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.
