The roots of our research program are in the power of x-ray crystallography to reveal the structures of membrane-interacting proteins at high resolution, leading to insights in the physical basis of protein-membrane interactions. Crystallography continues to be at the heart of our research because of its unequaled power to reveal the shape of proteins and the atomic basis for protein-protein and protein-lipid interactions. The reconstitution of membrane remodeling pathways in synthetic membrane systems has recently taken on equal importance in the lab. Both the crystallographic and membrane reconstitution programs in the lab are driven by our ability to generate intact, biochemically functional multiprotein complexes using expression systems that include E. coli, yeast, insect cells, and mammalian cell culture.  Membrane remodeling is reconstituted in the lab in giant unilamellar vesicles, a method that allows visualization of membrane structural changes by fluorescence microscopy. These core approaches are complemented by lower resolution studies in solution or on membranes by hydrodynamic, small angle x-ray scattering, and site-specific fluorescent labeling approaches within the lab, and through collaborative electron microscopy. The presence of the membrane has a profound effect on the nature of protein-protein interactions, and a variety of fluorescence-based approaches are being pursued to study these interactions in their native membranous environment. Biological hypotheses generated from structural and in vitro analyses are tested in vivo whenever possible. In our lab we use yeast as a model system, and function in human cells is tested in collaboration with other laboratories in the outstanding cell biology and virology communities at NIH.