51cg

External Memberships

Deputy Editor-In-Chief of FEMS Yeast Research.

FEMS delegate for the Microbiology Society

Microbiology Society Impact & Influence Committee

Honorary member of  British Society for Medical Mycology

Research Overview

I am leader of the Microbiology & Immunity Research Theme (Microbiology and Immunity) that is comprised of over 20 principal investigators split into 3 sections: Immunology; Immunotherapeutics; Microbial Pathogenesis reflecting our research interests. 

I am co-founder and CSO of Brigid Biologics (), designing and developing a new class of antifungal therapeutics against drug resistant fungal pathogens of global healthcare concern.

My research is focussed on investigating fungi that cause life-threatening and multi-drug resistant infections in humans with impaired immune function. I investigate the role of the fungal cell wall in interactions with the host and have built up expertise in cell wall biochemistry, proteomics and microscopy approaches to gain a deeper understanding of how the cell wall is built and maintained. My work has focused mainly on Candida albicans but I have also worked with a wider range of pathogens including several other Candida species, including Candida glabrata and Candida auris, Aspergillus fumigatus, Malassezia sympodialis, Exophilia, Fusarium, Trichophyton, Rhizopus and Sporothrix species.

The cell wall is an excellent target for new therapies containing many fungal-specific components that are not found in the human host. I am motivated to develop novel therapeutics that target the cell wall and in collaboration with Scottish Biologics Facility have developed fungal cell wall targeting antibodies that are protective in fungal infection models. We have recently filed a patent to protect IP of these reagents.

I also study antifungal drug resistance and tolerance and discovered that in response to treatment with the echinocandin class of antifungals, fungi can re-programme their cell walls, upregulating chitin production and reducing drug susceptibility. Alterations in cell wall composition, both polysaccharide and protein abundances can influence host interactions, which we study using live cell imaging of fungal:macrophage interactions. I am also interested in analysing genetic variability amongst clinical fungal isolates in order to understand how genetic variability impacts on cell surface variability and hence interactions with the host and other virulence properties, including host niche-specific fitness.  Over the last 4 years my group have developed and utilized novel infection models, for example a skin ex-plant model, a catheterized lab-grown skin model for biofilm -associated infections, a gut epithelium model and tissue organoids. These models allow us to mimic the host environment to study fungal:host interactions and fungal pathogenicity. My group have also constructed genomic platforms to study functional genomics of Candida albicans, providing the wider community with powerful molecur tools to study fungal pathogenesis. At the end of 2020 I opened a Biological Containment Level 3 viral laboratory to work with the SARS-CoV-2 virus, in response to the ongoing pandemic and have set up assays to measure anti-viral activity of compounds and treatments.

Current Research

I am a partner in the EU-funded HDM-Fun Horizon 2020 Framework Programme 2020-2024 Host directed medicine in invasive fungal infection. 

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). ESR Ann Kristin Kaune with Dr Alan Walker and ESR Nate Cole  

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

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

Development of fungal surface targeting antibodies. PhD student Mark Mawer (funded by University of ABerdeen) and Tyng Tan (funded by the MRC Centre for Medical Mycology, University of Exeter) with Dr Soumya Palliyil and Professor Andy Porter (Scottish Biologics Facility)

Drug induced tolerance mechanisms: a driver for fungal persistence?   PhD student Mark Peacock (funded by the MRC Centre for Medical Mycology, University of Exeter) with Professor Neil Gow and Dr Alessandra da Silva Dantas 

Past Research

I was a partner in the EU -funded Innovative Training Network OPATHY (From Omics to Patient: Improving Diagnostics of Pathogenic Yeasts)  Within this network we developed antifungal drug resistance biomarkers using a proteomics approach. 

Collaborations

Dr Neil McCarthy, QMUL - Candida albicans:gut interactions

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, 51cg - Human skin models to study fungal infections.

Dr Silvia Gratz & Donna MacCallum, 51cg - Gut epithelium and organoid models to study fungal invasion

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.

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. 51cg 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