[RNW] - Gamete Interactions in Caenorhabditis elegans

[RNW] - 秀丽隐杆线虫配子相互作用

• 批准号: 10187604
• 负责人: ANDREW W. SINGSON
• 金额: $ 32.28万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10187604
• 关键词: Address; Affect; Animals; Area; Biochemical; Biological; Biological Models; Biological Process; Biology; Caenorhabditis elegans; Cell Communication; Cell membrane; Cells; Collection; Complement; Contraceptive Agents; Coupled; Embryo; Epidermal Growth Factor; Equipment and supply inventories; Event; Fertility; Fertility Study; Fertilization; Funding; Genes; Genetic; Genetic Screening; Germ Cells; Goals; Human; Immunoglobulins; Immunologics; Individual; Infertility; Lead; Ligands; Medical; Membrane Proteins; Methods; Modeling; Molecular; Molecular Analysis; Morphology; Mutation; Nature; Nematoda; Oocytes; Organism; Pathway interactions; Phenotype; Process; Proteins; Reporting; Research; Retinal blind spot; Role; Solid; Sperm Motility; Sperm-Ovum Interactions; Sterility; Work; conditional mutant; design; economic implication; egg; forward genetics; gene discovery; gene function; genetic analysis; genetic approach; genome sequencing; innovation; insight; molecular modeling; mutant; novel; novel strategies; positional cloning; receptor; reproductive; reverse genetics; screening; social implication; sperm cell; sperm function; sperm protein; success; tool; whole genome

RELEVANCE: Fertilization is biological process with important medical, social and economic implications. From extensive study, the events of fertilization are known in some detail. However, the molecular underpinnings of these events generally remain elusive. Most previous work on fertilization has relied on biochemical and immunological approaches. Our work is groundbreaking in the application of classic gentic analsysis to this vital area of research. RATIONALE: Many of the genetic and molecular tools developed for C. elegans are not available or are very difficult to utilize in other organisms traditionally used for studying fertilization. One of the most significant advantages of C. elegans is the ability to isolate and maintain mutants that affect sperm or eggs and no other cells. Previously, through the study of sterile mutants, we have identified some of the first molecules required for productive gamete interactions in C. elegans. We aim to get a better understanding how sperm molecules (SPE-13, SPE-36, and SPE-51) function to insure successful fertilization. The Izumo-like spe-45 and spe-51 genes represent conserved sperm function from worms to humans. Futher, a full understanding of the molecular mechanisms of fertilization is impossible without a more complete inventory of molecular components. Therefore we aim to identify new fertilization molecules through genetic and molecular analysis. Particular emphasis will be placed on the identification of genes required in oocytes. OBJECTIVES: The goal of this proposal is to further our understanding of fertilization in C. elegans by conducting the following experimental aims: 1) Investigate mechanistic connections, functions, and fertilization pathways of the gamete function molecules SPE-13, SPE-36, and SPE-51. 2) Conduct complementary forward and reverse genetic screens for fertilization mutants. We will take advantage of an innovative genetic screening strategy that enriches for gamete function mutants. 3) Determine the molecular nature of new gamete function genes defined by a fertilization defective mutant phenotype. This work will complement fertility studies in other organisms as well as provide insights into the mechanisms of cell-cell interactions and the diversity of reproductive strategies.

相关性：受精是一个生物学过程，具有重要的医学、社会 和经济影响。从广泛的研究中，受精事件是已知的， 一些细节。然而，这些事件的分子基础通常仍然存在， 难以捉摸。以前大多数关于受精的工作都依赖于生物化学和免疫学 接近。我们的工作是开创性的应用经典遗传分析， 这个重要的研究领域 原理：许多针对C. elegans 在传统上用于治疗癌症的其他生物体中是不可用的或很难利用的。 研究施肥。C. elegans是一种能力 分离和保持影响精子或卵子而不影响其他细胞的突变体。在此之前， 通过对不育突变体的研究，我们已经确定了一些第一批分子， 在C.优美的我们的目标是获得更好的 了解精子分子（SPE-13、SPE-36和SPE-51）如何发挥作用， 成功受精Izumo样spe-45和spe-51基因代表了保守的 从蠕虫到人类的精子功能。进一步，充分了解分子 如果没有一个更完整的分子清单， 件.因此，我们的目标是通过遗传学鉴定新的受精分子， 和分子分析。将特别强调基因的鉴定 卵母细胞所需的。 答：这项提案的目的是进一步了解 受精作用在C. elegans通过进行以下实验目的：1）调查 配子功能的机制联系、功能和受精途径 分子SPE-13、SPE-36和SPE-51。2)进行补充性的前进， 反向遗传筛选受精突变体。我们将利用创新的 基因筛选策略，富集配子功能突变体。3)确定 由受精缺陷定义的新配子功能基因的分子本质 突变表型这项工作也将补充其他生物体的生育力研究 为深入了解细胞间相互作用的机制和 生殖策略。