| 研究課題/領域番号 |
23K19350
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| 研究種目 |
研究活動スタート支援
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| 配分区分 | 基金 |
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| 審査区分 |
0701:分子レベルから細胞レベルの生物学およびその関連分野
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| 研究機関 | 大阪大学 |
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研究代表者 |
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| 研究期間 (年度) |
2023-08-31 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
2,860千円 (直接経費: 2,200千円、間接経費: 660千円)
2024年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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| キーワード | ubiquitin code / protein aggregates / aging / E3 ligase |
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| 研究開始時の研究の概要 |
Protein misfolding and aggregation result in aging-related diseases. Ubiquitination regulates this process but the mechanism is unknown. We aim to decipher the ubiquitin codes on aggregates using mass spectrometry and nanobodies to identify therapeutic targets for aging and stress-related diseases.
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| 研究実績の概要 |
Protein misfolding, aggregation, and proteotoxic stresses contribute to cellular damage and disease. Ubiquitination plays a crucial role in maintaining protein homeostasis by removing toxic aggregates through the ubiquitin-proteasomal system and autophagy.
The purpose of this research is to elucidate the role of ubiquitin codes in toxic aggregate accumulation and help identify new therapeutic targets for age-related diseases to promote healthy aging.
We have found a unique ubiquitin code on toxic protein aggregates. We have established the role of a specific E3 ligase in protein aggregation under age-related stresses. We have generated and characterized unique nanobodies against the specific E3 ligase. We found that these nanobodies can modulate the formation and removal of toxic aggregates.
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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
We have been able to establish the association between a specific E3 ligase and the accumulation of toxic protein aggregates under stresses. We have also found a unique ubiquitin code on the toxic aggregates. With the use of unique nanobodies we have been able to modulate the formation and removal of protein aggregates in cells.
Due to these significant findings we have been able to establish our hypothesis and we are progressing according to the proposed plan. We are currently establishing the mechanism underlying the E3 ligase-mediated formation of aggregates.
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| 今後の研究の推進方策 |
So far we have been able to establish the association between a specific E3 ligase and the accumulation of toxic protein aggregates under stresses, and we have screened nanobodies to modulate toxic aggregate formation. Next we will elucidate the detailed mechanisms underlying these processes. Furthermore, we plan to use the nanobodies to identify potential targets that may be involved in aging stress-related toxic aggregate formation. With this information we will screen these potential targets in search of proteins that may mitigate the formation of toxic aggregates under stresses.
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