|
Germ cells are unique in that they are the only cell type in our bodies that is both totipotent and immortal. How germ cells in early embryos are formed and further developed into sperm and eggs remain one of the central questions in biology and a better understanding of this question could impact directly on our strategy in developing the diagnostic methods and treatment of diseases such as cancer, infertility and many other reproductive syndromes affecting men and women’s health. The overall goal of my research program is to understand the genetic and developmental mechanisms of mammalian germline development, in particular how key events such as maintenance/differentiation of germline stem cells and entry into meiosis are regulated in mammals. The pathways that develop germ cells appear to be conserved broadly, at least in outline, in organisms as diverse as insects and mammals. We proposed that there exists conserved core machinery that regulates the germ cell development and we wish to define the components of this underlying machinery through a combined evolutionary, genomic and genetic approach.
Through bioinformatics analysis, we are examining and comparing the known regulators for the germ cell development in both Drosophila and mice to identify conserved components. Using genomics and microarray tools, we performed whole-genome expression assay on Drosophila developing gonads and established the transcription profiles for fruitfly germ cell development. This transcription profiles are now being compared to the gene expression pattern of mouse germ cell development to identify novel conserved regulators with emphases on germline stem cell regulator and meiotic regulators. To examine the functions of those conserved regulators, we generate and characterize mouse knockout mutations disrupting the conserved stem cell and meiotic regulators in the lab. We are also exploring to use embryonic stem cell system as an in-vitro model for germ cell differentiation and to determine the roles of conserved regulators in germ cell differentiation through RNAi. It is our hope that our multi-prone approach will help us to unveil the underlying molecular machinery of germ cell development and to further our understanding on stem cell biology and reproductive biology.
|
