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• genetics, genomics and molecular biology
• infectious disease and the immune system

• Medicine

• Infectious diseases

My lab is interested in determining factors controlling virulence in pathogenic fungi, particularly Candida species. We have various projects, for example identifying the regulatory pathways controlling the growth of biofilms of Candida parapsilosis on medical devices; investigating the response of pathogenic Candida to hypoxia; and characterising the role of specific yeast transcription factors in virulence. In more recent work we are using Next Generation Sequencing to investigate variation in clinical and environmental isolates of Candida.

Wu et al. Genus-Wide Comparative Genomics of Malassezia Delineates Its Phylogeny, Physiology, and Niche Adaptation on Human Skin. PLoS Genet. 2015 Nov 5;11(11):e1005614.
Holland et al. Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicans. PLoS Pathog. 2014 Sep 18;10(9):e1004365.

Candida species are the leading cause of opportunistic mycoses and a common cause of nosocomial bloodstream infections. Much remains unknown about the origins and virulence mechanisms of these fungal pathogens. Most studies have concentrated on detailed analyses of single isolates. However, recent work using multiple isolates from single species has illustrated the association of particular clades with specific virulence-associated phenotypes. For example, it has been shown that resistance to the antifungal drug flucytosine is predominantly found within clade I of C. albicans, due to a mutation in the FUR1 gene. In this study, we will use whole genome sequencing to sequence and analyse several Candida isolates from environmental and clinical sources. We will then assess the correlation between genetic subgroup and phenotypic profile, through use of in vitro and in vivo virulence assays.

The majority of clinical isolates will be obtained from a collaboration with Prof. Tom Rogers at St James?s Hospital, Dublin and from Centers for Disease Control in the US. Environmental isolates will be collected locally, and in collaboration with Dr Chris Hittinger at the University of Wisconsin-Madison. Whole genome sequencing of approximately 96 isolates will be carried out using NextSeq Illumina technology, either on-site in UCD or using commercial companies. Virulence will be assayed using the larvae of the moth Galleria mellonella, and using human epithelial cell lines, including TR146 (oral epithelial cell line) and HMV-II (vaginal epithelial cell line). Genotypic characteristics will also be correlated with other phenotypic characteristics, such as resistance to antifungal drugs. It may be possible to extend the project to characterise the response of the host and pathogen to infection, using RNA-seq.