Annually, fungal diseases cause approximately 1.6 million deaths and are responsible for the failure of crops that would feed 300 million people. In spite of this, there are very few treatment options to fight fungal pathogens, and furthermore, the rise in antifungal resistance puts into question the continued effectiveness of our current arsenal of drugs.
Being eukaryotes, fungi package their genome as chromatin into the cell’s nucleus, and histone posttranslational modifications (PTMs) dynamically change chromatin organization in response to the physiological needs of the fungus. We have shown that by inhibiting histone PTM pathways in the pathogenic yeast, Candida glabrata, we render it more sensitive to common antifungals, suggesting a novel treatment option. The goal of this project is to assess the universality of these findings and evaluate the viability of this approach to tackle fungal infections.
Working with collaborators in Belfast city hospitals, other clinically relevant Candida species will be treated with “epigenetic probes” that target specific histone PTM pathways. The effect of these probes on fungal viability, fungal virulence and anti-fungal resistance will be determined. Combinations of drug(s) and species that show an anti-fungal effect, will be mechanistically dissected by interrogating both the fungal transcriptome and chromatin landscape.
Specific skills/experience required by applicants:
Applicants should have training in microbiological aseptic technique.
Only UK and EU students are eligible to apply. Information on eligibility criteria is available from DfE: View Website