Staff Profile
Dr James Connolly
MRC Career Development Award Fellow
- Personal Website: https://www.ncl.ac.uk/medical-sciences/research/institutes/biosciences/
- Address: Newcastle University Biosciences Institute (NUBI)
Catherine Cookson Building
Newcastle University
Framlington Place
Newcastle upon Tyne NE2 4HH
Research Career
Principal Research Associate (2024-onwards)
MRC Career Development Fellow (2023-2028)
Faculty of Medical Sciences Research Fellow (2019-2023)
Post-doctoral Research Associate, University of Glasgow (2015-2019)
Doctoral research, University of Glasgow (2011-2015)
Education
Post-doctoral research associate, University of Glasgow
PhD in Bacteriology, University of Glasgow
MRes in Medical and Veterinary Microbiology, University of Glasgow
BSc in Microbiology, University College Dublin
Honours and Awards
MRC Career Development Award (2023-2028)
Royal Society Research Grant (2020-2021)
Academy of Medical Sciences Springboard Award (2020-2023)
Research interests
Bacterial pathogens
Gene regulation
Mechanisms of disease
My lab studies bacterial pathogenesis using Escherichia coli and Citrobacter rodentium as model organisms. These species are comprised of both harmless commensals and distinct 'pathotypes' that are associated with disease and infection of discreet host sites - including the gut, the urinary tract and the bloodstream. The ability to infect such distinct host sites is driven by a combination of virulence factor expression and lifestyle adaptations that permit growth. My research is focused on deciphering how these processes are controlled at the host-pathogen interface. There are 3 key questions:
1) How is gene expression regulated in response to different host-niches?
2) What are the underlying mechanisms driving regulatory adaptation?
3) How do these regulatory adaptations impact on the virulence and evolution of distinct bacterial pathogens?
We use next-generation sequencing techniques such as RNA-seq and ChIP-seq to study global gene regulatory networks. These approaches are combined with classical bacterial physiology, genetic and cell biology approaches to study individual regulatory mechanisms in detail. We also employ several murine models of infection allowing us to investigate gene expression directly at the host-interface (in vivo RNA-seq) and the contribution of individual genes to host colonisation. The overarching aim is to deepen our understanding of bacterial pathogenesis, which could potentially lead to the design of novel therapeutic strategies against these pathogens.
Current lab members
Dr Curtis Cottam (Postdoctoral research associate)
Kieran Bowran (Postdoctoral research assistant; co-supervised with Dr Manuel Banzhaf)
Chloe Ellison (PhD student)
I am always keen to hear from prospective PhD candidates and encourage students interested in our research to get in touch about potential opportunities.
Teaching and Supervision
CMB1003 - Microbiology and Immunology
PSC3013 - Physiology of the Gastrointestinal Tract
CMB3000 - Undergraduate research project supervision
4828F - MRes Molecular Microbiology research project supervision
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Articles
- Cottam C, White RT, Beck LC, Stewart CJ, Beatson SA, Lowe EC, Grinter R, Connolly JPR. Metabolism of l-arabinose converges with virulence regulation to promote enteric pathogen fitness. Nature Communications 2024, 15, 4462.
- Helena-Bueno K, Rybak MY, Ekemezie CL, Sullivan R, Brown CR, Dingwall C, Basle A, Schneider C, Connolly JP, Blaza JN, Csorgo B, Moynihan PJ, Gagnon MG, Hill CH, Melnikov SV. A new family of bacterial ribosome hibernation factors. Nature 2024, (ePub ahead of Print).
- Macdonald E, Wright R, Connolly JPR, Strahl H, Brockhurst M, van Houte S, Blower TR, Palmer T, Mariano G. The novel anti-phage system Shield co-opts an RmuC domain to mediate phage defense across Pseudomonas species. PLoS Genetics 2023, 19(6), e1010784.
- Macdonald E, Wright R, Connolly JPR, Strahl H, Brockhurst M, van Houte S, Blower TR, Palmer T, Mariano G. The novel anti-phage system Shield co-opts an RmuC domain to mediate phage defense across Pseudomonas species. PLOS Genetics 2023, 19(6), e1010784.
- O'Boyle N, Douce GR, Farrell G, Rattray NJW, Schembri MA, Roe AJ, Connolly JPR. Distinct ecological fitness factors coordinated by a conserved Escherichia coli regulator during systemic bloodstream infection. Proceedings of the National Academy of Sciences of the United States of America 2023, 120(1), e2212175120.
- Connolly JPR, Turner NCA, Serrano E, Rimbi PT, Browning DF, O'Boyle N, Roe AJ. Control of resistance against bacteriophage killing by a metabolic regulator in meningitis-associated Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America 2022, 119(45), e2210299119.
- An S-Q, Lopes BS, Connolly JPR, Sharp C, Nguyen TKL, Kirkpatrick CL. Going virtual: A report from the sixth Young Microbiologists Symposium on ‘Microbe Signalling, Organisation and Pathogenesis’. Microbiology 2021, 167(3), 001024.
- Connolly JPR, Turner NCA, Hallam JC, Rimbi PT, Flett T, McCormack MJ, Roe AJ, O'Boyle N. d-Serine induces distinct transcriptomes in diverse Escherichia coli pathotypes. Microbiology 2021, 167(10).
- Connolly JPR, O'boyle N, Roe AJ. Widespread strain-specific distinctions in chromosomal binding dynamics of a highly conserved Escherichia coli transcription factor. mBio 2020, 11(3), 1-6.
- Ormsby MJ, Johnson SA, Carpena N, Meikle LM, Goldstone RJ, McIntosh A, Wessel HM, Hulme HE, McConnachie CC, Connolly JPR, Roe AJ, Hasson C, Boyd J, Fitzgerald E, Gerasimidis K, Morrison D, Hold GL, Hansen R, Walker D, Smith DGE, Wall DM. Propionic Acid Promotes the Virulent Phenotype of Crohn’s Disease-Associated Adherent-Invasive Escherichia coli . Cell Reports 2020, 30(7), 2297-2305.e5.
- O'Boyle N, Connolly JPR, Tucker NP, Roe AJ. Genomic plasticity of pathogenic Escherichia coli mediates D-serine tolerance via multiple adaptive mechanisms. Proceedings of the National Academy of Sciences of the United States of America 2020, 117(36), 22484-22493.
- Irvine S, Bunk B, Bayes HK, Sproer C, Connolly JPR, Six A, Evans TJ, Roe AJ, Overmann J, Walker D. Genomic and transcriptomic characterization of Pseudomonas aeruginosa small colony variants derived from a chronic infection model. Microbial Genomics 2019, 5(4), 1-11.
- Connolly JPR, O'Boyle N, Turner NCA, Browning DF, Roe AJ. Distinct intraspecies virulence mechanisms regulated by a conserved transcription factor. Proceedings of the National Academy of Sciences of the United States of America 2019, 116(39), 19695-19704.
- McHugh RE, O'Boyle N, Connolly JPR, Hoskisson PA, Roe AJ. Characterization of the mode of action of aurodox, a type III secretion system inhibitor from Streptomyces goldiniensis. Infection and Immunity 2019, 87(2), e00595-18.
- Blum SE, Goldstone RJ, Connolly JPR, Reperant-Ferter M, Germon P, Inglis NF, Krifucks O, Mathur S, Manson E, Mclean K, Rainard P, Roe AJ, Leitner G, Smith DGE. Postgenomics characterization of an essential genetic determinant of mammary pathogenic Escherichia coli. mBio 2018, 9(2), e00423-18.
- Connolly JPR, Slater SL, O'Boyle N, Goldstone RJ, Crepin VF, Ruano-Gallego D, Herzyk P, Smith DGE, Douce GR, Frankel G, Roe AJ. Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion. Nature Communications 2018, 9(1), 4187.
- Scott NA, Andrusaite A, Andersen P, Lawson M, Alcon-Giner C, Leclaire C, Caim S, Le Gall G, Shaw T, Connolly JPR, Roe AJ, Wessel H, Bravo-Blas A, Thomson CA, Kastele V, Wang P, Peterson DA, Bancroft A, Li X, Grencis R, McI Mowat A, Hall LJ, Travis MA, Milling SWF, Mann ER. Antibiotics induce sustained dysregulation of intestinal T cell immunity by perturbing macrophage homeostasis. Science Translational Medicine 2018, 10(464), eaao4755.
- Zambelloni R, Connolly JPR, Huerta Uribe A, Burgess K, Marquez R, Roe AJ. Novel compounds targeting the enterohemorrhagic Escherichia coli type three secretion system reveal insights into mechanisms of secretion inhibition. Molecular Microbiology 2017, 105(4), 606-619.
- Palevsky N, Shemer B, Connolly JPR, Belkin S. The highly conserved Escherichia coli transcription factor YhaJ regulates aromatic compound degradation. Frontiers in Microbiology 2016, 7, 1490.
- Connolly JPR, Roe AJ. Intracellular D-serine accumulation promotes genetic diversity via modulated induction of RecA in enterohemorrhagic Escherichia coli. Journal of Bacteriology 2016, 198(24), 3318-3328.
- Huerta-Uribe A, Marjenberg ZR, Yamaguchi N, Fitzgerald S, Connolly JPR, Carpena N, Uvell H, Douce G, Elofsson M, Byron O, Marquez R, Gally DL, Roe AJ. Identification and characterization of novel compounds blocking Shiga toxin expression in Escherichia coli O157:H7. Frontiers in Microbiology 2016, 7, 1930.
- Connolly JPR, Gabrielsen M, Goldstone RJ, Grinter R, Wang D, Cogdell RJ, Walker D, Smith DGE, Roe AJ. A Highly Conserved Bacterial D-Serine Uptake System Links Host Metabolism and Virulence. PLoS Pathogens 2016, 12(1), e1005359.
- Connolly JPR, Goldstone RJ, Burgess K, Cogdell RJ, Beatson SA, Vollmer W, Smith DGE, Roe AJ. The host metabolite D-serine contributes to bacterial niche specificity through gene selection. The ISME Journal 2015, 9(4), 1039-1051.
- Beckham KSH, Connolly JPR, Ritchie JM, Wang D, Gawthorne JA, Tahoun A, Gally DL, Burgess K, Burchmore RJ, Smith BO, Beatson SA, Byron O, Wolfe AJ, Douce GR, Roe AJ. The metabolic enzyme AdhE controls the virulence of Escherichia coli O157: H7. Molecular Microbiology 2014, 93(1), 199-211.
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Notes
- Connolly JPR, Slater SL, O'Boyle N, Goldstone RJ, Crepin VF, Ruano-Gallego D, Herzyk P, Smith DGE, Douce GR, Frankel G, Roe AJ. Author correction: Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion (Nature Communications, (2018), 9, 1, (4187), 10.1038/s41467-018-06701-4). Nature Communications 2018, 9(1), 5148.
- Connolly JPR, Goldstone RJ, Burgess K, Cogdell RJ, Beatson SA, Vollmer W, Smith DGE, Roe AJ. Erratum: The host metabolite D-serine contributes to bacterial niche specificity through gene selection (ISME Journal (2015) 9 (1039-1051) DOI: 10.1038/ismej.2014.242). The ISME Journal 2015, 9, 1052-1052.
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Reviews
- Connolly JPR, Roe AJ, O'Boyle N. Prokaryotic life finds a way: insights from evolutionary experimentation in bacteria. Critical Reviews in Microbiology 2021, 47(1), 126-140.
- O'Boyle N, Turner NCA, Roe AJ, Connolly JPR. Plastic Circuits: Regulatory Flexibility in Fine Tuning Pathogen Success. Trends in Microbiology 2020, 28(5), 360-371.
- O'Boyle N, Connolly JPR, Roe AJ. Tracking elusive cargo: Illuminating spatio-temporal Type 3 effector protein dynamics using reporters. Cellular Microbiology 2018, 20(1), e12797.
- Turner NCA, Connolly JPR, Roe AJ. Control freaks—signals and cues governing the regulation of virulence in attaching and effacing pathogens. Biochemical Society Transactions 2018, 47(1), 229-238.
- Connolly JPR, Roe AJ. When and where? Pathogenic Escherichia coli differentially sense host D-serine using a universal transporter system to monitor their environment. Microbial Cell 2016, 3(4), 181-184.
- Connolly JPR, Brett Finlay B, Roe AJ. From ingestion to colonization: The influence of the host environment on regulation of the LEE encoded type III secretion system in enterohaemorrhagic Escherichia coli. Frontiers in Microbiology 2015, 6, 658.