MSc by Research: The impact of gain-of-function mutations on Candida albicans antifungal drug tolerance and pathobiology

The MSc by Research programme at the University of Aberdeen is for students interested in a research-intensive master's degree. It is designed specifically to enhance your skills for a PhD or research career. You can find further information about our academic requirements and MSc by Research programme structurehere.

Candida albicans is a fungal pathogen that causes life-threatening infections, especially in immunocompromised patients. Currently there are only three main classes of antifungal drugs, and antifungal drug tolerance and resistance negatively impact on effective treatment of these infections. Mutation in drug targets can lead to drug resistance but the cellular mechanisms that lead to drug tolerance (the ability to grow slowly in the presence of normally inhibitory drug concentrations) remain poorly understood. Recently the Munro group completed the generation of a genome-wide library of overexpression mutants to improve C. albicans functional genomics through high throughput phenotyping. In this project we will utilise this new mutant collection to identify genes, that when overexpressed influence drug susceptibility, gaining a mechanistic understanding of the fungal response to antifungal agents. The focus primarily will be on cell signalling and cell wall related genes. Mutants identified to have altered drug tolerance will be characterised in more detail for changes in cell wall composition, biofilm formation and altered interactions with immune cells. Together this will generate knowledge of how gain-of-function mutations influence the drug susceptibility and pathobiology of C. albicans.

The key aim of this research project is to gain an understanding of the mechanisms that lead to antifungal drug tolerance in the major pathogen Candida albicans.

Specific aims:

1. Screen signalling and cell wall mutants from an overexpression library for altered echinocandin and azole drug tolerance phenotypes using growth assays.
2. Analyse drug tolerant mutants for changes in cell wall composition and biofilm formation.
3. Assess the phagocytosis of the drug tolerant mutants by murine macrophages in the presence and absence of antifungal drug treatment.

The student will receive extensive training in fungal cell growth, antifungal susceptibility and biofilm assays. They will gain in-depth experience in fluorescence and real time imaging microscopy, tissue culture and phagocytosis assays. They will learn to work independently and as part of a research team. Outside of the laboratory they will acquire skills in experimental planning and design, data recording, data and image analysis, data management, scientific writing and presentations.

Informal enquiries are encouraged, please contact Professor Carol Munro (c.a.munro@abdn.ac.uk) for further information.