Targeting yeast epigenetics to combat anti-fungal resistance

Project details:

One consequence of climate change is the increased incidence of fungal disease, as global temperatures become more aligned with optimal fungal growth conditions. The very limited current arsenal of antifungal drugs, together with the increasing prevalence of antifungal drug resistance, puts into question our continued ability to fight fungal disease, therefore threatening human health and global food security.

We have identified a novel therapeutic pathway to treat fungal infections caused by the yeast species Candida glabrata. We have shown that removal of the histone deacetylase gene, cgRPD3, not only reverses anti-fungal resistance in this species, rendering it more susceptible to common antifungals, but also attenuates in vivo virulence of this increasingly prevalent human pathogen.

We are interested in designing a yeast specific small molecule inhibitor of the cgRpd3p protein as a potential antifungal drug. Towards this end, this PhD project will focus on the purification and crystallization of recombinant cgRpd3p to obtain structural information on this protein. Informed by these structural studies, site specific cgRPD3 mutants will be engineered and their in vivo phenotypic effects on fungal virulence and anti-fungal drug resistance investigated. This will identify key residues in cgRpd3p that may be suitable targets for protein inhibition.

This project will be supervised by Dr Edel Hyland and Dr Chris Law of Queen’s University School of Biological Sciences.

All applications MUST be submitted through https://dap.qub.ac.uk/portal/user/u_login.php.

Specific skills/experience required by applicants:

A background in protein structure and function.

All applicants must meet the academic entry requirements: https://www.qub.ac.uk/courses/postgraduate-research/biological-sciences-phd.html#entry