Weighing the interactions made by Small Heat-Shock

小热休克蛋白（sHSPs）是一种不依赖于atp的分子伴侣，通过抑制蛋白质的聚集来防止热应激细胞损伤。sHSPs与未折叠的蛋白质相互作用，并将其移交给atp依赖的伴侣蛋白，从而进一步加工恢复底物的天然结构。sHSP活性的机制需要进一步探索，以了解这种对所有生物都具有共同作用的细胞保护机制。这将影响我们对阿尔茨海默氏症等与蛋白质聚集有关的疾病的理解，以及暴露于环境变化的生物体的耐热性。本项目旨在分析热敏生物体中sHSPs、底物和其他伴侣蛋白之间的相互作用，以探索其活性机制。我将结合使用先进的质谱（MS）方法来量化蛋白质之间的相互作用，并探测它们的结构和动力学。该项目也为在溶液和真空中推进质谱技术识别蛋白质结构构象提供了机会，特别是气相氢-氘交换质谱，这是一个非常未开发的领域。该项目涉及与Elizabeth Vierling教授（马萨诸塞大学）合作，她是世界植物耐热性专家；以及阿德里安·史密斯教授（牛津大学动物学系），他是浅礁珊瑚蛋白质表达方面的专家。该项目符合EPSRC的“物理科学”和“与环境变化共存”的投资组合主题。

Small Heat-Shock Proteins (sHSPs) are ATP-independent molecular chaperones that prevent the heat stress cell damage by inhibiting proteins from aggregation. sHSPs interact with unfolded proteins and hand them over to ATP-dependent chaperones, whereuponfurther processing restores the native structure of substrates. The mechanisms of sHSP activity require further exploration to understand this mechanism of cell protection that is common to all organisms. This will impact on our understanding of diseases such as Alzheimer's associated with protein aggregation, as well as the thermo-tolerance of organisms exposed to environmental change. The aim of this project is an analysis of interactions between sHSPs, substrates, and other chaperones from heat-sensitive organisms in order to explore their mechanism of activity. I will use a combination of advanced mass spectrometry (MS) approaches to quantify the protein-protein interactions, and probe their structures and dynamics. This project is also an opportunity to advance MS techniques, both in solution and in vacuum, for identifying structural conformations of proteins, especially gas-phase Hydrogen-Deuterium Exchange MS, which is very unexplored.This project involves collaboration with Professor Elizabeth Vierling (University of Massachusetts), who is a world expert on plant thermo-tolerance; and Professor Adrian Smith (Department of Zoology, University of Oxford) and expert in protein expression in corals foundin shallow reefs. This project aligns with the EPSRC portfolio themes of "physical sciences", and "living with environmental change".