Aging and Meiosis in the Nematode Germline

线虫种系的衰老和减数分裂

• 批准号: 8049140
• 负责人: JUDITH L YANOWITZ
• 金额: $ 11.43万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-15 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8049140
• 关键词: Address; Affect; Age; Aging; Aneuploidy; Animals; Behavior; Biological Assay; Biological Models; Caenorhabditis elegans; Candidate Disease Gene; Cell Nucleus; Cell division; Chromatin Structure; Chromosome Segregation; Chromosomes; Clinical; Cues; DNA biosynthesis; Defect; Development; Diploidy; Down Syndrome; Ensure; Environment; Enzymes; Event; Fellowship; Female; Fostering; Functional disorder; Future; Gene Conversion; Genes; Genetic; Genetic Materials; Genetic Nondisjunction; Genetic Recombination; Germ Cells; Germ Lines; Haploidy; Homologous Gene; Human; Imagery; Institutes; Institution; Invaded; Invertebrates; Knowledge; Lead; Length; Life; Longevity; Meiosis; Meiotic Prophase I; Meiotic Recombination; Meta-Analysis; Molecular; Molecular Genetics; Monosomy; National Institute of Diabetes and Digestive and Kidney Diseases; Nematoda; Oocytes; Pathway interactions; Postdoctoral Fellow; Principal Investigator; Process; Production; Program Development; Proteins; Proteomics; Protocols documentation; Reproduction; Research; Resected; Role; Running; Scientist; Signal Transduction; Sister Chromatid; Sperm Count Procedure; Synaptonemal Complex; System; Techniques; Testing; Therapeutic; Tissues; Topoisomerase; Training; Training Programs; Trisomy; Universities; Washington; Woman; age effect; age related; aging gene; career; cellular imaging; cohesion; egg; male; mutant; neuronal cell body; normal aging; programs; repaired; reproductive; scaffold

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.

描述（由申请人提供）：本提案描述了一项针对老龄化研究职业发展的培训计划。PI完成了秀丽隐杆线虫遗传学的博士后奖学金，并在过去三年中经营了一个研究减数分裂重组的小实验室。这个提议满足了Pi的愿望，即在她的实验室里开发一个新的研究项目，把她在减数分裂方面的专业知识应用到生殖衰老的研究中。培训计划将利用博士的专业知识。国家衰老研究所的凯瑟琳·沃尔科夫和华盛顿大学的克里·科恩菲尔德，他们积极研究秀丽隐杆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博士将分别提供减数分裂和微阵列活细胞成像的技术培训。这项研究的重点是线虫C.秀丽隐杆线虫与衰老相关的生殖能力下降。在秀丽隐杆线虫和人类中，配子形成过程中的染色体分离缺陷都随着年龄的增长而出现。在女性中，这导致40岁时非整倍体卵母细胞显著增加（约15倍），而在男性中，精子数量减少。尽管该领域的研究具有临床重要性，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。秀丽隐杆线虫研究在衰老和减数分裂领域取得的巨大进展强调了该系统用于解决与生殖细胞衰老相关的基本问题。具体目的包括：1)表征秀丽隐杆线虫正常衰老过程中的减数分裂；2)分析衰老途径在生殖细胞衰老中的作用；3)识别对衰老线索有反应的生殖系基因。卡内基研究所通过创造一个促进科学家之间互动的环境和提供专业发展的机会，为培养年轻科学家提供了一个极好的环境。此外，卡耐基靠近国家老龄化研究所，这将为PI提供额外的机会，通过参加当地无脊椎动物老龄化研究小组和参加校园研讨会，与老龄化领域的科学家进行互动。这个培训计划应该允许PI在老龄化领域建立一个强大的研究计划，为她未来的学术生涯做准备。