IntBIO: Collaborative Research: Functional Synergy Between Disordered Proteins and their Environment in Desiccation Protection

随着气候的变化，动植物越来越容易脱水。值得注意的是，进化出的一种帮助所有生命王国的生物体应对脱水的常见策略是通过合成一种特殊的蛋白质类别，即所谓的固有无序蛋白质。尽管它们在保护动植物不会枯竭方面很重要，但这些蛋白质是如何发挥作用的还没有解决。该项目将结合跨越单个分子到整个生物体的实验，以了解无序蛋白质如何在所有生命王国中提供防止脱水的保护。作为这项研究的一部分，该项目将通过远程学习从农村社区招募学生，并将他们纳入前沿的跨学科研究，以促进他们融入美国STEM劳动力队伍。所有生命王国的蛋白质组都包含相当一部分的序列，这些序列本质上是无序的，不采用稳定的三维结构。相反，这些序列存在于一个快速相互转换的构象集合中，这些构象对它们发挥作用的细胞环境的变化高度敏感。有趣的是，这些无序蛋白质中的许多都与环境胁迫的抗性有关，包括细胞的物理化学成分发生巨大变化的环境胁迫。这个项目的目标是全面了解无序的蛋白质和细胞环境是如何结合在一起，在极端干燥时为细胞提供保护的。为了实现这一目标，该项目将采用多层次、跨学科和综合的方法。从分子水平开始，将进行体外和计算实验，以深入了解干燥保护无序蛋白质如何在定义良好和可控的环境中发挥作用。这些信息将与在酵母(细胞水平)和多细胞动物模型(蛔虫、秀丽线虫、生物水平)中进行的无序蛋白质介导的干燥保护的高通量、基于测序的研究相结合。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。

As our climate changes, animals and plants are increasingly exposed to dehydration. Remarkably, a common strategy that has evolved to help organisms across all kingdoms of life deal with desiccation is through the synthesis of a special class of proteins known as intrinsically disordered proteins. Despite their importance in protecting animals and plants from drying out, how these proteins work is unresolved. This project will combine experiments that span individual molecules to whole organisms to understand how disordered proteins provide protection from dehydration across all kingdoms of life. As part of this study, this project will recruit students from rural communities via remote-learning and include them in cutting edge, interdisciplinary research which will facilitate their integration into the US STEM workforce. Proteomes across all kingdoms of life contain a significant fraction of sequences that are intrinsically disordered and do not adopt a stable three-dimensional structure. Instead, these sequences exist in an ensemble of rapidly interconverting conformations that can be highly sensitive to changes in the cellular environment in which they function. Interestingly, many of these disordered proteins are implicated in mediating resistance to environmental stresses, including desiccation, in which the physical-chemical composition of the cell changes dramatically. The goal of this project is to gain a holistic understanding of how disordered proteins and the cellular environment come together to provide protection to the cell during extreme desiccation. Towards this goal, the project will employ a multilevel, interdisciplinary, and integrated approach. Starting at the molecular level, in vitro and computational experiments will be performed that will provide insight into how desiccation-protective disordered proteins function in conjunction with well defined and controllable environments. This information will be integrated with high throughput, sequencing-based studies of disordered protein-mediated desiccation protection performed in yeast (cellular level), and a multicellular animal model (the roundworm, Caenorhabditis elegans, organismal level).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.