My research interests are focussed on understanding the pathogenicity of the most common life-threatening fungal agent Candida albicans in order to design better therapies to combat invasive fungal infections. I am particularly interested in the fungal wall as it is central to pathogen-host interactions and is an attractive target for novel therapies. We are studying how the cell surface is remodelled in response to the environment including exposure to antifungal drugs and growth in vivo and the signalling pathways that govern cell wall remodelling. We study the signalling pathways that regulate cell wall synthesis and re-modelling, and their target genes, especially cell surface proteins that have potential roles in pathogenesis including interactions with the host. My research team are investigating the function and transcriptional regulation of a subset of novel GPI-anchored proteins. We are also using a LC-MS/MS approach to study the complement of cell wall proteins in a range of C. albicans cell wall and signalling mutants and in response to antifungal drugs. In collaborative projects with Prof Neil Gow we are investigating the molecular mechanisms that regulate fungal chitin biosynthesis and how activation of cell wall salvage pathways results in increased cell wall chitin, which leads to reduced susceptibility to the echinocandin antifungal drugs in vitro and in vivo. I am also involved in comparative genomic projects analysing cell wall genes in a number of fungal species.
My research also spans antifungal drug development and I have been awarded a Knowledge Transfer Partnership grant, SULSA Bioskape industrial studentship and a MRC CASE studentship with NovaBiotics Ltd to develop antimicrobial peptides as therapies for systemic fungal and polymicrobial infections. I have initiated an antifungal drug discovery programmes through internal Commercialisation Awards and have screened the natural compound library of the Marine Discovery Centre, based at Aberdeen. I was granted SULSA funding for a targeted antifungal drug screening programme with the University of Dundee Drug Discovery Unit and to develop antibodies against fungal cell surface proteins with the Scottish Biologics Facility with the long term plan of testing their utility as biomarkers of invasive fungal infections and/or therapeutics.
A further area of research is functional genomics and through a Wellcome Trust Biomedical Resources grant jointly funded with Dr Christophe D’Enfert, Institut Pasteur my group are constructing C. albicans ORFeome and over-expression libraries that will be distributed to the community. My aim is to use the over-expression collection to perform high throughput phenotypic analysis to gain a better understanding of fungal virulence and to improve the existing genome annotation by elucidating the roles of uncharacterised genes.
I am a partner in the EU -funded Innovative Training Network OPATHY (From Omics to Patient: Improving Diagnostics of Pathogenic Yeasts) http://www.opathy.eu/ Within this network we are developing antifungal drug resistance biomarkers using a proteomics approach.
Dr Mathias Richard, INRA, Grignon, France – Functional analysis of C. albicans GPI-proteins.
Dr Kevin Verstrepen, Katholieke University, Leuven, Belgium – Genome-wide tandem repeat analysis of Candida spp.
Dr Piet de Groot, University of Amsterdam, The Netherlands - Cell wall proteomics.
Dr Christophe D'Enfert Pasteur Institute, France, - C. albicans ORFeome and over-expression library.
MRC Case studentship with NovaBiotics Ltd 2013-2017 Novel combination strategies to combat complex respiratory polymicrobial infections associated with cystic fibrosis.
Wellcome Trust Strategic Award Cross-disciplinary PDRA Project Award 2013-2017 (co-PI with Prof Ramage, University of Glasgow) Evaluating clinical outcomes to Candida albicans biofilm formation in candidaemia patients.
Wellcome Trust Strategic Award International PhD Scholarship 2014-2017 (co-PI with Dr Campbell Gourlay, University of Kent) Investigating the role of mitochondrial electron transport chain function in fungal pathogenicity and drug resistance.
EU OPATHY Innovative Training Network 2015-2018 fungal diagnostics.
Wellcome Trust ISSF award 2016-2017 barcode sequencing.
MRC Confidence in Concepts grant 2015-2017 Development of novel biologics-based antifungal therapeutics and diagnostics targeted towards Candida albicans cell surface glycoproteins.
SULSA MSD Postdoctoral grant with Dundee Drug Disovery Unit 2013-2015. Developing chitin synthase inhibitors.
BBSRC Case studentship with NovaBiotics, Prof. Ruth Ross, Prof Tony Ormerod. 2011-2015 Development of a bacterial-skin infection model to optimise the treatment and improve our understanding of persistent infections.
SULSA BioSkape industrial studentship with NovaBiotics Ltd 2010-2014
Antifungal peptide drugs. Knowledge Transfer Partnership with NovaBiotics Ltd 2010-2012
The Candida albicans ORFeome project .Wellcome Trust Biomedical Resources grant 2009-2013 (Lead PI with Dr d'Enfert, Institut Pasteur)
Gilead Sciences sponsored industrial studentships 2006-2010, 2009-2012 (with Professor Gow)
Regulation of the biosynthesis of the cell wall skeleton of Candida albicans. Wellcome Trust project grant 2009-2012 (Co-PI with Professor Gow and Odds)
Antifungal drug screening programme. University of Aberdeen Commercialisation Award 2010
The role of fungal cell wall composition and remodelling in echinocandin drug tolerance and resistance. British Society for Antimicrobial Chemotherapy research grant 2010
- Further Info
Deputy Editor-In-Chief of FEMS Yeast Research.
Editor of Microbiology. Associate Editor of Fungal Genetics & Biology.
Chair of Advanced Lecture Course on Human Fungal Pathogens HFP2017.
Ad hoc reviewer for international journals: PLoS Pathogens, Molecular Microbiology, Journal Biological Chemistry, FEMS Microbiology Letters, Microbiology, Journal of Antimicrobial Chemotherapy, Medical Mycology, Mycoses, Antimicrobial Agents and Chemotherapy, Fungal Genetics and Biology, Eukaryotic Cell, Infection & Immunity, Yeast, Molecular Plant Microbe Interactions.
Postgraduate research coordinator for School of Medical Sciences, College of Life Sciences and Medicine Graduate School