DSSS - Harnessing diversity to understand eukaryotic mechanisms of stress response

Fungal infections cause millions of deaths each year and are difficult to treat because most biochemical and cellular processes are conserved between fungi and humans. Candida albicans is a human commensal and opportunistic pathogen, and a prevalent cause of both mucosal and life-threatening fungal infections. Bona fide resistance to the small arsenal of antifungal drugs is relatively rare, but tolerance to those drugs is much more prevalent. We define antifungal drug tolerance as the ability of some cells in the population to grow slowly in the presence of drug concentrations that arrest the growth of other cells in the same isogenic population. Tolerance involves phenotypic heterogeneity in which some cells grow, and others don’t; this heterogeneity is heritable, implying that cell-to-cell differences reflect metabolic rather than genetic changes. Furthermore, different isolates have different levels of tolerance, which we assume are due to differences in genetic background between them. I will discuss our work (done together with the Ralser lab) to collect 1700 C. albicans isolates, and to use genomics, phenomics and proteomics to improve our understanding of the metabolic, cellular and genetic processes that can explain the breadth of phenotypic diversity within the C. albicans species.