Genetic Analysis of Germ Cell Immortality

生殖细胞永生性的遗传分析

• 批准号: 7899933
• 负责人: SHAWN CAMERON AHMED
• 金额: $ 27.04万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-17 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7899933
• 关键词: Affect; Age; Aging; Alleles; Animals; Biological; Caenorhabditis elegans; Cells; Disease; Ensure; Generations; Genes; Genetic; Genetic Complementation Test; Germ; Germ Cells; Germ-Line Mutation; Goals; Human; Longevity; Malignant Neoplasms; Maps; Mitotic; Molecular; Mutagenesis; Mutation; Nature; Oocytes; Pathway Analysis; Pathway interactions; Pattern; Phenotype; Positioning Attribute; Proteins; Resolution; Sequence Analysis; Single Nucleotide Polymorphism; Somatic Cell; Stem cells; Sterility; Telomerase; Temperature; Testing; Time; Tissues; Work; X Chromosome; age related; autosome; base; design; gene function; genetic analysis; in vivo; mutant; neuronal cell body; prevent; sperm cell; stem; tumorigenesis

DESCRIPTION (provided by applicant): Germ cells are designed to maintain an effectively unlimited proliferative capacity in order to fulfill their biological purpose: to be passed from one generation to the next, indefinitely. In contrast, somatic cells, including somatic stem cells, are only needed for a single generation. Somatic cells may therefore be deficient for mechanisms that ensure an unlimited proliferative capacity. This dichotomy between germ and soma cells may be the ultimate cause of human proliferative aging and may contribute to some age-related diseases such as tumorigenesis. The long-term goal of this project is to study the mechanisms by which germ cells maintain an unlimited proliferative capacity. Many C. elegans mortal germline mutants that are compromised for germ cell immortality have been isolated. A limited number of mortal germline mutants will be mapped genetically and cloned. The phenotypes of these mortal germline mutants will be characterized, and mechanisms that promote germ cell immortality will be investigated. Pathway analysis will be conducted by constructing double mutants, which ought to reveal how different forms of proliferative damage interact in vivo. The relationship between proliferative and post-mitotic aging will be studied for some C. elegans mortal germline mutants. This project utilizes forward genetics to study the molecular basis of the proliferative immortality of germ cells in whole animals. This project will define a number of genes and several pathways, aside from telomerase, that repress proliferative aging in germ cells. Some of these genes or pathways may be deficient in mammalian somatic cells and may therefore affect how we age.

描述（由申请人提供）：生殖细胞旨在维持有效的无限增殖能力，以实现其生物学目的：无限期地通过一代人将其传递到下一代。相比之下，只有一代人需要体细胞（包括体干细胞）。因此，体细胞可能缺乏确保无限增殖能力的机制。细菌和躯体细胞之间的这种二分法可能是人类增殖衰老的最终原因，并且可能导致某些与年龄有关的疾病，例如肿瘤发生。该项目的长期目标是研究生殖细胞保持无限增殖能力的机制。许多因生殖细胞永生而受到损害的秀丽隐杆线虫致命种系突变体已被分离出来。遗传和克隆将绘制有限数量的致命系种突变体。这些致命种系突变体的表型将被表征，并将研究促进生殖细胞永生的机制。途径分析将通过构造双突变体进行，该突变体应该揭示不同形式的增殖损伤如何在体内相互作用。对于一些秀丽隐杆线虫的致命种系突变体，将研究增生性和有丝分裂后衰老之间的关系。该项目利用远期遗传学来研究整个动物生殖细胞增殖不朽的分子基础。该项目将定义许多基因和多种途径，除了端粒酶，这些基因抑制了生殖细胞中增殖的衰老。这些基因或途径中的一些可能缺乏哺乳动物的体细胞细胞，因此可能会影响我们的年龄。