Cellular Mechanisms for Quiescence in C. elegans

描述(申请人提供)：实体肿瘤的缺氧与不良的治疗结果和转移扩散有关。值得注意的是，这些肿瘤中的缺氧细胞通常是静止的。这项拟议的研究旨在利用模型系统秀丽线虫了解在严重缺氧条件下实现静止的细胞机制。在缺氧的情况下，线虫进入极端静止的状态，暂停生命。为了识别对缺氧生存至关重要的基因，将克隆无法在暂停生命中生存的突变体中存在缺陷的基因。然后，将利用假死的细胞学标记来确定在突变体中，假死的过程是如何异常的。当基因被确定后，它们在缺氧和常氧状态下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，为了剖析用于缺氧生存的机制，将监测每个突变体建立、维持和退出静止状态的能力，以响应外部氧气水平。总之，这些实验将有助于阐明在缺氧状态下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.