Collaborative Research: Revealing essential regulatory proteins in tardigrade cryptobiosis

合作研究：揭示缓步动物隐生中的必需调节蛋白

• 批准号: 2149172
• 负责人: Leslie Hicks
• 金额: $ 68.23万
• 依托单位: University of North Carolina at Chapel Hill
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2149172&HistoricalAwards=false
• 关键词: Collaborative; Research; Revealing; essential; regulatory

Tardigrades (water bears) are eight-legged, microscopic invertebrates renowned for their ability to survive extreme stress. The hallmark of this survival is their unique ability to form a ‘tun,’ a survival state achieved through withdrawing of limbs, expelling internal water stores, and significantly decreasing metabolism. Tardigrades can remain in this state for years while remaining relatively undamaged, emerging only when the external threat has been removed. However, how this survival is regulated is largely unknown. The investigators' work has revealed a dependence of tardigrade survival on the presence of highly reactive oxygen-containing chemicals, small cellular messengers present in all living systems. These chemicals are essential signaling molecules that alter metabolic activity through the modification of proteins within the cell. The multidisciplinary team of scientists from the University of North Carolina at Chapel Hill and Marshall University can track these signals and affected biological compounds within tardigrades through powerful analytical and biochemical methods. The investigator team will combine these approaches to comprehensively map the entrance and emergence of tardigrade into and from tun across unique stresses allowing them to determine the precise adaptations that enable extreme stress tolerance. This work is integral to understanding molecular strategies for extreme stress tolerance within cells that can be applied to understand stress across life on earth. The collaborative teams will create sister courses on their campus, working across institutions to characterize different tardigrade proteins. In addition, students will be engaged in undergraduate research and gain experience in protein chemistry, computational modeling, and scientific literacy.Tardigrades (water bears) are cosmopolitan microscopic invertebrates that respond quickly to environmental stressors using ingenious modes of extremotolerance collectively known as cryptobiosis. Understanding the regulatory processes governing tardigrade cryptobiosis is essential to revealing the molecular strategies that preserve biochemical pathways when exposed to extreme stress. While cryptobiosis is prevalent across taxa, there exists only a nascent understanding of the molecular mechanisms and to what extent different types are interconnected. We are far from a comprehensive understanding of the biochemical participants, the coordination among diverse networks, or of the interplay between stress and survival. A multi-disciplinary team will combine their expertise in proteomics and reactive oxygen species monitoring with the aim of elucidating the redox-dependence of tardigrade extremotolerance. They will characterize tardigrade survival on both a physiological and proteomic level, enabling enhanced understanding of the molecular mechanisms through which tardigrades survive various hostile environments. Project outcomes include: a) the identification and characterization of essential redox-modified proteins required for cryptobiosis induction; b) the mapping of redox signaling across distinct cryptobioses; and c) the identification of key regulatory points in the tardigrade ‘cryptobiome’. This work will generate the most comprehensive biomolecular framework for cryptobiosis, to date.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

水熊是一种八条腿的微小无脊椎动物，以其承受极端压力的能力而闻名。这种存活的特点是它们独特的能力，形成了一种通过收回四肢、排出体内储存的水分和显著降低新陈代谢来实现的生存状态。迟滞可以在这种状态下保持多年，同时保持相对完好无损，只有在外部威胁消除后才会出现。然而，这种生存是如何受到监管的，在很大程度上是未知的。研究人员的工作揭示了迟发性生存依赖于高活性含氧化学物质的存在，这些化学物质是存在于所有生命系统中的小细胞信使。这些化学物质是重要的信号分子，通过修改细胞内的蛋白质来改变新陈代谢活动。来自北卡罗来纳大学教堂山分校和马歇尔大学的多学科科学家团队可以通过强大的分析和生化方法跟踪这些信号和迟滞内受影响的生物化合物。研究小组将结合这些方法，全面绘制迟滞进入和离开TUN的独特压力的入口和出现情况，使他们能够确定实现极端压力耐受的精确适应。这项工作对于理解细胞内极端应激耐受的分子策略是不可或缺的，这些策略可以应用于了解地球上生命的应激。合作团队将在他们的校园里创建姐妹课程，跨机构合作来表征不同的迟滞蛋白。此外，学生将从事本科研究，并获得蛋白质化学、计算模型和科学知识方面的经验。缓步动物(水熊)是世界性的微型无脊椎动物，它们使用巧妙的极端耐受模式快速响应环境压力，统称为隐生生物。了解控制迟缓隐生生物的调控过程对于揭示在极端压力下保护生化途径的分子策略是至关重要的。虽然隐生生物作用在各分类群中普遍存在，但对其分子机制以及不同类型之间的相互联系程度只有一个初步的了解。我们还远没有全面了解生化参与者、不同网络之间的协调，或者压力和生存之间的相互作用。一个多学科的团队将结合他们在蛋白质组学和活性氧物种监测方面的专业知识，目的是阐明延迟性极端耐受性的氧化还原依赖性。他们将在生理和蛋白质组水平上表征迟滞动物的生存，使人们能够更好地理解迟滞动物在各种恶劣环境中生存的分子机制。项目成果包括：a)确定和表征诱导隐生生物作用所需的基本氧化还原修饰蛋白；b)绘制不同隐生物体之间的氧化还原信号图谱；c)确定迟缓“隐生物群”中的关键调控点。这项工作将产生迄今为止最全面的隐生生物分子框架。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。