DAZ GENES AND RNA BINDING IN HUMAN GERM CELL DEVELOPMENT

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Apart from how it is regulated by hormones, we know little about germ cell development in humans at a molecular level. Yet germ cell development is frequently aberrant, causing several common tumors and infertility in 10-15 percent couples worldwide. The overall goal of the research I propose is to gain a greater understanding of the genetic mechanisms of human reproduction, especially how germ cells are allocated and/or maintained in the early embryo. My approach to investigate this process is to explore the role of the DAZ (Deleted in AZoospermia) family of proteins and their RNA target(s) in early germ cell development since much evidence suggests these proteins function in early germ cell allocation and/or maintenance. I will determine what RNA molecules interact with DAZ protein and by what mechanism (for example, transcriptional activation, translational repression, or modulation of the cell cycle) DAZ assures that allocation or maintenance of germ cell populations occurs. Specifically, my aims are to: 1. Identify the RNA substrates to which the DAZ proteins bind. 2. Characterize the gene(s) encoding the RNA substrate(s) for DAZ family proteins. 3. Screen for mutations in infertile men and determine the phenotypes associated with mutations of the RNA substrate(s).