Title Omitted

描述(由申请人提供)：本提案描述了一项针对老龄研究职业发展的培训计划。PI完成了线虫遗传学的博士后研究，在过去的三年里一直在运营一个研究减数分裂重组的小型实验室。这项建议满足了PI希望在她的实验室内开发一个新的研究计划的愿望，利用她已经拥有的减数分裂专业知识，并将其应用于生殖衰老的研究。培训计划将利用美国国家老龄化研究所的凯瑟琳·沃尔科夫博士和华盛顿大学的克里·科恩菲尔德博士的专业知识，他们积极研究线虫衰老的不同方面，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博士将分别在减数分裂和微阵列的活细胞成像方面提供技术培训。这项研究的重点是与衰老相关的线虫--秀丽线虫的生殖衰退。在线虫和人类中，配子形成过程中的染色体分离缺陷都会随着年龄的增长而出现。在女性中，这导致40岁前非整倍体卵母细胞显著增加(15倍)，而在男性中，精子数量减少。尽管这一领域的研究在临床上很重要，但人们对导致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。线虫的研究在衰老和减数分裂领域取得的巨大进展突显了利用这一系统来解决与种系衰老有关的基本问题。具体目标包括：1)研究线虫正常衰老过程中减数分裂的特征；2)分析衰老途径在种系衰老中的作用；以及3)识别对衰老信号做出反应的种系基因。卡内基研究所创造了一个促进科学家之间互动的环境，并为专业发展提供了机会，从而为年轻科学家的培训提供了一个极好的环境。此外，卡内基靠近国家老龄研究所，这将为PI提供更多机会，通过参加当地的无脊椎动物老龄化研究小组和参加该校园的研讨会，与老龄领域的科学家进行互动。这一培训计划应该会让PI在她为未来的学术生涯做准备的同时，在老龄化领域建立一个强有力的研究计划。

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.