The Coombs laboratory studies virus structure, function, assembly, and pathogenesis. They have been using mammalian reoviruses (MRV), avian reoviruses (ARV) and Influenza A viruses (IAV) as models for understanding how multiple proteins and nucleic acids recognize each other and interact to generate a functionally active macromolecular complex and how these complexes interact with host cells. They have generated and characterized sets of assembly-defective temperature-sensitive (ts) reovirus mutants. These mutants, as well as normal wild-type virus, are examined by biologic, molecular genetic, and mass spectrometric methods to better understand virus assembly and disassembly and the host proteomic response to virus infections. They also are conducting a variety of functional assays of viral RNA-dependent RNA polymerase, an enzyme unique to virtually all RNA viruses but absent from host cells, and analyzing compounds as potential anti-virals to aid development of therapeutic strategies to combat RNA viruses.