The work in my laboratory focuses on structural analysis of the complex cell-entry machinery of herpesviruses with the ambition to develop a "molecular movie" illustrating successive steps during entry. Herpesviruses are a family of human pathogens, such as Herpes Simplex virus, cytomegalovirus, and Epstein-Barr virus, that infect their hosts for life, causing cold sores, blindness, encephalitis, cancers, and life threatening conditions in immunocompromised individuals. While most enveloped viruses use a single viral protein to effect cell entry, all herpesviruses require at least three conserved proteins: gB, gH, gL Some herpesviruses also require an additional receptor-binding protein. We are interested in determining how gB and gH/gL work together to accomplish membrane fusion - a process at the core of viral entry - and how the signal from the receptor-binding protein triggers the membrane-fusion apparatus. Our approach combines using x-ray crystallography to determine the structures of individual proteins with other biophysical and biochemical techniques to study their interactions. Knowing the detailed mechanisms of herpesvirus entry into cells may lead to the design of antiviral therapeutics. From a broader biological perspective, understanding how and why herpesviruses use several proteins to accomplish membrane fusion will increase our understanding of membrane fusion in general.