The budding yeast S. cerevisiae is a model organism in which the power of genetic screening and genomic analysis can be combined with biochemical reconstitution approaches to dissect complex cell biological mechanisms that are conserved in humans. Historically, my lab has been using budding yeast to study several mechanisms ranging from selective autophagy, targeting and insertion of membrane proteins to organelles, and transcriptional control of protein folding in the cell. More recently, we have been carrying out genome-wide mammalian cell screens using CRISPR/Cas9 technologies to uncover novel regulatory components with direct connections to human autophagy diseases.