Genetic Analysis of Germ Cell Immortality

描述（由申请人提供）：生殖细胞旨在保持有效的无限增殖能力，以实现其生物学目的：无限期地从一代传递到下一代。相比之下，体细胞，包括体干细胞，只需要一代。因此，体细胞可能缺乏确保无限增殖能力的机制。生殖细胞和索马细胞之间的这种二分法可能是人类增殖性衰老的最终原因，并可能导致一些与年龄相关的疾病，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C。已经分离出了在生殖细胞永生方面受到损害的秀丽线虫致命生殖系突变体。有限数量的致命生殖系突变体将被绘制遗传图谱和克隆。这些致命的种系突变体的表型将被表征，促进生殖细胞永生的机制将被研究。将通过构建双突变体进行途径分析，这应该揭示不同形式的增殖性损伤如何在体内相互作用。将对一些C.线虫致命生殖系突变体。该项目利用正向遗传学研究整个动物生殖细胞增殖永生的分子基础。这个项目将确定一些基因和几个途径，除了端粒酶，抑制生殖细胞的增殖老化。其中一些基因或途径可能在哺乳动物体细胞中存在缺陷，因此可能会影响我们的衰老。

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.