1) Unravel the molecular mechanism of testis-specific gene regulation during human spermatogenesis. In this project, we will try to discover the novel testis-specific genes in human testis by comparison of normal and defective sperm / testis samples using RNA-Seq technology. In the meanwhile, we will generate the gene knock-out mouse model using CRISPR/Cas9 technology to further verify the identified specific gene function in mice. The whole idea is reveal the molecular mechanism of the identified testis-specific gene regulation during spermatogenesis and provide a new conception for male infertility.
3) Discover the functions of non-coding RNAs (both small and large) and RNA-binding proteins in germ cell development. Using unbiased based RNA-Seq screen, we will identified large number of large/small non-coding RNA which are highly abundant in mouse/human reproductive organs (testes and ovaries). Then, we will take a systematic approach to generate "knock-out" mice deficient in a number of non-coding RNA using CRISPR/Cas9 technology, and further study the physiological role of those non-coding RNAs by "loss-of-function" strategies. At the same time, we will also be interested in regulation of sperm-borne non-coding RNAs, such as tRNA-derived small RNAs, miRNAs, lncRNA, in sperm-mediated transgenerational epigenetic inheritance.
Our overall goal is to understand the genetic and molecular basis of germ-line differentiation during spermatogenesis and oogenesis. This information is crucial to improve human reproductive and develop the efficient method for infertility therapy in human. Our long-term research objective is to understand the fundamental principles of human germline formation towards the genesis of high quality gametes. Our team’s next few research plans will be mainly focused on the following projects:
2) The mechanism of epigenetic regulation of histone-to-protamine transition during spermatogenesis. During spermiogenesis, the majority of the core histones are replaced sequentially, transition proteins and protamines. But the molecular mechanism is largely unknown. In this project, we will compare the histone modifications differences, including phosphorylation, acetylation, ubiquitination, etc., in sperm derived from fertile and infertile man, and further identified the unique histone modification. This project will aim to discover what histone modification will be turns to be abnormal in infertile man and to reveal the mechanism of epigenetic regulation of histone-to-protamine transition.
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