Identification and analysis of novel tardigrade stress response mechanisms

新型缓步动物应激反应机制的识别和分析

• 批准号: 9893713
• 负责人: Jonathan Hibshman
• 金额: $ 6.53万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9893713
• 关键词: Animal Model; Bacteria; Biocompatible Materials; Biological; Caenorhabditis elegans; Candidate Disease Gene; Cell Culture Techniques; Cells; Cellular Stress; Cues; DNA; Data Set; Desiccation; Development; Developmental Process; Diapause; Engineering; Environment; Escherichia coli; Face; Fellowship; Freezing; Future; Genes; Genetic; Goals; Heat Stress Disorders; Human; In Situ Hybridization; Individual; Invertebrates; Ionizing radiation; Knowledge; Lead; Life; Molecular; Organism; Pathway interactions; Process; Production; Proteins; RNA; RNA Interference; Radiation; Regulation; Resistance; Resources; Saccharomyces cerevisiae; Sampling; Series; Signal Pathway; Signal Transduction; Stress; System; Testing; Time; Transcript; Vaccines; Vacuum; Work; Yeasts; bacterial resistance; biological adaptation to stress; cDNA Library; expression cloning; genetic analysis; improved; insight; interest; novel; pressure; resistance mechanism; response; transcriptome sequencing

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.

抽象的 细胞稳定性对于在极端环境中生存至关重要。一些细胞和生物体可以在极端环境中生存。 即使其组成部分不稳定的环境，这表明细胞保护剂必须 存在允许在这些情况下生存的保护剂有可能用于生物医学。 稳定敏感生物材料等应用及其发挥作用的机制 该提案的目标 1 旨在识别缓步动物的细胞保护剂。 缓步动物是无脊椎动物，可以承受各种不同的环境压力，包括 之前的工作已经确定了干燥、冷冻、辐射、高压，甚至太空的真空。 缓步动物保护蛋白的数量有限，并且不同寻常的是，这些蛋白可以抵抗 这些研究奠定了细菌和酵母的干燥以及人类细胞的放射性耐受性的增强。 筛选由此鉴定出的新型缓步动物应激保护蛋白的基础。 筛选也将在人类细胞培养物中表达，以研究细胞稳定性的机制 建立，并鉴定作为提高生物样品稳定性的有力候选蛋白质。 该提案的第二个目标是揭示滞育的遗传调控——一种暂停发育的状态 以及增强的抗应激能力——在缓步动物中，控制滞育的途径也可能受到调节。 因此，需要鉴定保守的细胞信号通路。 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鉴定。 新型保护剂分子和抗应激机制的研究可能对诸如 生物材料的储存。