Dr Alan Brown
Co Director of Education and Student Experience (DESE) / Senior Lecturer in Molecular Microbiology
A.R.Brown@exeter.ac.uk
5526
+44 (0)1392 725526
Geoffrey Pope 404
Geoffrey Pope Building, University of Exeter , Stocker Road, Exeter, EX4 4QD, UK
Overview
I am a molecular microbiologist interested in mechanisms of virulence and niche adaptation in pathogenic bacteria. Research programmes within my group are focused on defining how such mechanisms impact on host-microbe interactions during infection, with the aim of using this knowledge to guide the rational development of novel antimicrobial strategies.
I am a member of the Biochemistry & Molecular Microbiology research group.
Qualifications
2010 Postgraduate Certificate in Academic Practice, University of Exeter
2001 PhD, University of Edinburgh
1997 BSc (Hons) Medical Microbiology, University of Edinburgh
Career
2013-Present Senior Lecturer in Molecular Microbiology, School of Biosciences, University of Exeter
2008-2013 Lecturer in Molecular Microbiology, School of Biosciences, University of Exeter
2005-2008 Postdoctoral Fellow & Coordinator of the UK Cystic Fibrosis Microbiology Consortium, Centre for Infectious Diseases, University of Edinburgh
2003-2005 Postdoctoral Scientist, The Roslin Institute
2000-2003 Postdoctoral Research Associate, Dept. of Veterinary Pathology, University of Edinburgh
Research group links
Research
Research interests
My research primarily focuses on Pseudomonas aeruginosa and species of the Burkholderia genus, specifically Burkholderia pseudomallei and members of the Burkholderia cepacia complex (Bcc). P. aeruginosa and the Bcc are both formidable pathogens of the cystic fibrosis (CF) lung, whilst P. aeruginosa is also a significant cause of healthcare-associated infection. In contrast, B. pseudomallei is the causative agent of melioidosis, a disease which is endemic in parts of southeast Asia and northern Australia.
I am interested in the fundamental mechanisms that underlie the virulence of these organisms, how genome and transcriptome plasticity facilitates their adaptation to diverse niches, and how knowledge of these processes can guide the development of novel therapeutic strategies.
Research projects
1. Investigating the role and inter-connectedness of metal-responsive two-component systems.
Bacteria possess efficient mechanisms by which they can sense and respond to heavy metals, including zinc, silver and copper. These mechanisms frequently involve two-component systems (TCSs), which sense the extracellular environment and trigger an appropriate response (typically a transcriptional response). We are exploring such metal-responsive TCSs in Burkholderia and Pseudomonas species, investigating their role in metal resistance and the extent to which these systems are interconnected.
2. The sphingosine-1-phosphate axis in host-microbe interactions.
In collaboration with Prof. Dominic Campopiano of the University of Edinburgh's School of Chemistry, we have identified that B. pseudomallei encodes two putative sphingosine-1-phosphate lyase (S1PL) enzymes that irreversibly degrade sphingosine-1-phosphate (S1P). In mammals, S1P is an important bioactive sphingolipid metabolite with diverse roles in numerous pathways including the regulation of immune and inflammatory processes. We are investigating the role of these bacterial-encoded S1PLs in virulence and immune evasion. In addition, we are investigating whether therapeutic targeting of the S1P axis represents a viable immunomodulatory-based anti-infective strategy.
3. Epidemiology of P. aeruginosa in CF and non-CF bronchiectasis patients.
In collaboration with clinical colleagues at the Royal Devon & Exeter Hospital, we are assessing the epidemiology of P. aeruginosa in bronchiectasis patients (CF and non-CF). In addition, we aim to determine whether individual patients harbour multiple strains of P. aeruginosa and also assess the wider microbial diversity within non-CF bronchiectasis patients.
In addition, other research interests include:
- The interconnectedness and relative hierarchies of gene regulatory networks in P. aeruginosa;
- How members of the Bcc adapt during chronic infection of the CF airways, and how such adaptations impact on the host-pathogen interaction and ultimately the progression of disease.
Research networks
- Dr Dominic Campopiano, University of Edinburgh
- Prof. Aras Kadioglu, University of Liverpool
- Prof. Eshwar Mahenthiralingam, Cardiff University
- Dr Philip Mitchelmore, University of Exeter/Royal Devon & Exeter Hospital
- Dr Steve Porter, University of Exeter
- Prof. Chris Scotton, University of Exeter
- Dr Chris Sheldon, Royal Devon & Exeter Hospital
- Dr Nick Withers, Royal Devon & Exeter Hospital
Research grants
- 2012 BBSRC
Pseudomonas quinolone signal and two-component systems; Unravelling the intricate network of gene regulation in Pseudomonas aeruginosa - 2010 The Cystic Fibrosis Trust
'The impact of diabetes on the microbiology of cystic fibrosis lung disease' - 2010 Royal Society
Characterizing the aminoarabinose biosynthetic pathway of the Burkholderia genus; An Achilles� heel of a multi-resistant bacterial pathogen & biowarfare agent? - 2008 MRC
New Investigator Research Grant 'Novel transcriptional regulators of virulence in the genus Burkholderia'
Publications
Journal articles
External Engagement and Impact
Invited lectures
2015. Giving the host the slip: The role of sphingosine-1-phosphate lyases (S1PL) of Burkholderia pseudomallei. OnE Seminar Series, University of Cardiff.
2009. The evolving epidemiology of Burkholderia cepacia complex in CF lung infection: The 'B. multivorans story'. Presented at the Scottish Cystic Fibrosis Group Meeting, Stirling.
2009. Mechanisms of virulence and niche adaptation in the genus Burkholderia. University of Newcastle (Transplantation and Immunobiology Research Group meeting).
Workshops/Conferences organised
2009. Organising Committee for the 2nd South West and South Wales Regional Microbiology Forum, Exeter, 24th Sep 2009.
2005-2008. Coordinator of the UK Cystic Fibrosis Microbiology Consortium.
Teaching
I am Co-Director of Education & Student Experience for Biosciences, and am co-convenor for BIO2101 Advanced Microbiology. I also teach on BIO3079 Molecular Basis of Infection.Modules
2023/24
Supervision / Group
Alumni
- Dr Rafael Custodio
- Dr Carmen Denman
- Dr Josh Dyer
- Dr Philip Mitchelmore
- Dr Jack Plume
- Dr Matthew Robinson