| 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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| 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 Annual 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. Among these publications, I would like to highlight 3 discoveries that are very important to the field of sperm-egg fusion. First, in collaboration with Stanford University, we elucidated the molecular function of TMEM95 in human fertilization (Tang*, Lu* et al. 2022 PNAS). Using innovative in vitro assays (such as sperm penetration assay, biolayer interferometry analysis, antibody inhibitory assay), we found that unlike IZUMO1, TMEM95 plays a critical role after sperm-egg binding and that sperm TMEM95 has a putative receptor on the egg plasma membrane. Second, I discovered a testis-specific, type-II transmembrane protein, 1700029I15Rik, that regulates the biosynthesis of acrosomal membrane glycoproteins involved in sperm-egg fusion (e.g., IZUMO1, SPACA6, EQTN; Lu et al. 2023 PNAS). This finding marks the discovery of a novel protein biosynthesis pathway underpinning the correct assembly of fertilization machinery during sperm development. Third, in collaboration with Karolinska Institutet, we deciphered the detailed structural and molecular mechanisms underlying zona pellucida block to polyspermy, which was a long-stand mystery in the field of fertilization.
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