Microscopy of deformation processes in lipid bilayers

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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===========================================