Microscopy of deformation processes in lipid bilayers

18. 在完成博士后工作后，我计划在研究型大学从事学术工作。在我的研究生工作中，我使用基于质谱的方法和分子建模模拟来了解极低介电介质（真空）中的肽构象。脂质膜在低介电介质（由脂质尾基提供）和水的高介电环境之间提供了独特的界面。我的博士后研究将为我提供三个核心领域的培训：脂质化学（包括囊泡和表面支撑脂质膜的制备），显微镜（光学和扫描探针）和纳米制造技术。我将在这些领域获得的知识和技能将使我能够制定一个研究计划，该计划采用多方面的方法来检查脂质和膜相关肽和蛋白质的相互作用。基于显微镜的技术提供了关于膜拓扑、材料性质和动力学的信息；质谱成像可以提供有关组成的补充信息（例如，鉴定翻译后的蛋白质修饰）。赞助商19。姓名与学位：Paul S. Weiss，博士职位/等级：化学教授扫描探针显微镜，分子电子学，表面分子自组装，膜生物物理学描述（请不要超过所提供的空间）这里描述的工作采用最先进的显微镜测量（光学和扫描探针）来检查脂质双层结构域的形成。特别关注的焦点是脂质结构对变形的反应。这项工作的三个具体目标包括：(1)微管支持解聚时囊泡的灾难性降解（这一过程与灵长类动物阿尔茨海默病的研究类似）；(2)脂液体积混合囊泡融合后三维成像方法；(3)表面支持脂质双层中蛋白-蛋白距离限制对结构域形成和细胞骨架生长模式的影响。小灵通416 - 1(牧师,12/98)表单页面2 BB cc的名字(最后,首先,初始)个人NRSA应用程序目录 ======================================== 节结束 ===========================================

18. GOALS FOR FELLOWSHIP TRAINING AND CAREER Following my postdoctoral work, I plan to pursue an academic career in a research university setting. In my graduate work, I used mass spectrometry-based methods and molecular modeling simulations to gain an understanding of peptide conformation in the ultimate low dielectric medium (vacuum). Lipid membranes provide a unique interface between a low dielectric medium (provided by the lipid tailgroups) and the high dielectric environment of water. My postdoctoral studies will provide me with training in three core areas: lipid chemistry (including preparation of vesicles and surface-supported lipid films), microscopy (optical and scanning probe), and nanofabrication techniques. The knowledge and skills I will gain in these areas will allow me to develop a research program that employs multifaceted approaches for examining the interactions of lipids and membrane-associated peptides and proteins. Microscopy-based techniques provide information about membrane topology, materials properties, and dynamics; mass spectrometric imaging can provide complementary information about composition (for instance, identifying post-translational protein modifications). SPONSOR 19. NAME AND DEGREE(S) Paul S. Weiss, Ph.D. 20. POSITION/RANK Professor of Chemistry 21. RESEARCHINTERESTS/AREAS scanning probe microscopy, molecular electronics, molecular self-assembly on surfaces, membrane biophysics RESEARCH PROPOSAL 22. DESCRIPTION (Do not exceed space provided) The work described here employs state-of-the-art microscopy measurements (optical and scanning probe) to examine domain formation in lipid bilayers. A particular focus of interest is in the response of lipid structure to deformation. Three specific targets of the work include: (1) catastrophic degradation of vesicles upon depolymerization of microtubule support (a process which has analogies in studies of Alzheimer's disease in primates); (2) lipid and fluid volume mixing in vesicle fusion followed by three-dimensional imaging methods; and (3) the effects of protein-protein distance constraints in surface-supported lipid bilayers on domain formation and cytoskeletal growth patterns. PHS 416-1 (Rev, 12/98) Form Page 2 BB cc NAME (Last,first, middle initial) Individual NRSA Application Table of Contents ========================================Section End===========================================