The overall objective of our research is to understand how protein interactions determine subcellular structure. We use direct structural approaches -- principally X-ray crystallography -- to determine the atomic organization of macromolecular complexes. Our present work tackles three groups of questions about molecular localization in cells: (1) how do viruses assemble and get into and out of cells? (2) how do protein assemblies that control transcription integrate diverse signals in switching on or off the expression of specific genes? (3) what is the nature of the molecular machinery for various transport steps in membrane traffic? Specific projects related to cancer include studies of human papillomavirus 16 (HPV16), polyomaviruses, Src and Pak kinases, NFkB, IkB and NFAT. Our Howard Hughes Medical Institutes laboratory is integrated with that of Don Wiley, at tow locations -- the Fairchild Building in the Harvard Department of Molecular and Cellular Biology and the Enders Building at Boston Children's Hospital.