From Tolerance to Resistance: Understanding Antifugnal Survival Mechanisms in Fungal Pathogens
Supervisors
Dr Edel Hyland, Queens University Belfast
Dr Arne Jacobs, University of Glasgow
Summary
Fungal infections are an urgent global threat, causing >3.5 million deaths annually and rising as antifungal resistance spreads. A key challenge is antifungal drug tolerance (ADFT), a reversible phenotypic state where a subset of fungal cells survives drug levels far above the mimimal inhibitory concentration (MIC), often preceding permanent genetic resistance. This project targets pathogenic yeasts Nakaseomyces glabratus and multidrug-resistant Candida auris to decode the biology underlying ADFT.
Aims
1. Explore if population-level heterogeneity drives ADFT using fluorescent reporters and flow cytometry across environmental, pharmacological, and genetic conditions.
2. Identify genetic determinants shaping this heterogeneity through genome sequencing and genotype-phenotype mapping.
3. Test whether tolerant cells accelerate resistance by isolating them and tracking
experimental evolution under antifungal pressure.
This work will uncover the mechanisms of ADFT, revealing strategies to combat persistent, drugrefractory fungal infections. The PhD provides hands-on training in cutting-edge molecular microbiology, genome editing, fluorescent reporter assays, and flow cytometry, paired with bioinformatics and experimental evolution. Students will also develop transferable skills in scientific communication, project management, and interdisciplinary collaboration, equipping them to tackle fungal resistance challenges and pursue careers in academia, biotech, or healthcare.