Cellular Mechanisms for Quiescence in C. elegans

描述（由申请人提供）：实体瘤中的缺氧与不良治疗结果和转移扩散相关。值得注意的是，这些肿瘤中的缺氧细胞通常是静止的。这项研究的目的是利用模型系统C来了解细胞在严重缺氧时达到静止的机制。优雅缺氧条件下，C.线虫进入了一种极度静止的假死状态为了确定在缺氧条件下生存的重要基因，将克隆不能在假死状态下生存的突变体中有缺陷的基因。然后利用假死的细胞学标记来确定假死过程如何在突变体中异常。当这些基因被鉴定后，它们在缺氧和常氧时的正常定位将被可视化，以评估每个基因的正常细胞作用。最后，为了剖析用于在缺氧条件下生存的机制，将监测每个突变体响应外部氧气水平而建立、维持和退出静止的能力。总之，这些实验将有助于阐明缺氧期间生存所需的机制和过程。

DESCRIPTION (provided by applicant): 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.