Office: Thompson Biology Lab 218
Phone: (413) 597-2196
E-mail: nancy.roseman@williams.edu
Area of Interest: Virology
My research is focused on an enzyme involved in DNA metabolism, deoxyuridine triphosphatase (dUTPase). This enzyme has been shown to be essential in a variety of prokaryotic and eukaryotic organisms. To study the enzyme my lab utilizes vaccinia virus, a eukaryotic animal virus, as a model system. Vaccinia is unique in that it replicates solely in the cytoplasm of host cells: this requires the virus to encode the metabolic machinery necessary for DNA replication. Vaccinia is relatively easy to manipulate genetically, so mutants in dUTPase can be engineered and enzyme activity assayed in vivo. As the host encoded its own dUTPase, following the enzyme is also an excellent way to study the effect of viral infection on basic functions of the host.
Structure/function studies of the enzyme are proceeding using a bacterial expression system to generate large amounts of the viral enzyme. Mutants generated by directed genetics will be assayed for native structure and enzymatic characteristics. To facilitate this project we are collaborating with Professor Robert Evans of the Williams Chemistry department. His lab provides azido nucleotide analogs that are used in cross-linking experiments to define regions of the protein necessary for catalysis.