I am interested how the essential chaperone Hsp90 regulates yeast genetic and phenotypic diversity. Before becoming a Prize Fellow at the University of Bath, I trained as a postdoctoral fellow in the Cowen lab at the University of Toronto and studied for my PhD in the Dietrich lab at Duke University.
How do predominantly clonal fungi achieve phenotypic variation necessary for virulence?
Every year 700 people die in the UK of a disease called candidemia caused by the predominantly clonal yeast Candida albicans. Candidemia affects the weakest of the weak, such as low-birth weight infants and cancer chemotherapy patients. Unlike other pathogens, C. albicans can live asymptomatically in healthy people's mouths and GI tracts. Upon changes in the immune status, however, C. albicans turns pathogenic with mortality rates approaching 50%.
This transition from commensal to pathogen makes C. albicans highly unpredictable. Candidemia is difficult to treat due to the yeast's close assocation with humans and the lack of appropriate drug targets. The heat shock protein Hsp90 is instrumental in Candida virulence. We showed that Hsp90 regulates ~4% of the C. albicans genome by governing a genetic network that is environmentally contingent and has been largely rewired over the past 300-400 million years of evolution.
We employ gemomic and proteomic tools as well as standard yeast molecular biological techniques to understand how Hsp90 regulates fungal virulence through its interaction network and through specific kinase interactors. Specifically, we are interested in understanding:
How does the Hsp90 chaperone network change over evolutionary time and what are the consequences for environmental adaptation?
How does kinase-mediated regulation of the Hsp90 complex affect fungal stress response pathways and virulence?
How does Hsp90 regulate genome integrity in C. albicans?