Associate Research Fellow
Geoffrey Pope 309
Geoffrey Pope Building, University of Exeter , Stocker Road, Exeter, EX4 4QD, UK
PhD Biological Sciences, University of Exeter
BSc (hons) Microbiology, Imperial College London
Characterisation of stress resistance mechanisms in the pathogenic yeast Candida glabrata
During infection, pathogenic microorganisms encounter and must overcome a variety of stresses in the host environment. My research focuses on understanding how the pathogenic yeast Candida glabrata survives oxidative and osmotic stresses, both singly and in combination. The generation and sequencing of stress-resistant C. glabrata mutants will facilitate our understanding of such mechanisms through the identification of novel mutations conferring stress resistant phenotypes.
Candida glabrata is a significant and increasingly common pathogen of humans yet its mechanism of virulence remains unclear. Comparative genomic studies revealed that C. glabrata is more closely related to the non-pathogenic yeast Saccharomyces cerevisiae and that both these genomes are distinct from C. albicans. In order to explore C. glabrata virulence attributes, C. glabrata ORFs with no orthologue in S. cerevisiae were studied since these ORFs may have accompanied the adaptation of C. glabrata to the human host.
Reciprocal best hit searches identified C. glabrata ORFs with no S. cerevisiae orthologue. A barcoded deletion library targeting 65 C. glabrata-specific ORFswas constructed. To functionally characterise the deletion library, mutants were tested for fitness and phenotypically screened to identify gene products required for growth in response to biologically relevant stresses. As such, novel phenotypes associated with the deletion of previously uncharacterised ORFs were uncovered. Mutants were also tested for infection-related properties including biofilm formation, antifungal agent susceptibility for virulence in a Drosophila melanogaster infection model, resulting in the identification of two ORFswhich were required for virulence.
An adapted genome-wide synthetic genetic interaction approach was used to create genetic interaction networks for C. glabrata ORFs over-expressed in S. cerevisiae. Genetic interaction analysis of a C. glabrata HMG-box chromatin remodeler revealed a putative role for this ORF in DNA damage repair.
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