Structure, function and molecular interaction studies of membrane proteins important in mitochondrial energy metabolism

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Mitochondrial Uncoupling Proteins (UCPs) are a group of membrane proteins that impact on cellular energy metabolism. UCP1 occurs in specialised brown fat of mammals, where it acts to uncouple the process of oxidative phosphorylation in mitochondria to release energy as heat instead of making ATP. Activity of the protein helps protect against cold temperatures, but may also may help combat metabolic disease in humans. The related proteins, UCP2- 5, occur in various other tissues but are not well understood despite being implicated in metabolic disorders, inflammation, ischemic shock, cancer and aging.This project will focus on determining the core properties of UCP proteins to understand structure function relations and their biochemical roles, taking advantage of our advances in purifying and studying the molecular nature of UCP1. The research will cover a breadth of biochemical and molecular biology techniques applicable to membrane proteins (e.g. recombinant protein production and purification, chromatography methods, liposome reconstitution/transport assays, mutagenesis), including approaches to investigate membrane protein ligand binding and protein-protein interactions (e.g. protein thermostability shift anaysis, Surface Plasmon Resonance and Fluid Flow-Induced Dispersion Analysis).