My laboratory is interested in developing tools to study the biosynthesis of bacterial exopolysaccharides and the role of these exopolysaccharides in biofilm formation and bacterial infections. Projects in the lab use a multidisplinary approach combining synthetic carbohydrate chemistry, enzymology, membrane protein biophysics and molecular biology to study the structure, biosynthesis, membrane transport, and functions of exopolysaccharide that make up the extracellular matrix of bacterial biofilm communities.
A second area of study in my lab focuses on the activity of bifunctional glycosyltransferase (GT) enzymes. Unlike protein and nucleic acid biosynthesis, which use a template strand to control polymer sequence and length, the biosynthesis of polysaccharides is template independent. As a result, polysaccharide biosynthesis often requires multiple GT enzymes, each specific for adding a single monosaccharide to the growing polymer. However, there are a number of polysaccharides that contain a disaccharide repeat unit that are assembled by single bifunctional GT enzymes. Projects in the lab aim to understand how bifunctional GT are able to control polymer sequence and chain length during polysaccharide biosynthesis.
My lab also seeks to develop chemical probes that disrupt exopolysaccharide biosynthesis in order to study their role in biofilm assembly in vivo. We combine mechanism based inhibitor design and transition state analog design approaches based on KIE measurements to develop inhibitors of the glycosyltransferase enzymes involved in exopolysaccharide biosynthesis.