Grant: $239,915 - National Institutes of Health - Sep. 9, 2009
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Award Description: Germ cells are specialized cells that undergo mitotic proliferation followed by meiosis and cellular differentiation to generate haploid gametes for sexual reproduction. Errors in human germ cells are quite common and result in a high frequency of spontaneous abortions and aneuploid progeny (e.g., Down, Turner and Klinefelter’s Syndrome). Surprisingly, checkpoint control appears to be less efficient in the human female germ line; it has been proposed that this is one reason for the high frequency of defects associated with human female gametes. Here, we are taking advantage of the unique structural organization of the Caenorhabditis elegans germ line, the molecular genetics of the system, and the high degree of conservation with genes and pathways in humans to determine the molecular basis for differential germ-line checkpoint function between the sexes. To tackle this important problem, we are using a multi-pronged approach that relies on the strengths of C. elegans as a model for investigating sex-specific germ-line checkpoint function. To that end, we are determining how males prevent checkpoint-activated germ-line apoptosis and whether such absence leads to a high incidence of aneuploid gametes by monitoring the status of checkpoint and apoptotic proteins and examining the viability of progeny from reciprocal crosses when meiosis is impaired in only one of the sexes. We are investigating how meiotically-induced double strand breaks are repaired on a single X chromosome without eliciting a checkpoint response by monitoring the loading and disassembly of chromosomal axis and central region components of the synaptonemal complex on the male X, and probe the relationship between chromatin structure and checkpoint activation. An understanding of this process in the genetically tractable worm system may provide insight into why human female meiosis has less efficient checkpoint control, contributing to the high rate of errors. These studies will also provide new and important information on general mechanisms of checkpoint control, processes in which defects are central to the developmental of human cancers.
Project Description: The award commenced on September 17, 2009. In that short period we have concentrated our efforts on identifying personnel to hire. Additionally, we have focused on analysis of meiotic double strand break repair on the male X chromosome and have also begun to probe the relationship between chromatin and chromosome structure and checkpoint activation.
Jobs Summary: Award of the funds enabled the retention of a Junior Support Specialist and a graduate student. I am currently looking to hire another person. (Total jobs reported: 0)
Project Status: Less Than 50% Completed
This award's data was last updated on Sep. 9, 2009. Help expand these official descriptions using the wiki below.