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

该项目正在研究迟滞这种微生物如何缓解和适应地球气候变化的影响。迟滞可以在许多极端的环境中生存下来，包括干燥、高温和低温、辐射、渗透休克和压力。尽管迟滞的生存机制知之甚少，但有证据表明，生物保护性蛋白质的积累是它们生存的关键因素。这项研究项目着眼于迟滞动物中发现的几种生物保护性蛋白质的结构，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的迟滞动物中进行的测量。戴维斯博士将推进康涅狄格州的气候变化教育，并通过耶鲁科学之路项目支持的教育举措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，这项提案将支持对高中、本科生、研究生和研究生进行最先进仪器设备的培训，培养出准备帮助国家获得新知识的气候科学家，这些知识可以导致更可持续的地球。该奖项下的研究旨在对迟发性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有助于生物体迅速适应极端环境，这项工作的目标是揭开实现这一目标的机制。广泛的假设是迟滞无序蛋白通过不同的机制保护其他蛋白质，即防止聚集和去折叠，使迟滞能够在极端压力下生存。正在开发原位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延迟性无序蛋白质在基础条件和应激条件下的二级结构的差异。为了确定是否在原位形成相同的结构，将在体外、细胞内和活的迟滞动物中进行测量。互补的快速松弛成像测量将检查迟滞无序蛋白质如何在体外和在活的迟滞中改变其他蛋白质的结构和稳定性。综上所述，这项建议将提供对迟滞采用的抵抗气候变化和相关环境影响的基本过程的洞察。该奖项反映了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。

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.