Genetic Analysis of Germ Cell Immortality

生殖细胞永生性的遗传分析

基本信息

批准号：
9033121
负责人：
SHAWN CAMERON AHMED
金额：
$ 29.6万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-17 至 2018-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9033121
关键词：
Adult Aging Animals Aplastic Anemia Atrophic Caenorhabditis elegans Cells Data Development Diapause Disease Double-Stranded RNA Ensure Epigenetic Process Evolution Fertility Fertility Disorders Functional disorder Generations Genes Genome Germ Germ Cells Goals Growth Health Homologous Gene Human Insulin Insulin-Like Growth Factor I Lead Light Link Longevity Longevity Pathway Mammals Mediating Modeling Mutation Nature Onset of illness Organism Pathway interactions Phenotype Process Proteins Pulmonary Fibrosis RNA Interference RNA analysis Regulation Reproduction Role Siblings Signal Pathway Signal Transduction Small RNA Somatic Cell Starvation Stem cells Sterility Stress Suppressor Mutations Telomerase Testing Toxic effect age related animation base biological adaptation to stress epigenome genetic analysis genome editing genome sequencing insight mutant neuronal cell body novel offspring piRNA programs reproductive research study response senescence sensor telomere tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Germ cells maintain themselves in a pristine condition that allows for indefinite proliferation as they are passed from one generation to the next. In contrast, somatic cells, including somatic stem cells, are only needed for a single generation and may 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. We discovered that the C. elegans Piwi homolog prg-1 promotes germ cell immortality via small RNA-mediated silencing of the epigenome and that the transgenerational fertility defect of Piwi/piRNA mutants can be suppressed by activation of a major somatic longevity pathway. We propose 1) to study how the insulin/IGF-1 signaling pathway suppresses the transgenerational fertility defect of Piwi mutants, 2) to study the sterilit phenotype of Piwi mutants, which may represent a state of suspended animation, and 3) to more thoroughly explore how the transgenerational sterility phenotype of Piwi mutants can be suppressed. The proposed experiments should provide insight into 1) a form of heritable epigenetic stress that can be transmitted by germ cells and 2) the organismal response to high levels of this stress. We could uncover fundamental principles relevant to transgenerational regulation of aging.

描述（通过应用程序证明）：生殖细胞在原始条件下保持不定限量，因为它们将一代生成一代，相比之下。确保人类增殖衰老的无限层的机制可能有助于某些与肿瘤相关的散发性，例如研究细菌通过无限的增殖性capace的机制。并且PIWI/PIRNA突变体的转世生育能力可以通过主要的体细胞寿命途径来抑制我们提出的1）研究胰岛素/IGF-1信号传导途径如何抑制PIWI突变体的THESG能源缺陷，2） Piwi mut的无菌表型，可能会压抑悬浮动画状态，3）更多剧院探索如何将Piwi Muttants的跨代无性无菌提供给SED的经验。通过细菌和2）对高水平压力的有机体反应。