Genetics of Sperm Migration and Gamete Recognition In Caenorhabditis elegans

秀丽隐杆线虫精子迁移和配子识别的遗传学

• 批准号: 0544180
• 负责人: Steven L'Hernault
• 金额: $ 42万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0544180&HistoricalAwards=false
• 关键词: Genetics; Sperm; Migration; Gamete; Recognition

What is the intellectual merit of the proposed activity? This is a proposal to study the role of sperm during fertilization in the nematode Caenorhabditis elegans. C. elegans offers superior genetic and cell biological tools, so it is feasible to approach fertilization comprehensively. Seven mutants produce cytologically normal spermatozoa that are motile, but none can fertilize when they collide with an oocyte. The first cloned gene from this seven mutant group is spe-9, which encodes an epidermal growth factor (EGF) domain containing integral membrane protein important for sperm-oocyte recognition, adhesion or fusion. EGF repeat-containing proteins, like spe-9, are known to work with numerous other components. This proposal focuses on fer-14 and spe-42 genes that cause spe-9-like phenotypes. These genes have been cloned and the proposed studies will reveal how they participate in fertilization. The studies described in this proposal will clarify the genetic hierarchy that operates during C. elegans fertilization. FER-14 is a nematode specific protein, but SPE-42 has homologs in many multicellular animals, and the closest SPE-42 humans homolog is expressed in testes. C. elegans is presently the best organism for genetic analysis of fertilization and equivalent mutants affecting fertilization have not been described in any other metazoan. What are the broader impacts of the proposed activity? Several of the seven identified proteins that participate in C. elegans fertilization are evolutionarily conserved. SPE-9, SPE-41/TRP-3 and SPE-42 all have clear homologs in other multicellular animal and those homologs are expressed in human testes and other tissues. Cloned genes that participate in C. elegans fertilization all have orthologs in Caenorhabditis briggsae, so C. elegans is currently the best model for fertilization in other nematodes. Nematodes are major agricultural pests and 25% humans suffer from parasitic nematode infections, so any insight into how nematodes can be sterilized would have enormous practical value. In addition to this strength, general principles of cell-cell recognition, adhesion and fusion will also likely emerge from continued study of C. elegans fertilization. This laboratory has extensively integrated educational and diversity goals together with scientific advancement in the past and will continue to do so in the future

拟议活动的智力优点是什么？这是研究精子在线虫秀丽隐杆线虫中受精过程中的作用的建议。秀丽隐杆线虫提供了卓越的遗传和细胞生物学工具，因此可以全面接触受精是可行的。七个突变体产生了流动性的细胞学正常精子，但是当它们与卵母细胞碰撞时，没有人可以施肥。该七个突变组的第一个克隆基因是SPE-9，它编码了包含对精子型识别，粘附或融合的积分膜蛋白的表皮生长因子（EGF）结构域。众所周知，EGF重复蛋白（如SPE-9）可以与许多其他成分一起使用。该提案的重点是引起SPE-9样表型的FER-14和SPE-42基因。这些基因已被克隆，拟议的研究将揭示它们如何参与受精。该提案中描述的研究将阐明在秀丽隐杆线虫受精期间运作的遗传层次结构。 FER-14是线虫特异性蛋白，但是SPE-42在许多多细胞动物中具有同源物，并且最接近的SPE-42人类在睾丸中表达。秀丽隐杆线虫目前是对受精的遗传分析和影响受精的等效突变体的最佳生物体，在任何其他后生动物中尚未描述。拟议活动的更广泛影响是什么？参与秀丽隐杆线虫受精的七个确定的蛋白质中有几个在进化上是保守的。 SPE-9，SPE-41/TRP-3和SPE-42在其他多细胞动物中均具有明显的同源物，这些同源物在人类睾丸和其他组织中表达。参与秀丽隐杆线虫受精的克隆基因都在briggsae的Caenorhabditis中都有直系同源物，因此秀丽隐杆线虫目前是其他线虫中受精的最佳模型。线虫是主要的农业害虫，25％的人患有寄生线虫感染，因此，对如何对线虫进行消毒的任何见解都将具有巨大的实用价值。除了这种强度外，细胞细胞识别的一般原理，粘附和融合也可能会从继续研究秀丽隐杆线虫施肥中出现。该实验室已广泛整合教育和多样性目标以及过去的科学进步，将来会继续这样做