Epigenetic mechanisms mediating antifungal resistance

Fungal survival in harsh environments involves stress-sensing pathways that reprogram their proteomes. New conditions, including global heating, can push opportunistic fungi to colonise novel niches, potentially becoming harmful pathogens. Effective antifungal treatments are limited in number precisely because fungi are adept at resisting challenges. We discovered that external insults cause fission yeast to form repressive heterochromatin over various genes whose reduced expression confers resistance (e.g. mitochondrial proteins). By combining genetic, genomic, transcriptomic, proteomic, metabolomic, bioinformatic and mathematical analyses we will provide a comprehensive understanding of the regulatory mechanisms utilized by cells that successfully acquire resistance. We will determine whether conserved or divergent epigenetic mechanisms underlie antifungal resistance in: (i) Cryptococcus neoformans, which infects immunocompromised patients, (ii) the wheat pathogen Zymoseptoria tritici, an exemplar of fungal pathogens threatening global cereal supply, food security and human wellbeing. We expect these discoveries will ultimately aid design of more astute and specific antifungal agents.