sequencing analysis of the EMC-deficient zebrafish eyes, followed by validation using qPCR analysis . I found that ER stress response/UPR is strongly activated up to 6 dpf. Interestingly, UPR activity starts to decline at 7 dpf with some part of PERK pathway still activated. I also identified genes, involved in cell death mechanisms, are up- or down-regulated. These data will provide insights on how ER stress regulates retinal degeneration associated with EMC-deficiency.
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| 今後の研究の推進方策 |
Since I have identified genes that may be involved in EMC-deficiency associated retinal degeneration, I am generating over-expression or CRISPR/Cas9 KO zebrafish of these genes to investigate how these genes modulate retinal cell death in the EMC-deficient fish. I will also perform gene expression analysis to determine how these genes are regulated by UPR. These studies will provide novel evidence on how UPR facilitate cell death mechanism in the retinas that suffer from the disruption of ER proteostasis.
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| 次年度使用額が生じた理由 |
For FY2022, I will use the grant for many research reagents such as antibodies and molecular biology kits. I will also purchase some essential small instruments necessary for the project.
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