Project No.2204
Primary Supervisor
Dr Alessia Buscaino – University of Kent
Co-Supervisor(s)
Prof Georgios Giamas – University of Sussex
Summary
The emergence of drug-resistant pathogens is an increasing problem as it diminishes our ability to treat common infections
Especially alarming is the global spread of antifungal drug resistance occurring when fungal pathogens no longer respond to drugs. Fungal pathogens are a threat to animal, plant and ecosystem health. Indeed, fungal diseases cause ~ 1.5 million human death annually. Pathogenic fungi are also a worldwide threat to food security, as they can infect plants and crops, and fungal infections are driving the extinction of several animal groups, including bats, amphibians and reptiles.
This project aims to understand the mechanisms of antifungal drug resistance in Candida albicans, the most common human fungal pathogen. C. albicans commonly live in the human body without causing any harm. However, C. albicans can cause life-threatening infections in immunocompromised individuals such as cancer patients undergoing chemotherapy treatments. There are only three types of effective antifungal drugs to treat C. albicans infection, and the emergence of drug resistance severely hinders our therapeutic options.
Proteins are the primary functional molecules in all living organisms, including fungal pathogens. Proteins can be chemically modified in a process known as Post-Translation Modification (PTM). PTMs modulate the function, localisation and activity of proteins. The Buscaino lab has recently identified SUMOylation as a key PTM regulating C. albicans antifungal drug resistance. Indeed, C. albicans strains lacking key SUMO enzymes develop resistance to antifungal drugs by accumulating specific genomic rearrangements. This PhD project combines our expertise in fungal genetics, genomics (Buscaino), quantitative proteomics and bioinformatics (Giamas) to unveil how and why C. albicans protein SUMOylation leads to drug resistance and how the SUMOylation machinery regulates the C. albicans proteome in response to antifungal drugs