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

线粒体解偶联蛋白是一类影响细胞能量代谢的膜蛋白。UCP 1发生在哺乳动物的专门棕色脂肪中，在那里它的作用是解偶联线粒体中的氧化磷酸化过程，以释放能量作为热量，而不是制造ATP。这种蛋白质的活性有助于抵御寒冷的温度，但也可能有助于对抗人类的代谢疾病。UCP 2 - 5蛋白存在于多种组织中，但尽管与代谢紊乱、炎症、缺血性休克、癌症和衰老有关，但尚未得到很好的理解。本项目将利用我们在纯化和研究UCP 1分子性质方面的进展，重点确定UCP蛋白的核心性质，以了解结构功能关系及其生化作用。该研究将涵盖适用于膜蛋白的生物化学和分子生物学技术的广度（例如重组蛋白生产和纯化，色谱方法，脂质体重建/运输测定，诱变），包括研究膜蛋白配体结合和蛋白质-蛋白质相互作用的方法（例如蛋白质热稳定性变化分析，表面等离子体共振和流体流动诱导分散分析）。

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).