RESEARCH: Our laboratory studies the interactions that occur between invading microbes and their target host cells which result in the induction of pathological consequences, or disease. We approach the study of microbial pathogenesis using two different model systems, on viral and the other bacterial. Our virology model is the mammalian poxvirus, vaccinia virus (VV). We are using molecular biological approaches to dissect the VV replicative cycle. In particular we are examining the role that posttranslational modifications such as acylation and proteolysis play in determining how viral proteins acquire functional integrity and become localized to the proper intracellular location in order to carry out their intended activity. Our bacterial model is the gram-positive bacteria, in particular the Group A streptococci. We are studying the pathways by which bacterial virulence factors, such as adhesins, become exported and anchored to the cell surface. Both projects share a common theme of basic research into a particular aspect of the host-pathogen relationship, followed by application of the derived knowledge to design prophylactic or therapeutic intervention strategies. Towards this goal, we are developing several recombinant vaccines and anti-infectives for potential use in humans. In recent years, we have focused on issues of biowarfare defense. To that end, we have developed a safer smallpox vaccine and two candidate smallpox antiviral drugs, all of which are about to enter animal testing en route towards clinical and regulatory approval.