Identification and analysis of novel tardigrade stress response mechanisms

摘要 细胞稳定性对于在极端环境中生存至关重要。一些细胞和有机体可以在 即使在它们的组成部分不稳定的环境中，这表明细胞保护剂必须 存在着允许在这些情况下生存的东西。这种保护剂有可能被用于生物医学 像稳定敏感生物材料这样的应用，以及它们发挥作用的机制是 基本的生物学利益。这项提案的目标1试图确定迟发性疾病中的细胞保护剂。 迟滞是一种无脊椎动物，可以承受各种不同的环境压力，包括 干燥、冻结、辐射、高压，甚至太空的真空。以前的工作已经发现了一种 数量有限的迟滞保护性蛋白，值得注意的是，这些蛋白可以赋予对 细菌和酵母中的干燥和人类细胞中增强的辐射耐受性。这些研究奠定了 筛选新型迟滞应激保护蛋白的基础工作。从这一点确定的利益保护者 Screen也将在人类细胞培养中表达，以研究细胞稳定的机制 建立，并确定蛋白质是改善生物样品稳定性的有力候选者。这个 这项提议的第二个目的是揭示滞育的遗传调控--一种发育暂停的状态 并提高了对压力的抵抗力--在迟滞状态下。控制滞育的途径也可能调节 压力保护剂的生产。因此，鉴定保守的细胞信号通路所需的 滞育将为未来寻找保护剂的研究提供信息。这项工作的完成将导致确认 新型保护剂分子和抗逆机制可能被证明对以下应用有用 生物材料的储存。

Abstract Cellular stability is essential for surviving extreme environments. Some cells and organisms can survive in environments even in which their constituent parts are not stable, suggesting that cellular protectants must exist that allow for survival in these contexts. Such protectants have the potential to be utilized for biomedical applications like stabilizing sensitive biological materials, and the mechanisms by which they function are of fundamental biological interest. Aim 1 of this proposal seeks to identify cellular protectants in tardigrades. Tardigrades are invertebrates that can withstand a remarkable variety of environmental stresses including desiccation, freezing, radiation, high pressure, and even the vacuum of space. Previous work has identified a limited number of tardigrade protectant proteins, and remarkably these proteins can confer resistance to desiccation in bacteria and yeast and enhanced radiotolerance in human cells. These studies lay the groundwork to screen for novel tardigrade stress protectant proteins. Protectants of interest identified from this screen will also be expressed in human cell culture in order to study mechanisms by which cellular stability is established, and to identify proteins that are strong candidates for improving stability of biological samples. The second aim of this proposal is to uncover genetic regulation of diapause – a state of suspended development and increased stress resistance – in tardigrades. The pathways that control diapause may also regulate production of stress protectants. Therefore, identification of conserved cell signaling pathways required for diapause will inform future studies searching for protectants. Completion of this work will lead to identification of novel protectant molecules and mechanisms of stress resistance that may prove useful for applications like storage of biomaterials.