Research Overview

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 proteomics approach to detect proteins in the cell wall under different environment conditions and in response to antifungal drugs. We are investigating the molecular mechanisms that regulate cell wall salvage pathways and alter cell wall architecutre and composition. We are using these approaches to compare the cell walls of drug sensitive and resistant fungal isolate to determine the impact on cell wall changes to antifungal resistance.  

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 am also developing antibodies against fungal cell surface proteins with the Scottish Biologics Facility as diagnostics and therapeutics against invasive fungal infections. 

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 have constructed 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.

Current Research

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. 

I am a partner in the EU -funded Innovative Training Network FunHoMic (Deciphering the fungus-host-microbiota interplay to improve the management of fungal infections). https://www.funhomic.eu/en 

Past Research

I was 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 developed antifungal drug resistance biomarkers using a proteomics approach. 

Collaborations

Dr Christophe D'Enfert Pasteur Institute, France, - C. albicans ORFeome and over-expression library.

 Dr Campbell Gourlay, University of Kent -  Investigating the role of mitochondrial electron transport chain function in fungal pathogenicity and drug resistance.

Dr Donna MaCallum, University of Aberdeen - Human skin ex-plant model to study fungal infections.

Dr Soumya Palliyl, Professor Andy Porter, Scottish Biologics Facility - Developing fungal cell surface targeting antibodies.

Dr Annika Scheynius, Karolinska Institute - Malassezia sympodialis interactions with the host.

Research Funding and Grants

EU FunHoMic Innovative Training Network 2019-2023 “Deciphering the fungus-host-microbiota interplay to improve the management of fungal infections” PI with Dr Alan Walker and Prof Al Brown.

NC3Rs Phd studentship 2019-2022. Modelling Candida albicans infection of the human gut using human intestinal organoid cultures. Co-PI with Dr Silvia Gratz and Dr Donna MacCallum

Gilead Investigator Led Study 2020-2021 Can echinocandin-induced tolerance mechanisms promote persistent, drug recalcitrant infections? PI with Dr Louise Walker

Leverhulme Trust/Royal Society Senior Research Fellowship 2019-2020 Unbiased functional genomics screens for the molecular dissection of Candida albicans pathobiology and cellular morphology.

SULSA Antimicrobial Resistance Seed Funding 2018-2019 Antifungal potential of compounds produced by thermophilic Actinobacteria from compost, upon strains of azole resistant Aspergillus fumigatus. Co-Pi with Dr Gillian Halket, University of Strathclyde.

Wellcome Trust Strategic Award International PhD Scholarship 2014-2018  Investigating the role of mitochondrial electron transport chain function in fungal pathogenicity and drug resistance. Co-PI with Dr Campbell Gourlay, University of Kent.

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  Evaluating clinical outcomes to Candida albicans biofilm formation in candidaemia patients. Co-PI with Prof Ramage, University of Glasgow.

EU OPATHY Innovative Training Network 2015-2019 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