The yeast sterol pathway and its end-product, ergosterol, remain the major targets for antifungal therapy. Our goal is to understand how sterol synthesis is regulated and to assess which steps in the sterol biosynthetic pathway are absolutely necessary for yeast viability. We have cloned nine ergosterol biosynthetic genes and gene disruption studies surprisingly indicate that only four are essential for cell viability. Our present studies include determining the nature of protein-protein interactions among sterol biosynthetic enzymes and the possibility of a sterol biosynthetic channeled complex. Our long-term goals are to understand the nature of sterol trafficking in which sterols are transported from their site of synthesis to various intracellular membranes as well as to determine whether sterols have cellular functions other than as bulk membrane sterol components. Our investigations also have implications in medicine as a number of different genetic syndromes have been identified in which cholesterol synthesis is defective.
Department of Biology