Biophysical and biochemical studies of the mitochondrial uncoupling proteins

膜蛋白被结合到细胞膜中和/或与细胞膜相互作用。这些蛋白负责多种生物功能，如跨细胞膜的离子和营养物质的运输，以及通过促进电化学信号的传递来促进细胞之间的通信。在分子水平上了解这些功能的细节将显著提高对生命过程的洞察，并有效地为人类健康研究的几个领域做出贡献。线粒体解偶联蛋白(UCPs)是本研究计划的重点。这些耐人寻味的蛋白质位于某些动植物组织线粒体的内膜中，将呼吸与细胞中的ATP合成解偶联。关于膜上UCPs的结构，只有有限的信息被记录下来。除了这些蛋白质之一UCP1在调节幼年哺乳动物体内温度方面的既定作用外，其他UCPs的详细生理作用还不清楚。UCPs在氧化应激、脂质过氧化、糖尿病、发热、炎症过程和神经系统保护中的可能作用已被提出。因此，对解偶联蛋白及其不同的、明显无关的生理作用的详细研究，对于了解参与哺乳动物重要生化过程调控的某些细胞系统的分子生物学具有重要意义。建议的研究计划将侧重于探索解偶联蛋白的膜结构，它们与膜的相互作用和在膜中折叠，以及作为其主要生物学功能的离子传输机制的细节。建议的研究计划是原创性的和跨学科的，并将结构分析的光谱方法与合成、电生理、热化学和分子建模技术相结合，在综合研究中探索解偶联蛋白结构-功能关系的生物物理基础。

Membrane proteins are incorporated in and/or interact with the cell membranes.  These proteins are responsible for a variety of biological functions crucial for the maintenance of life in living organisms, such as transport of ions and nutrients across cell membranes and communication in between cells through facilitating the transfer of electrochemical signals.  Understanding the details of these functions at the molecular level will significantly improve the insight into the life processes and effectively contribute to several areas of human health research.  Mitochondrial uncoupling proteins (UCPs) are the focus of this research program. These intriguing proteins are located in the inner membranes of the mitochondria of certain animal and plant tissues, and uncouple the respiration from the ATP synthesis in cells. Only limited information has been documented on the structures of UCPs in membranes.  Apart from the well-established role of one of these proteins, UCP1, in regulating the temperature in the body of young mammals, the detailed physiological roles of other UCPs are not clearly understood. Possible roles of UCPs in response to oxidative stress, lipid peroxidation, diabetes, fever, inflammatory processes and nervous system protection have been suggested. Consequently, detailed studies of UCPs and their diverse and apparently unrelated physiological roles is significant in understanding the molecular biology of certain cellular systems that are involved in regulation of vital biochemical processes in mammals.   The proposed research program will focus on exploring the membrane structure of the uncoupling proteins, their interaction with and folding in membranes, and the details of the ion transport mechanism as their major biological function.  The proposed research program is original and interdisciplinary, and combines spectroscopic methods of structural analysis with synthetic, electrophysiological, thermochemical and molecular modeling techniques in an integrated study to explore the biophysical basis of the structure-function relationships in the uncoupling proteins.