Lecturer
Microbiology
University College Cork
Cork
Ireland

T: 353 (0)21 4903624
F: 353 (0)21 4903101
E: david.clarke@ucc.ie
Principal Investigator
Alimentary Pharmabotic Centre (Apc)
University College Cork
Cork
Ireland

T: +353 (0)21 4903624
E: david.clarke@ucc.ie

David Clarke graduated with a B.Sc in Biotechnology from Dublin City University in 1989. From here he went to the National University of Ireland in Maynooth to undertake a PhD in Microbiology, graduating in 1993. He then traveled to France where he was awarded an International Traveling Prize Fellowship by the Wellcome Trust to undertake post-doctoral research in the laboratory of Professor Barry Holland who was based at the Institut de Genetique et Microbiologie, Universite Paris-Sud. In September 1998 David briefly returned to the Department of Biology at NUI Maynooth before joining the faculty of the Department of Biology and Biochemistry at the University of Bath, UK as a Lecturer in January 2000. He was promoted to Senior Lecturer in September 2004 before finally returning to Ireland in February 2007 as a College Lecturer in the Department of Microbiology at UCC. Dr Clarke is also a Principal Investigator in the Alimentary Pharmabiotic Centre (APC, http://apc.ucc.ie)

Research Interests

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).



Research Projects

 Project (ID))RoleDescriptionStart DateEnd Date
Characterization of choA, a gene encodong a novel cholesterol degrading activity from the human gut microbiome ()01-APR-1331-MAR-17
individual consumable budget. (R14699)Principal InvestigatorUC01-MAR-1130-SEP-15
SFI CSET Programme 2 - High Throughput Analysis Platform B (R13020)Principal InvestigatorUC01-NOV-0831-OCT-13
SFI CSET Programme 2 - Genomics & Metagenomics Core 4c (R13017)Principal InvestigatorUC01-NOV-0831-OCT-13
Moleacular Mechanisms of Adherent Invasive Escherichia Coli (AIEC) Persistance in Macronphag... (R12785)Principal InvestigatorUC30-AUG-0830-SEP-11
SFI-Integrating metabolism and genomics: aromatic amino acid metabolism in photorhabus luminescence (R12224)Principal InvestigatorUC01-AUG-0731-DEC-10

Book Chapters

YearPublication
(2012)'Nematode parasites and entomopathogens'
Lewis, E. E. and Clarke, D. J. (2012) 'Nematode parasites and entomopathogens' In: Vega, F. E. and Kaya, H. K (eds). Insect Pathology. London, UK: Academic Press. [No details]
(2012)'The Rcs phosphorelay: biofilm formation and virulence in the Enterobacteriaceae'
Clarke, D. J. (2012) 'The Rcs phosphorelay: biofilm formation and virulence in the Enterobacteriaceae' In: Gross, R. and Beier, D (eds). Two-component systems in bacteria. Norfolk, UK: Caister Academic Press. [No details]
(2006)'Bacteria-nematode associations'
Clarke, D. J. and L. Eberl ; (2006) 'Bacteria-nematode associations' In: Konig, H. and A. Varma (eds). Intestinal microorganisms of termites and other invertebrates (Soil Biology). Springer. [No details]
(2002)'Bacteria-nematode symbiosis'
Forst, S. and D. J. Clarke ; (2002) 'Bacteria-nematode symbiosis' In: Guagler, R., and Kaya, H (eds). Entomopathogenic nematodes. CABI Press. [No details]

Peer Reviewed Journals

YearPublication
(2013)'Pathogenesis of adherent-invasive Escherichia coli'
Smith, EJ, Thompson, AP, O'Driscoll, A, and Clarke, DJ (2013) 'Pathogenesis of adherent-invasive Escherichia coli' [Details]
(2013)'The expression of stlA in Photorhabdus luminescens is controlled by nutrient limitation'
Lango-Scholey, L, Brachmann, AO, Bode, HB, and Clarke, DJ (2013) 'The expression of stlA in Photorhabdus luminescens is controlled by nutrient limitation' [Details]
(2012)'HdfR is a regulator in Photorhabdus luminescens that modulates metabolism and symbiosis with the nematode Heterorhabditis'
Easom, CA,Clarke, DJ (2012) 'HdfR is a regulator in Photorhabdus luminescens that modulates metabolism and symbiosis with the nematode Heterorhabditis' [DOI] [Details]
(2011)'The Regulation of Secondary Metabolism and Mutualism in the Insect Pathogenic Bacterium Photorhabdus luminescens'
Joyce SA, Lango L, Clarke DJ (2011) 'The Regulation of Secondary Metabolism and Mutualism in the Insect Pathogenic Bacterium Photorhabdus luminescens' [DOI] [Details]
(2011)'Complete genome sequence of the Crohn's disease-associated adherent-invasive Escherichia coli strain HM605'
Clarke DJ, Chaudhuri RR, Martin HM, Campbell BJ, Rhodes JM, Constantinidou C, Pallen MJ, Loman NJ, Cunningham AF, Browning DF, Henderson IR (2011) 'Complete genome sequence of the Crohn's disease-associated adherent-invasive Escherichia coli strain HM605' [DOI] [Details]
(2011)'Degradation of the Extracellular Matrix Components by Bacterial-derived Metalloproteases: Implications for Inflammatory Bowel Diseases'
Pruteanu, Mihaela and Hyland, Niall P. and Clarke, David J. and Kiely, Barry and Shanahan, Fergus (2011) 'Degradation of the Extracellular Matrix Components by Bacterial-derived Metalloproteases: Implications for Inflammatory Bowel Diseases' [Details]
(2010)'Identification of genes involved in the mutualistic colonization of the nematode Heterorhabditis bacteriophora by the bacterium Photorhabdus luminescens'
Easom, CA; Joyce, SA; Clarke, DJ; (2010) 'Identification of genes involved in the mutualistic colonization of the nematode Heterorhabditis bacteriophora by the bacterium Photorhabdus luminescens' [DOI] [Details]
(2010)'A metabolic switch is involved in lifestyle decisions in Photorhabdus luminescens'
Lango, L; Clarke, DJ; (2010) 'A metabolic switch is involved in lifestyle decisions in Photorhabdus luminescens' [Details]
(2010)'The role of iron uptake in pathogenicity and symbiosis in Photorhabdus luminescens TT01'
Watson, RJ; Millichap, P; Joyce, SA; Reynolds, SE; Clarke, DJ; (2010) 'The role of iron uptake in pathogenicity and symbiosis in Photorhabdus luminescens TT01' [DOI] [Full Text] [Details]
(2010)'The Rcs phosphorelay: more than just a two-compoent pathway'
Clarke, DJ; (2010) 'The Rcs phosphorelay: more than just a two-compoent pathway' [Details]
(2010)'Dissecting the immune response to the entomopathogen Photorhabdus'
Eleftherianos I, ffrench-Constant RH, Clarke DJ, Dowling AJ, Reynolds SE (2010) 'Dissecting the immune response to the entomopathogen Photorhabdus' [DOI] [Details]
(2010)'Probing the tritrophic interaction between insects, nematodes and Photorhabdus'
Eleftherianos, I; Joyce, SA; ffrench-Constant, RH; Clarke, DJ; Reynolds, SE ; (2010) 'Probing the tritrophic interaction between insects, nematodes and Photorhabdus' [Details]
(2009)'Comparative functional analysis of the RcsC sensor kinase from different Enterobacteriaceae'
Huang, Y. H.,Ferrieres, L.,Clarke, D. J.; (2009) 'Comparative functional analysis of the RcsC sensor kinase from different Enterobacteriaceae' [Details]
(2009)'Photorhabdus and a host of hosts'
Waterfield, N. R.,Ciche, T.,Clarke, D.; (2009) 'Photorhabdus and a host of hosts' [Details]
(2009)'Comparative functional analysis of the RcsC sensor kinase from different Enterobacteriaceae'
Huang, YH,Ferrieres, L,Clarke, DJ; (2009) 'Comparative functional analysis of the RcsC sensor kinase from different Enterobacteriaceae' [DOI] [Details]
(2009)'Heterorhabditis gerrardi n. sp. (Nematoda: Heterorhabditidae): the hidden host of Photorhabdus asymbiotica (Enterobacteriaceae: gamma-Proteobacteria)'
Plichta, K. L., Joyce, S. A., Clarke, D. J., Waterfield, N. and Stock, S. P. ; (2009) 'Heterorhabditis gerrardi n. sp. (Nematoda: Heterorhabditidae): the hidden host of Photorhabdus asymbiotica (Enterobacteriaceae: gamma-Proteobacteria)' [Details]
(2009)'Elevated levels of sigma S inhibit biofilm formation in Escherichia coli: a role for the Rcs phosphorelay'
Ferrieres, L; Thompson, A; Clarke, DJ; (2009) 'Elevated levels of sigma S inhibit biofilm formation in Escherichia coli: a role for the Rcs phosphorelay' [Details]
(2008)'Photorhabdus: a model for the analysis of pathogenicity and mutualism'
Clarke, D. J.; (2008) 'Photorhabdus: a model for the analysis of pathogenicity and mutualism' [Details]
(2008)'The importance of the Rcs phosphorelay in the survival and pathogenesis of the enteropathogenic yersiniae. Microbiology'
Hinchliffe, S. J.,Howard, S. L.,Huang, Y. H.,Clarke, D. J.,Wren, B. W.; (2008) 'The importance of the Rcs phosphorelay in the survival and pathogenesis of the enteropathogenic yersiniae. Microbiology' [Details]
(2008)'Bacterial biosynthesis of a multipotent stilbene'
Joyce, S. A.,Brachmann, A. O.,Glazer, I.,Lango, L.,Schwar, G.,Clarke, D. J.,Bode, H. B.; (2008) 'Bacterial biosynthesis of a multipotent stilbene' [Details]
(2008)'Motility is required for the competitive fitness of entomopathogenic Photorhabdus luminescens during insect infection. BMC Microbiol'
Easom, C. A.,Clarke, D. J.; (2008) 'Motility is required for the competitive fitness of entomopathogenic Photorhabdus luminescens during insect infection. BMC Microbiol' [DOI] [Details]
(2007)'A type II polyketide synthase is responsible for anthraquinone biosynthesis in Photorhabdus luminescens'
Brachmann, A. O.,Joyce, S. A.,Jenke-Kodama, H.,Schwar, G.,Clarke, D. J.,Bode, H. B.; (2007) 'A type II polyketide synthase is responsible for anthraquinone biosynthesis in Photorhabdus luminescens' [Details]
(2007)'The yjbEFGH locus in Escherichia coli K-12 is an operon encoding proteins involved in exopolysaccharide production'
Ferrieres, L.,Aslam, S. N.,Cooper, R. M.,Clarke, D. J.; (2007) 'The yjbEFGH locus in Escherichia coli K-12 is an operon encoding proteins involved in exopolysaccharide production' [Details]
(2007)'Mutualism and pathogenesis in Xenorhabdus and Photorhabdus: two roads to the same destination'
Goodrich-Blair, H.,Clarke, D. J.; (2007) 'Mutualism and pathogenesis in Xenorhabdus and Photorhabdus: two roads to the same destination' [Details]
(2007)'An antibiotic produced by an insect-pathogenic bacterium suppresses host defenses through phenoloxidase inhibition'
Eleftherianos, I.,Boundy, S.,Joyce, S. A.,Aslam, S.,Marshall, J. W.,Cox, R. J.,Simpson, T. J.,Clarke, D. J.,ffrench-Constant, R. H.,Reynolds, S. E.; (2007) 'An antibiotic produced by an insect-pathogenic bacterium suppresses host defenses through phenoloxidase inhibition' [Details]
(2006)'The role of the Rcs phosphorelay in Enterobacteriaceae'
Huang, Y. H.,Ferrieres, L.,Clarke, D. J.; (2006) 'The role of the Rcs phosphorelay in Enterobacteriaceae' [Details]
(2006)'The regulation of pathogenicity and mutualism in Photorhabdus'
Joyce, S. A.,Watson, R. J.,Clarke, D. J.; (2006) 'The regulation of pathogenicity and mutualism in Photorhabdus' [Details]
(2005)'The pbgPE operon in Photorhabdus luminescens is required for pathogenicity and symbiosis'
Bennett, H. P.,Clarke, D. J.; (2005) 'The pbgPE operon in Photorhabdus luminescens is required for pathogenicity and symbiosis' [Details]
(2005)'The exbD gene of Photorhabdus temperata is required for full virulence in insects and symbiosis with the nematode Heterorhabditis'
Watson, R. J.,Joyce, S. A.,Spencer, G. V.,Clarke, D. J.; (2005) 'The exbD gene of Photorhabdus temperata is required for full virulence in insects and symbiosis with the nematode Heterorhabditis' [Details]
(2005)'The gene stlA encodes a phenylalanine ammonia-lyase that is involved in the production of a stilbene antibiotic in Photorhabdus luminescens TT01'
Williams, J. S.,Thomas, M.,Clarke, D. J.; (2005) 'The gene stlA encodes a phenylalanine ammonia-lyase that is involved in the production of a stilbene antibiotic in Photorhabdus luminescens TT01' [Details]
(2004)'Study of the attachment of Pseudomonas aeruginosa on gold and modified gold surfaces using surface plasmon resonance'
Jenkins, A. T.,ffrench-constant, R.,Buckling, A.,Clarke, D. J.,Jarvis, K.; (2004) 'Study of the attachment of Pseudomonas aeruginosa on gold and modified gold surfaces using surface plasmon resonance' [Details]
(2003)'Photorhabdus: towards a functional genomic analysis of a symbiont and pathogen'
ffrench-Constant, R.,Waterfield, N.,Daborn, P.,Joyce, S.,Bennett, H.,Au, C.,Dowling, A.,Boundy, S.,Reynolds, S.,Clarke, D.; (2003) 'Photorhabdus: towards a functional genomic analysis of a symbiont and pathogen' [Details]
(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'
Ferrieres, L.,Clarke, D. J.; (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' [Details]
(2003)'A hexA homologue from Photorhabdus regulates pathogenicity, symbiosis and phenotypic variation'
Joyce, S. A.,Clarke, D. J.; (2003) 'A hexA homologue from Photorhabdus regulates pathogenicity, symbiosis and phenotypic variation' [Details]
(2003)'The transmembrane domain of the DnaJ-like protein DjlA is a dimerisation domain'
Toutain, C. M.,Clarke, D. J.,Leeds, J. A.,Kuhn, J.,Beckwith, J.,Holland, I. B.,Jacq, A.; (2003) 'The transmembrane domain of the DnaJ-like protein DjlA is a dimerisation domain' [Details]
(2002)'Genetic analysis of the RcsC sensor kinase from Escherichia coli K-12'
Clarke, D. J.,Joyce, S. A.,Toutain, C. M.,Jacq, A.,Holland, I. B.; (2002) 'Genetic analysis of the RcsC sensor kinase from Escherichia coli K-12' [Details]
(2002)'The ner gene of Photorhabdus: effects on primary-form-specific phenotypes and outer membrane protein composition'
O'Neill, K. H.,Roche, D. M.,Clarke, D. J.,Dowds, B. C.; (2002) 'The ner gene of Photorhabdus: effects on primary-form-specific phenotypes and outer membrane protein composition' [Details]
(1998)'Increased sensitivity of E. coli to novobiocin, EDTA and the anticalmodulin drug W7 following overproduction of DjlA requires a functional transmembrane domain'
Bernard, S.,Clarke, D. J.,Chen, M. X.,Holland, I. B.,Jacq, A.; (1998) 'Increased sensitivity of E. coli to novobiocin, EDTA and the anticalmodulin drug W7 following overproduction of DjlA requires a functional transmembrane domain' [Details]
(1997)'Point mutations in the transmembrane domain of DjlA, a membrane-linked DnaJ-like protein, abolish its function in promoting colanic acid production via the Rcs signal transduction pathway'
Clarke, D. J.,Holland, I. B.,Jacq, A.; (1997) 'Point mutations in the transmembrane domain of DjlA, a membrane-linked DnaJ-like protein, abolish its function in promoting colanic acid production via the Rcs signal transduction pathway' [Details]
(1996)'The gram-negative cell envelope 'springs' to life: coiled-coil trans-envelope proteins'
Pimenta, A.,Blight, M.,Clarke, D.,Holland, I. B.; (1996) 'The gram-negative cell envelope 'springs' to life: coiled-coil trans-envelope proteins' [Details]
(1996)'A novel DnaJ-like protein in Escherichia coli inserts into the cytoplasmic membrane with a type III topology'
Clarke, D. J.,Jacq, A.,Holland, I. B.; (1996) 'A novel DnaJ-like protein in Escherichia coli inserts into the cytoplasmic membrane with a type III topology' [Details]
(1995)'The relationship between growth rate of Photorhabdus sp. strain K122 and pathogenicity to Galleria mellonella (Waxmoth) larvae: the possible role of extracellular enzymes in pathogenicity'
Clarke, D. J., and B. C. A. Dowds ; (1995) 'The relationship between growth rate of Photorhabdus sp. strain K122 and pathogenicity to Galleria mellonella (Waxmoth) larvae: the possible role of extracellular enzymes in pathogenicity' [Details]
(1994)'The gene coding for polynucleotide phosphorylase in Photorhabdus sp. strain K122 is induced at low temperatures'
Clarke, D. J.,Dowds, B. C.; (1994) 'The gene coding for polynucleotide phosphorylase in Photorhabdus sp. strain K122 is induced at low temperatures' [Details]
(1992)'Isolation/generation of cold active strains of Xenorhabdus luminescens, the symbiont of entomopathogenic nematodes of the genus Heterorhabditis'
Clarke, D. J., H. Wang, and B. C. A. Dowds. ; (1992) 'Isolation/generation of cold active strains of Xenorhabdus luminescens, the symbiont of entomopathogenic nematodes of the genus Heterorhabditis' [Details]
(1992)'Pathogenicity of Xenorhabdus luminescens'
Clarke, D. J.,Dowds, B. C.; (1992) 'Pathogenicity of Xenorhabdus luminescens' [Details]

Conference Publications

YearPublication
(1994)Genetics of Entomopathogenic Nematode - Bacterium Complexes. Proceedings of a COST symposium and workshops
Clarke, D. J., and B. C. A. Dowds; (1994) Cold acclimation in Photorhabdus spp . In: Burnell, A., Ehlers, R. -U., and Masson, J. -P. E eds. Genetics of Entomopathogenic Nematode - Bacterium Complexes. Proceedings of a COST symposium and workshops St. Patricks College, Maynooth, Co. Kildare, Ireland, , 23-OCT-93 - 25-OCT-93 , pp.170-177 [Details]

Associations

 AssocationFunctionFrom / To
Society for General Microbiology Member/
American Society for Microbiology Member/

Committees

 CommitteeFunctionFrom / To
Society for General Microbiology Prokaryotic Division Committee member2010 /

Consultancy

 ClientDescription
Ad hoc reviewer for international funding agencies and journals
Ad hoc reviewer for following funding agencies: BBSRC, Wellcome Trust, NSF

Ad hoc reviewer for following journals: Molecular Microbiology, Journal of Bacteriology, Cellular Microbiology, Microbiology

Reviews

 JournalRole
Fems Microbiology Letters Member of Editorial Board

Current Postgraduate Students

O Neill Ian JamesDoctoral Degree (Structured)

Modules Taught

 Term (ID))TitleLinkSubject
2014Research Frontiers in Food Microbiology MB6027Research Frontiers in Food Microbiology
2014Research Project MB4002Research Project
2014Environmental Systems Microbiology: Themes in microbe-host interactions MB3017Environmental Systems Microbiology: Themes in microbe-host interactions
2014Molecular Genetics and Genomics MB3007Molecular Genetics and Genomics
2014Microbial Diversity and Ecology MB4022Microbial Diversity and Ecology
2014Medical Microbiology MB3001Medical Microbiology
2014Medical Microbiology MB3901Medical Microbiology
2014Literature Project on Genetics GN3002Literature Project on Genetics
2014Research Dissertation MB6303Research Dissertation
2014Environmental Microbial Genomics II: understanding and exploiting microbial communities MB4020Environmental Microbial Genomics II: understanding and exploiting microbial communities
2014Research Frontiers in Microbiology MB4027Research Frontiers in Microbiology
2014Molecular Biology and Physiology of Bacteria MB4026Molecular Biology and Physiology of Bacteria