Diversity in the Regulatory Landscape Governing Candida albicans Biofilm Formation

The diploid dimorphic fungus Candida albicans displays a remarkable degree of phenotypic diversity among members of the species. In particular, strains display significant variability in capacity for filamentation and biofilm formation, virulence determinants of this clinically relevant human pathogen. Phenotypic diversity has not thus far been investigated in our studies of C. albicans virulence determinants, primarily because genetic engineering in this species relies on a single laboratory strain lineage:
SC5314 and its engineered derivatives. In this dissertation, we discuss several methods to rapidly investigate gene function in multiple clinical isolates, and use both Nanostring
and RNA-seq to compare regulatory circuitry governing filamentation and biofilm formation in C. albicans. We identify widespread circuit diversification, a phenomenon where a target gene is under the control of regulator A in background A, yet under the control of regulator B in background B. Finally, we explore possible mechanisms that
may underlie circuit diversification, and investigate multi-strain core targets for gene function in filamentation.