Weighing the interactions made by Small Heat-Shock

Lead Research Organisation: University of Oxford
Department Name: Oxford Chemistry

Abstract

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, whereupon
further 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 found
in shallow reefs. This project aligns with the EPSRC portfolio themes of "physical sciences", and "living with environmental change".

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R513295/1 01/10/2018 30/09/2023
2285051 Studentship EP/R513295/1 01/10/2019 30/09/2022 Wiktoria Laura Sadowska