| Project/Area Number |
22K15103
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Lu Yonggang 大阪大学, ヒューマン・メタバース疾患研究拠点, 特任准教授(常勤) (00817033)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Fertilization / Sperm-egg fusion / Fusogen / Protein interaction / Spermatology / Spermiogenesis / Male infertility / Genome editing / Male reproduction / piRNA biogenesis / Cell biology / Sperm |
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| Outline of Research at the Start |
The study is subdivided into three major sections: 1) large-scale screening of molecules implicated in the sperm-egg fusion using the CRISPR/Cas9-based knockout strategy in mice; 2) in-depth functional analyses of the gamete fusion-required proteins using genetics, proteomics, and cell biology techniques; 3) detailed investigation of the gamete fusion machinery from different perspectives, such as species-specific recognition at sperm-egg fusion and the plasma membrane block to polyspermy.
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| Outline of Final Research Achievements |
During this project, I have made substantial progress in understanding the mechanism of mammalian fertilization and reproduction. From April 2022 to March 2024, I have published 5 first authored papers and 3 co-authored papers in international peer reviewed journals. These publications have (1) provided detailed mechanistic insights into mammalian sperm-egg fusion and novel strategies to study the molecular functions of fusion-required membrane proteins (Tang*, Lu* et al. 2022 PNAS), (2) marked the discovery of a novel protein biosynthesis pathway underpinning the biosynthesis of sperm proteins involved in fertilization (Lu et al. 2023 PNAS), and (3) deciphered the detailed structural and molecular mechanisms underlying zona pellucida block to polyspermy (Nishio et al. 2024 Cell).
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| Academic Significance and Societal Importance of the Research Achievements |
This work has significant relevance to the advancement of our knowledge of human reproduction and origin. It also provides profound implications for diagnosis and treatment of idiopathic male infertility and development of contraceptive measures involving molecular perturbations in fertilization.
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