Cellular Mechanisms for Quiescence in C. elegans

描述（由申请人提供）：实体瘤缺氧与治疗效果差和转移扩散相关。值得注意的是，这些肿瘤中的缺氧细胞通常是静止的。提出的研究旨在了解使用模型系统秀丽隐杆线虫在严重缺氧反应中实现静止的细胞机制。在缺氧的情况下，秀丽隐杆线虫进入一种极度静止的状态，即假死状态。为了确定在缺氧条件下存活的重要基因，将克隆不能在假死状态下存活的突变体中的缺陷基因。然后利用假死的细胞学标记来确定突变体的假死过程是如何异常的。当这些基因被确定后，它们在缺氧和常氧条件下的正常定位将被可视化，以评估每个基因在正常细胞中的作用。最后，为了剖析用于缺氧生存的机制，将监测每个突变体在响应外部氧水平时建立、维持和退出休眠的能力。总之，这些实验将有助于阐明在缺氧条件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.