Oxygen deprivation in solid tumors correlates with poor treatment outcome and metastatic spread. Notably, oxygen deprived cells in these tumors are often quiescent. The proposed research aims to understand cellular mechanisms for achieving quiescence in response to severe oxygen deprivation using the model system C. elegans. Upon oxygen deprivation, C. elegans enters a state of extreme quiescence, suspended animation. In order to identify genes important for surviving oxygen deprivation, genes defective in mutants that cannot survive suspended animation will be cloned. Cytological markers of suspended animation will then be utilized to determine how the process of suspended animation is aberrant in the mutants. When the genes have been identified, their normal localization during oxygen deprivation and in normoxia will be visualized to evaluate the normal cellular role of each gene. Finally, to dissect mechanisms used to survive oxygen deprivation, the ability of each mutant to establish, maintain, and exit from quiescence in response to external oxygen levels will be monitored. Together, these experiments will help elucidate mechanisms and processes that are required to survive during oxygen deprivation.
|Miller, Dana L; Roth, Mark B (2009) C. elegans are protected from lethal hypoxia by an embryonic diapause. Curr Biol 19:1233-7|