The Smith lab is primarily focused on understanding the role of defensins in viral pathogenesis and evolution. Defensins are a class of antimicrobial peptides with broad antibacterial, antiviral, and antifungal activity. Their effects on viral infection, immunity, pathogenesis, and evolution, particularly for nonenveloped viruses, are incompletely understood. Using a variety of approaches from virology, cell biology, biochemistry, structural biology, and genetics, our work is focused on understanding the interaction of defensins with non-enveloped viruses in molecular detail to determine general principals of defensin-mediated neutralization of viral infection. We are also interested in using animal models of enteric viral diseases to understand the role of defensins in antiviral immunity in vivo. Finally, we use 3D intestinal enteroid culture methodology to examine the interaction of viruses and bacteria with host cells and to study the cell biology of epithelial cell types that were previously unculturable.