| 研究課題/領域番号 |
20K16262
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分49060:ウイルス学関連
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| 研究機関 | 金沢大学 |
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研究代表者 |
LIM KEE・SIANG 金沢大学, ナノ生命科学研究所, 特任助教 (60842987)
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| 研究期間 (年度) |
2020-04-01 – 2024-03-31
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| 研究課題ステータス |
交付 (2022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: 780千円 (直接経費: 600千円、間接経費: 180千円)
2022年度: 910千円 (直接経費: 700千円、間接経費: 210千円)
2021年度: 1,170千円 (直接経費: 900千円、間接経費: 270千円)
2020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 | SARS-CoV-2 spike protein / High-speed AFM / Neutralizing antibodies / COVID-19 / HS-AFM / Viral Fusion Protein / Viral fusion protein / fusogenic transition / exosome / Direct visualization / Virulence factors |
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| 研究開始時の研究の概要 |
HS-AFM is an ideal tool for investigating properties of viral fusion proteins that include native conformation, binding activity with host factors, and structural dynamic during fusogenic transition. Furthermore, interaction between fusion proteins and exosomes will be also be recorded.
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| 研究実績の概要 |
The objectives of this project are: 1) to record the native conformation viral fusion proteins under physiological conditions using HS-AFM; 2) to visualize the rapid and transient intermediates during conformational changes triggered by acidic conditions using HS-AFM; 3) to elucidate the conformational dynamic of viral fusion proteins when interacting with exosomes or antibodies using HS-AFM. The PI has implemented HS-AFM to perform nanoscopic elucidation of SARS-CoV-2 spike (S) protein structural dynamics during its interaction with neutralizing antibodies (Objective 3). Certain neutralizing antibodies promote the transition of RBD from its close conformation to open confirmation to enhance RBD-ACE2 interaction. This effect is known as antibody-dependent enhancement effect (ADE). This study reveals that HS-AFM could be worked as an efficient nanoscopic assessment platform for S NAb testing. This study has been published in a well-reputed journal, Nano Letters. Furthermore, this study has also been presented in several domestic conferences. Envelope protein (E protein) of Dengue virus will be investigated in the near future.
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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
SARS-CoV-2 fusion protein, spike (S) protein, has been actively studied to fulfill three main objectives of this project. First and second objectives have been achieved and published in a high impact journal, Journal of Extracellular Vesicles (Lim et al, J Extracell Vesicles, 2021). Recently, the third objective regarding the interaction between S protein and a neutralizing antibody has been published in Nano Letters (Lim et al, Nano Lett, 2023). Altogether, these research achievements indicated that the project is running rather smoothly.
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| 今後の研究の推進方策 |
Envelope protein (E protein) of Dengue virus will be investigated in the near future. HS-AFM will be applied: 1) to record the native conformation of E protein under physiological conditions using HS-AFM; 2) to visualize the rapid and transient intermediates during conformational changes triggered by acidic conditions using HS-AFM; 3) to elucidate the conformational dynamic of viral fusion proteins when interacting with exosomes or antibodies using HS-AFM.
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