Lipid Asymmetry: A New View on Lipid Dynamics and Membrane Structure

脂质不对称：脂质动力学和膜结构的新观点

• 批准号: 1110351
• 负责人: John Conboy
• 金额: $ 46.5万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1110351&HistoricalAwards=false
• 关键词: Lipid; Asymmetry; New; View; Dynamics

The Chemistry of Life Processes Program supports Professor John C. Conboy at the University of Utah whose research will explore and understand the complex interplay between the movement of lipid species across the cellular membrane and the establishment of lipid compositional asymmetry. The connection between lipid compositional asymmetry and flip-flop in planar supported lipid bilayers will be explored using a novel application of sum-frequency vibrational spectroscopy (SFVS) developed by the PI to selectively probe the asymmetry in a planar-supported lipid bilayer (PSLB). This new surface analytical method allows for the direct detection of lipid flip-flop without the need for a fluorescent or spin-labeled lipid probe, which can alter the measured translocation rates. The goal of this research is to use this surface analytical tool to address some of the central issues concerning the transbilayer movement and the establishment of lipid asymmetry in bilayer systems. In addition, the coupling of lipid flip-flop energetics to the establishment of lipid asymmetry will also be explored. These studies are aimed at providing physical insight into the mechanism of lipid compositional asymmetry.With the support of the Chemistry of Life Processes Program in the Chemistry Division at the National Science Foundation, Professor Conboy will perform research that has far-reaching implications in molecular and cellular biology and will provide a foundation for interpreting the influence of small molecules such as cholesterol and the influence of transmembrane peptides on lipid flip-flop and distributions in living cells. In addition to the studies outlined above, which will provide a solid foundation for the investigation of transbilayer movement of phospholipids across the membrane, studies could be extended to examine the exchange of fatty acids, steroids, hormones and other small molecules, all of which dramatically modulate the physical properties of lipid membrane. The goal of the education plan is to incorporate the concepts of bioanalytical chemistry into the graduate and undergraduate analytical curriculum. At the graduate level, the continued enhancement of the core analytical curriculum will be achieved by the offering of bioanalytical chemistry, a course that the PI has developed. The course is designed to utilize the most recent analytical techniques used in the biological sciences and draws heavily from the literature, exposing students to the latest advancements in the field. At the undergraduate level, the introduction of bioanalytical principles and techniques in the undergraduate instrumental analysis laboratory will be introduced. This will not only give students exposure to bioanalytical techniques, but will also entail the use of problem-solving based exercises. Several undergraduates will be involved in ongoing research in the laboratory of Professor Conboy, in order to foster a growing interest in biophysical/bioanalytical chemistry.

生命过程计划的化学支持教授约翰C。犹他州大学的Conboy博士说，他的研究将探索和理解脂质物质穿过细胞膜的运动和脂质成分不对称性的建立之间复杂的相互作用。脂质组成的不对称性和触发器之间的连接在平面支持的脂质双层将探索使用和频振动光谱（SFVS）的PI开发的一种新的应用程序，选择性地探测平面支持的脂质双层（PSLB）的不对称性。这种新的表面分析方法允许直接检测脂质触发器，而不需要荧光或自旋标记的脂质探针，这可能会改变测量的易位率。本研究的目标是使用这种表面分析工具来解决一些关于跨双层运动和建立双层系统中的脂质不对称性的核心问题。此外，还将探讨脂质翻转能量学与脂质不对称性建立的耦合。这些研究旨在为脂质组成不对称性的机制提供物理见解。在美国国家科学基金会化学部生命过程化学计划的支持下，康博伊教授将进行一项研究，这项研究已经远远-达到分子和细胞生物学的影响，并将提供一个基础，解释小分子的影响，如胆固醇和跨膜的影响，肽对脂质翻转和在活细胞中的分布的影响。除了上面概述的研究，这将提供一个坚实的基础，磷脂跨膜的transbilayer运动的调查，研究可以扩展到检查交换的脂肪酸，类固醇，激素和其他小分子，所有这些都显着调节脂质膜的物理性质。教育计划的目标是将生物分析化学的概念纳入研究生和本科生的分析课程。在研究生阶段，核心分析课程的持续加强将通过提供生物分析化学来实现，这是PI开发的一门课程。该课程旨在利用生物科学中使用的最新分析技术，并大量引用文献，使学生了解该领域的最新进展。在本科阶段，将介绍本科仪器分析实验室的生物分析原理和技术。这不仅会让学生接触到生物分析技术，而且还需要使用基于解决问题的练习。几个本科生将参与正在进行的研究在Conboy教授的实验室，以促进生物物理/生物分析化学的兴趣日益增长。