Biophysical and biochemical studies of the mitochondrial uncoupling proteins

膜蛋白被并入细胞膜中和/或与细胞膜相互作用。 这些蛋白质负责维持生物体生命的各种生物学功能，例如跨细胞膜运输离子和营养物质以及通过促进电化学信号的传递在细胞之间进行通信。 在分子水平上了解这些功能的细节将显着提高对生命过程的洞察力，并有效地促进人类健康研究的几个领域。 线粒体解偶联蛋白（UCPs）是该研究计划的重点。这些有趣的蛋白质位于某些动物和植物组织的线粒体内膜中，并将呼吸与细胞中ATP的合成分开。关于膜中UCP的结构，只有有限的信息被记录下来。 除了这些蛋白质之一UCP 1在调节幼年哺乳动物体内温度方面的既定作用外，其他UCPs的详细生理作用尚不清楚。UCPs可能在氧化应激、脂质过氧化、糖尿病、发热、炎症过程和神经系统保护中发挥作用。因此，详细研究UCPs及其不同的和显然无关的生理作用是重要的，在理解某些细胞系统的分子生物学参与调节哺乳动物的重要生化过程。 拟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的折叠，以及作为其主要生物功能的离子转运机制的细节。 拟议的研究计划是原创的和跨学科的，并结合了合成，电生理，热化学和分子建模技术的结构分析的光谱方法在一个综合的研究，以探索解偶联蛋白质的结构与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.