CAREER: Molecular mechanisms of tardigrade disordered proteins adapted to protect against environmental stress

职业：缓步动物无序蛋白质适应环境压力的分子机制

• 批准号: 2338323
• 负责人: Caitlin Davis
• 金额: $ 96.2万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-02-01 至 2029-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2338323&HistoricalAwards=false
• 关键词: CAREER; Molecular; mechanisms; tardigrade; disordered

The project is investigating how tardigrades, a microorganism, mitigate and adapt to the effects of Earth’s changing climate. Tardigrades can survive many environmental extremes, including desiccation, high and low temperatures, radiation, osmotic shock, and pressure. Although the survival mechanisms of tardigrades are poorly understood, evidence points towards accumulation of bioprotectant proteins as a key element to their survival. This research project looks at the structure of several bioprotectant proteins identified in tardigrades and how they protect other proteins when the environment becomes unsuitable for life. Carefully controlled experiments conducted in test tubes and in cultured cells will assist with the interpretation of measurements made directly in living tardigrades. Dr. Davis will advance the state of climate change education in Connecticut and nurture the next generation of interdisciplinary scientists and teachers through a scaffold of education initiatives supported by Yale’s Pathways to Science program. This work will target communities that are underprivileged and most vulnerable to climate impacts. In addition, this proposal will support the training of high school, undergraduate, postgraduate, and graduate researchers on state-of-the-art instrumentation, producing climate scientists prepared to help the nation obtain new knowledge that can lead to a more sustainable planet. The research under this award aims to develop a detailed physiochemical understanding of the structure and function of tardigrade disordered proteins. These families of proteins and other intrinsically disordered proteins assist organisms with rapidly adapting to environmental extremes and the goal of this work is to unravel the mechanisms that allow for this. The broad hypothesis is that tardigrade disordered proteins protect other proteins, i.e. prevent aggregation and unfolding, through distinct mechanisms that enable tardigrades to survive extreme stress. In situ infrared and fluorescence imaging techniques are being developed to accomplish two separate but related projects. Optical photothermal infrared imaging will reveal differences in the secondary structure of tardigrade disordered proteins under basal and stress conditions. To determine whether the same structures form in situ, measurements will be made in vitro, in cell, and in living tardigrades. Complementary fast relaxation imaging measurements will examine how tardigrade disordered proteins change the structure and stability of other proteins in vitro and in living tardigrades. Taken together, this proposal will provide insight into the fundamental processes that tardigrades employ to resist climate change and related environmental impacts.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.

该项目正在调查一种微生物缓步动物如何减轻和适应地球气候变化的影响。缓步动物可以在许多极端环境中生存，包括干燥，高温和低温，辐射，渗透压休克和压力。虽然对缓步动物的生存机制知之甚少，但有证据表明，生物保护蛋白的积累是其生存的关键因素。这个研究项目着眼于在缓步动物中发现的几种生物保护蛋白质的结构，以及当环境变得不适合生命时它们如何保护其他蛋白质。在试管和培养细胞中进行的仔细控制的实验将有助于解释直接在活体缓步动物中进行的测量。戴维斯博士将推进康涅狄格州的气候变化教育状况，并通过耶鲁大学科学之路项目支持的教育计划框架培养下一代跨学科科学家和教师。这项工作将针对贫困和最容易受到气候影响的社区。此外，该提案将支持高中，本科，研究生和研究生研究人员的最先进仪器的培训，培养气候科学家，帮助国家获得新的知识，可以导致一个更可持续的星球。该奖项下的研究旨在对缓步动物无序蛋白质的结构和功能进行详细的物理化学理解。 这些蛋白质家族和其他内在无序的蛋白质帮助生物体快速适应极端环境，这项工作的目标是解开允许这种情况的机制。广义的假设是，缓步动物的无序蛋白质保护其他蛋白质，即防止聚集和展开，通过不同的机制，使缓步动物生存的极端压力。正在开发现场红外和荧光成像技术，以完成两个独立但相关的项目。光学光热红外成像将揭示基础和应力条件下的缓步动物无序蛋白质的二级结构的差异。为了确定是否在原位形成相同的结构，将在体外，细胞和活的缓步动物中进行测量。互补的快速弛豫成像测量将研究缓步动物无序蛋白质如何改变体外和活体缓步动物中其他蛋白质的结构和稳定性。总之，这一建议将提供洞察的基本过程，缓步动物采用抵御气候变化和相关的环境影响。这一奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。