Cryptococcus neoformans is a pathogenic fungus responsible for serious infections in immunocompromised individuals. My lab studies aspects of cryptococcal biology that are of biochemical interest and may suggest targets for antifungal chemotherapy.
The main virulence factor of
C. neoformans is its extensive polysaccharide capsule, an elaborate and
…
more unusual structure that surrounds the cell wall and is required for fungal virulence. Our goal is to elucidate, at the molecular level, the biosynthesis and assembly of this unique capsule.
The processes that we are investigating include nucleotide sugar metabolism and transport, the enzymatic reactions required for capsule construction, secretion of capsular polysaccharides from the cell, and the association of the capsule with the cell surface. We are interested in the details of these reactions and what they teach us about glycobiology in general, as well as their specific roles in cryptococcal biology. The techniques we use to address these questions range from enzyme purification, transport assays, and imaging studies to exploitation of the newly available cryptococcal genome sequence for identification of genes of interest, forward genetics using an RNA interference library, and microarray analysis of gene expression. Through this combination of approaches we are progressing towards our goal of understanding capsule synthesis, and perhaps identifying ways in which to interfere with this process.
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