Aging and Meiosis in the Nematode Germline

描述（由申请人提供）：本提案描述了一个培训计划，为发展职业生涯的老龄化研究。PI在C完成了博士后研究。在过去的三年里，他经营着一个研究减数分裂重组的小实验室。这个提议满足了Pi在她的实验室内开发一个新的研究项目的愿望，利用她在减数分裂方面已经拥有的专业知识，并将其应用于生殖衰老的研究。该培训项目将借鉴国家老龄化研究所的凯瑟琳·沃尔科博士和华盛顿大学的克里·科恩菲尔德博士的专业知识，他们积极研究C。以及卡内基研究所的道格·科什兰博士，他是染色体行为领域的领导者。此外，NIDDK的Andy Golden博士和Valerie Reinke博士将分别提供减数分裂和微阵列活细胞成像的技术培训。这项研究集中在线虫C.优雅配子形成过程中染色体分离的缺陷随着年龄的增长而出现。elegans优雅and humans人类.在女性中，这导致40岁时非整倍体卵母细胞的显著增加（>15倍），而在男性中，精子数量减少。尽管这一领域的研究具有重要的临床意义，但对减数分裂染色体分离保真度变化的潜在分子机制知之甚少。通过对C. elegans强调使用这个系统来解决与生殖细胞老化有关的基本问题。具体目的包括：1）研究了C. elegans; 2）分析衰老途径在生殖系衰老中的作用;以及3）鉴定响应衰老线索的生殖系基因。卡内基研究所为青年科学家的培训提供了一个极好的环境，创造了一个促进科学家之间互动的环境，并提供了专业发展的机会。此外，卡内基靠近国家老龄化研究所，将为PI提供更多的机会，通过参与当地的无脊椎动物老龄化研究小组和出席该校园的研讨会，与老龄化领域的科学家进行互动。该培训计划应允许PI在老龄化领域建立强大的研究计划，为她未来的学术生涯做准备。

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.