Aging and Meiosis in the Nematode Germline

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DESCRIPTION (provided by applicant): This proposal describes a training program for the development of career in aging research. The PI completed a post-doctoral fellowship in C. elegans genetics, and for the last three years has run a small lab studying meiotic recombination. This proposal addresses the Pi's desire to develop a new program of research within her lab, taking the expertise she already has on meiosis and applying it to the study of reproductive aging. The training program will draw on the expertise of Drs. Catherine Wolkow of the National Institute of Aging and Kerry Kornfeld of Washington University, who actively study different aspects of C. elegans aging, and Dr. Doug Koshland of the Carnegie Institution who is a leader in the field chromosome behavior. In addition, Dr. Andy Golden of NIDDK and Dr. Valerie Reinke will provide technical training in live cell imaging of meiosis and of microarrays, respectively. The research focuses on reproductive decline associated with aging in the nematode, C. elegans. Defects in chromosome segregation during gamete formation appear with age in both C. elegans and humans. In females, this leads to a significant increase (>15-fold) in aneuploid oocytes by age 40, and in males, a decrease in sperm count. Despite the clinical importance of research in this field, little is known about the underlying molecular mechanisms responsible for changes in the fidelity of meiotic chromosome segregation. The prodigous progress made in the fields of aging and meiosis by research in C. elegans underscores the use of this system to address fundamental questions related to germ line aging. The specific aims include: 1) characterizing meiosis during normal aging in C. elegans; 2) Analyzing aging pathways for their role in germ line aging; and 3) identifying germ line genes that respond to aging cues. The Carnegie Institution provide a superb setting for the training of young scientists by creating an environment that fosters interaction between scientists and by providing opportunities for professional development. In addition, the proximity of Carnegie to the National Institute of Aging will provide additional opportunities for the PI to interact with scientists in the aging field through participation in a local invertebrate aging research group and attendance at seminars on that campus. This training program should allow the PI to establish a strong research program in the aging field as she prepares for her future academic career.