How does the pathogen Candida albicans sense heat and activate the thermal adaptation mechanisms that promote infection?. (360G-Wellcome-096072_Z_11_Z)

The major fungal pathogen of humans, Candida albicans, is frequently exposed to temperature changes in host niches. This pathogen must sense and adapt to these thermal fluctuations to establish infections. Therefore, my first goal is to determine how C. albicans cells sense changes in ambient temperature by defining the thermal sensor. In parallel, my second goal is to characterise the biological thermostat i.e. the mechanism(s) by which cells fine-tune the degree of thermal adaptation to the thermal fluctuation. I recently showed that key signalling pathways contribute to thermal adaptation in C. albicans: i.e. the Mkc1, Hog1 and Cek1 pathways. Therefore, my third goal is to establish how these pathways contribute to thermotolerance, in part through modulation of global gene expression patterns. These mechanisms are likely to be conserved in other eukaryotic systems. Therefore, my fourth goal is to test whether other pathogenic fungi such as Cryptococcus neoformans (which occup ies diverse niches in the environment as well as in humans), sense temperature through analogous mechanisms. My fifth goal is to determine how specific thermal adaptation pathways contribute to fungal virulence. By addressing these goals this project will dramatically advance our understanding of eukaryotic thermal adaptation mechanisms.