Name: Dr. David Clarke
Position: Lecturer
T: 353 (0)21 4903624
F: 353 (0)21 4903101
E: david.clarke@ucc.ie
Biography
Academic Career
1985-1989: BSc in Biotechnology; Dublin City University
1989-1994: PhD, National University of Ireland, Maynooth
1994-1998: Post-doctoral research, Institut de Genetique et Micobiologie, University Paris-Sud
1998-2000: Lecturer (fixed-term), National University of Ireland Maynooth
2000-2007: Lecturer, Dept. of Biology and Biochemistry, University of Bath
2007-present: Lecturer, Dept. of Microbiology, University College Cork
Additional Positions and Awards
Principle Investigator, Alimentary Pharmabiotic Centre (APC), UCC
Editorial Board of FEMS Microbiology Letters (2006- )
Teaching areas
- Molecular Biology
- Two-component pathways
- Environmental Microbiology
Research interests and expertise
- Bacteria-host interactions
- Biofilm formation
- Signaling in bacteria
Research
Selected Recent Publications
Ferrieres, L., A. Thompson and D. J. Clarke (2009) Elevated levels of sigmaS inhibit biofilm formation in Escherichia coli: a role for the Rcs phosphorelay. Microbiology 155:3544-3553.
Waterfield, N., T. A. Ciche and D. Clarke (2009) Photorhabdus and a host of hosts. Annu Rev Microbiol 63:557-574.
Huang, Y. H., L. Ferrières and D. J. Clarke (2009) Comparative functional analysis of the RcsC sensor kinase from different Enterobacteriaceae. FEMS Microbiol Lett. 293:248-254.
Easom, C. A. and D. J. Clarke (2008) Motility is required for the competitive fitness of entomopathogenic Photorhabdus luminscens during insect infection. BMC Microbiol 8:168.
Clarke, D. J. (2008) Photorhabdus: a model for the analysis of pathogenicity and mutualism. Cell Microbiol 10:2159-2167.
Joyce, S. A., A. O. Brachmann, I. Glazer, L. Lango, G. Schwar, D. J. Clarke and H. B. Bode (2008) Bacterial biosynthesis of a multipotent stilbene. Angewandte chemie 47:1942-1945.
Hinchliffe, S. J., S. L. Howard, Y. Huang, D. J. Clarke and B. W. Wren (2008) The importance of the Rcs phosphorelay in the survival and pathogenesis of the enteropathogenic Yersinia. Microbiology 154:1117-1131.
Brachmann, A. O., S. A. Joyce, H. Jenke-Kodoma, G. Schwar, D. J. Clarke and H. B. Bode (2007) A type II polyketide synthase is responsible for anthraquinone biosynthesis in Photorhabdus luminescens. ChemBioChem 8:1721-1728.
Ferrieres, L. S. N. Aslam. R. M. Cooper and D. J. Clarke (2007) The yjbEFGH locus in Escherichia coli K-12 is an operon encoding proteins involved in exopolysaccharide production, Microbiology 153:1070-1080.
Goodrich-Blair, H. and D. J. Clarke (2007) Mutualism and pathogenicity in Xenorhabdus and Photorhabdus: two roads to the same destination. Mol Microbiol 64:260-268.
Eleftherianos, I., S. Boundy, S. A. Joyce, S. Aslam, J. W. Marshall, R. J. Cox, T. J. Simpson, D. J. Clarke, R. H. ffrench-Constant and S. E. Reynolds (2007) An antibiotic produced by an insect pathogenic bacterium suppresses host defences through phenoloxidase inhibition. Proc Natl Acad Sci (USA) 104:2419-2424.
Williams, J. S., M. Thomas and D. J. Clarke (2005) The gene stlA encodes a phenylalanine ammonia-lyase that is involved in the production of a stilbene antibiotic in Photorhabdus luminescens TT01. Microbiology 151:2543-2550.
Watson, R. J., S. A. Joyce, G. V. Spencer and D. J. Clarke (2005) The exbD gene of Photorhabdus temperata is required for full virulence in insects and symbiosis with the nematode, Heterorhabditis. Mol Microbiol 56:763-773.
Ferrieres, L. and D. J. Clarke (2003) The RcsC sensor kinase is required for normal biofilm formation in Escherichia coli K-12 and controls the expression of a regulon in response to growth on a solid surface. Mol Microbiol, 50:1665-1682.
Joyce, S. A. and D. J. Clarke (2003) A homologue of HexA in Photorhabdus controls pathogenicity, symbiosis and phenotypic variation. Mol Microbiol 47:1445-1457.
Research funding and grants
Science Foundation Ireland (SFI) RFP, 01/08/2007
Integrating metabolism and genomics: aromatic amino acid metabolism in Photorhabdus luminescens (07/RFP/GENF546)
Health Research Board (HRB), 01/10/2008
Molecular mechanisms of adherent-invasive Escherichia coli (AIEC) persistence in macrophages (RP/2008/41)
Alimentary Pharmabiotic Centre II (SFI-CSET), 01/01/2009
Funding through Core 4 (Genomics and Metagenomics)
Intestinal proteases: opportunities for drug discovery (IPODD). EU Framework 7, 01/11/2008
Research
Groups and collaborators
Photorhabdus
Catherine Easom
Lea Lango
E. coli and Crohn’s disease
Adam O’Driscoll
Aoife Thompson
Bioprospecting the human gut microbiome
Elaine Crowley
Marc McCarthy
Key External Collaborators
Prof Helge Bode, University of Frankfurt
Dr Ralf Heermann, LMU, Munich
Research Projects in the group
Photorhabdus
Photorhabdus is a Gram negative bacterium that is closely related to Escherichia coli and other important mammalian pathogens. However Photorhabdus does not infect humans but rather this bacterium is a highly virulent pathogen of insects. At the same time Photorhabdus also has a mutualistic (symbiotic) association with nematodes from the family Heterorhabditis. We are interested in understanding the molecular basis of the interactions between Photorhabdus and its different hosts. Key questions that we are asking include: what are the bacterial genes required for ach of these interactions and how is the expression of these gene regulated? We are particularly interested in understanding the role played by primary metabolism in controlling the life cycle of Photorhabdus and also mapping the links between primary metabolism and the production of a range of interesting bioactive secondary metabolites produced by the Photorhabdus genus.
E. coli and Crohn’s disease
Inflammatory bowel diseases (IBD) are chronic relapsing disorders of the gastrointestinal tract that include ulcerative colitis (UC) and Crohn’s disease (CD). Although the cause of CD is not fully understood it is thought to be due to a combination of both host (i.e. genetic) and environmental (i.e. bacteria) factors. Escherichia coli are well-known inhabitants of the human gut where the bacteria occupy a niche in the colon. Although generally considered to be commensal organisms some strains of E. coli have the ability to cause disease, either in the intestine (e.g. E. coli O157::H7) or at other sites (e.g. E. coli are the primary cause of urinary tract infections). Recently a new group of E. coli, called adherent and invasive E. coli (AIEC), has been implicated in CD. Unlike most other strains of E. coli AIEC have the ability to 1) attach to and invade epithelial cells and 2) persist and replicate within macrophages. We are particularly interested in understanding the molecular mechanisms underpinning these phenotypes with the aim of identifying potential drug targets for novel IBD therapies.
Bioprospecting the human gut microbiome.
The human gut contains 1013-1015 bacteria (i.e. the microbiome) that contribute a significant metabolic function to their host. The microbiome has been shown to play an important role in maintaining normal gut function, digesting certain nutrients and has also been implicated in obesity and diabetes. Only a small fraction of the microbiome has been cultured suggesting that a significant fraction of the metabolic function associated with the gut microbiome remains to be discovered. Therefore, using an approach based on functional metagenomic screens, we are undertaking targeted bioprospecting and biomining in the human gut microbiome for novel functions and bioactive molecules. To do this we are taking advantage of metagenomic libraries of the human gut microbiome and a robotics platform both available within the Alimentary Pharmabiotic Centre (APC).
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