Project Summary/Abstract Candida albicans is one of the most prevalent fungal pathogen of humans and also a component of the human microbiome; it can cause superficial infections in normal humans and life-threatening systemic infections in immune compromised individuals. Our work seeks to understand how C. albicans regulates its genes so it can survive and proliferate in the many different environments of its human host. This proposal focuses on a single, large transcription circuit—the white-opaque switching circuit—which allows two different cell-types to be produced epigenetically from the same genome. White-opaque switching is deeply conserved across clinical isolates of C. albicans and is also observed in closely related Candida species. This proposal seeks to understand the mechanism behind white-opaque switching, the mechanisms underlying the stability of the two distinct, epigenetic cell-types and the effects of white-opaque switching on Candida’s ability to thrive in its mammalian hosts.