Genetic and Cellular Analysis of C. elegans Exposed to Anoxia

缺氧环境下线虫的遗传和细胞分析

• 批准号: 0344144
• 负责人: Pamela Padilla
• 金额: $ 38.86万
• 依托单位: University of North Texas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0344144&HistoricalAwards=false
• 关键词: Genetic; Cellular; Analysis; C.; elegans

Because eukaryotic organisms require oxygen for life it is probably not surprising that oxygen deprivation influences their growth and development. However, the absence of oxygen during development is not always fatal. It fact, several organisms, including nematodes, zebrafish, brine shrimp, and fruit flies arrest developmental and cell cycle progression in response to oxygen deprivation. The nematode, Caenorhabditis elegans, exposed to anoxia remarkably arrests developmental and cell cycle progression for up to 4 days. This arrest is reversible upon reexposure to oxygen, and is thus referred to as anoxia-induced suspended animation. The conservation of anoxia-induced suspended animation in eukaryotes suggests that reversible arrests have a significant role in organisms. However the phenomenon of anoxia-induced suspended animation has not been well studied and therefore is not understood, The proposed research focuses on how C. elegans embryos survive anoxia. The long-term research goal is to identify and characterize the molecular mechanisms that occur in nematodes to arrest developmental and cellular processes in response to anoxia. A combination of genetic and cell biological studies will be used to test the hypothesis that nematodes have developmentally dependent genetic and cellular mechanisms to survive anoxia. Genes required for nematodes to survive anoxia have been identified and will be further studied at the molecular level. Specifically, the role of spindle checkpoint genes, san-1 and mdf-2, in anoxia induced suspended animation will be investigated. Additionally, expansion of an RNA interference screen will be used to identify additional genes required for embryos to survive anoxia. The proposed project is significant because it will identify genetic pathways required for nematode embryos to survive anoxia. Understanding the effect oxygen deprivation has on organisms will lead to a greater understanding of how the environment effects developing embryos. Finally, the proposed project will integrate research and education by having the involvement of students at both the graduate and undergraduate level.

由于真核生物的生命需要氧气，缺氧影响它们的生长和发育可能并不奇怪。然而，发育过程中缺氧并不总是致命的。事实上，包括线虫、斑马鱼、丰年虾和果蝇在内的多种生物体都会因缺氧而阻碍发育和细胞周期进程。线虫，秀丽隐杆线虫，暴露于缺氧条件下，其发育和细胞周期进展显着停滞长达 4 天。这种停止在重新暴露于氧气时是可逆的，因此被称为缺氧引起的假死。真核生物中缺氧引起的假死的保存表明可逆停滞在生物体中具有重要作用。然而，缺氧引起的假死现象尚未得到充分研究，因此尚不清楚。拟议的研究重点是秀丽隐杆线虫胚胎如何在缺氧中生存。长期研究目标是确定和表征线虫中发生的分子机制，以阻止缺氧反应的发育和细胞过程。遗传和细胞生物学研究的结合将用于检验线虫具有发育依赖的遗传和细胞机制以在缺氧中生存的假设。线虫在缺氧环境下生存所需的基因已经被鉴定出来，并将在分子水平上进行进一步研究。具体来说，将研究纺锤体检查点基因 san-1 和 mdf-2 在缺氧引起的假死中的作用。此外，RNA干扰筛选的扩展将用于鉴定胚胎在缺氧环境中生存所需的其他基因。该项目意义重大，因为它将确定线虫胚胎在缺氧条件下生存所需的遗传途径。了解缺氧对生物体的影响将有助于更好地了解环境如何影响发育中的胚胎。最后，拟议的项目将通过研究生和本科生的参与来整合研究和教育。