Research in our lab is directed towards understanding basic mechanisms of intracellular protein targeting. We use the yeast Saccharomyces cerevisiae which allows for a combined genetic and biochemical approach. Currently, we are pursuing three major areas of interest. One project focuses on understanding the molecular mechanism of quality control at the endoplasmic reticulum (ER): only properly folded proteins of the secretory pathway are allowed to advance to the cell surface while proteins which fail to fold properly are targeted for ER-associated degradation by cytosolic proteasomes. We are interested in understanding how a protein in the process of folding normally is distinguished from a misfolded one. A second major project is centered on protein sorting in distal secretory and endocytic pathways. Evidence is accumulating in support of a post-ER quality control mechanism that recognizes and targets defective proteins to the endosomal/vacuolar pathway for degradation. A third major project addresses the role of lipid rafts in maintaining protein stability upon arrival at the plasma membrane. We are studying the inter-relationships of protein phosphorylation, ubiquitination, and lipid raft association. In addition to playing a crucial role in cell compartmentation, these processes are all implicated in human health, as a wide range of diseases are associated with defects in protein trafficking in the secretory pathway, including cystic fibrosis and familial hypercholesterolaemia.