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Trinity College Dublin

Personal Information
Name Smith, Stephen
Main Department Clinical Microbiology
College Title Assistant Professor
E-mail sgsmith@tcd.ie
College Tel +353 1 896 8590
Web http://www.medicine.tcd.ie/clinical_microbiology/research/smith.php
 
Membership of Professional Institutions, Associations, Societies
Details Date From Date To
Member Society for General Microbiology UK
Member American Society for Microbiology
 
Languages
Language Skill Reading Skill Writing Skill Speaking
English Fluent Fluent Fluent
French Basic Basic Basic
 
Description of Research Interests
My laboratory investigates how gram-negative bacteria, in particular E. coli and Salmonella, attach to and invade human cells. We are currently using Cellomics-based approaches to more accurately quantify bacterial invasion. This methodology also generates information on the kinetics of invasion and the cellular location of the invading bacteria. We are also interested in the gene regulatory mechanisms that govern attachment by E. coli e.g. the Rns virulence regulator.Invasion of cellular barriers by bacteria can be a prelude to entrance into the bloodstream. We are using transcriptomics to identify genes in E. coli that are regulated in response to human serum and its anti-bacterial components. More recently, and in collaboration with the Royal College of Surgeons in Ireland, we have shown that human estrogen can modulate the virulence of Pseudomonas aeruginosa.
 
Research Interests
Antibiotics Biological Markers Brain Cell Communication
DNA Diagnostics Digestive System E.coli
Eschericia coli Extracellular Matrix Gastrointestinal Diseases/Disorders Gene Expression
Gene Regulation Genetically Modified Organisms Genomes, Genomics Infectious Diseases
Infectious Diseases/Agents Meningitis Microbial Biotechnology, Microbial Modelling Molecular Biology
Molecular Genetics Nucleic Acids Pathogenesis Proteins and Macromolecules
Proteomics Recombinant DNA Respiratory System Salmonella
Urogenital System
 
Research Projects
Project title High throughput analysis of enterobacterial invasion
Summary Enterobacterial outer membrane proteins such as Hek, PagN and Tia (also known as PATH proteins) utilise mammalian, cell surface, heparinated-molecules to accomplish invasion of these cells. What is the molecular identity of these mammalian molecules and what signalling events are triggered in epithelial cells that facilitate bacterial entry mediated by PATH proteins? Furthermore, what is the nature of the interaction between the bacterial ligands and their receptors; specifically – what amino acid sequences are required in PATH proteins for epithelial invasion? To answer these questions the following experiments are underway 1. To adopt and adapt high-throughput fluorescent microscopy (Cellomics) in the analysis of microbial invasion of human epithelial cells. 2. To define the class of HSPG that PATH proteins bind to. 3. Define, at a molecular level, the sequences within PATH proteins that are required for HSPG-binding.
Funding Agency SFI
Programme
Type of Project
Date from 1/10/10
Date to 1/10/14
Person Months


Project title E. coli sepsis; better treatment options using genomics
Summary Hypothesis 1 We have identified genes in pathogenic E. coli that protect the bacteria from serum killing in vivo. We hypothesize that these genes will be important in clinically-significant E. coli bloodstream infections in patients. Hypothesis 2 We hypothesize that E. coli bloodstream isolates are becoming increasingly more virulent and resistant to antimicrobials. Aims The aim of this proposal is to measure gene expression of pathogenic E. coli from patient blood samples. We will ascertain if the induction of particular bacterial genes during infection is clinically significant. In parallel with this approach we will continue to gather large amounts of genotypic information on each bacterial isolate using microarray technologies. Objectives The main objectives will be to; • Measure the transcriptional responses of pathogenic E. coli exposed to complement-deficient serum. • Refine and enhance the virulence and resistance microarray. • Establish the SCOTS methodology in vitro • Apply SCOTS to patient samples • Determine if there is a correlation between the expression of protective genes in E. coli and clinical outcome.
Funding Agency HRB
Programme
Type of Project
Date from 1/1/11
Date to 1/6/14
Person Months


Project title E. coli sepsis; better treatment options using genomics
Summary Hypothesis 1 We have identified genes in pathogenic E. coli that protect the bacteria from serum killing in vivo. We hypothesize that these genes will be important in clinically-significant E. coli bloodstream infections in patients. Hypothesis 2 We hypothesize that E. coli bloodstream isolates are becoming increasingly more virulent and resistant to antimicrobials. Aims The aim of this proposal is to measure gene expression of pathogenic E. coli from patient blood samples. We will ascertain if the induction of particular bacterial genes during infection is clinically significant. In parallel with this approach we will continue to gather large amounts of genotypic information on each bacterial isolate using microarray technologies. Objectives The main objectives will be to; • Measure the transcriptional responses of pathogenic E. coli exposed to complement-deficient serum. • Refine and enhance the virulence and resistance microarray. • Establish the SCOTS methodology in vitro • Apply SCOTS to patient samples • Determine if there is a correlation between the expression of protective genes in E. coli and clinical outcome.
Funding Agency HRB
Programme
Type of Project
Date from 1/1/11
Date to 1/6/14
Person Months


 
Publications and Other Research Outputs
Peer Reviewed
Miajlovic H, Cooke NM, Moran GP, Rogers TR, Smith SG., Response of Extraintestinal Pathogenic Escherichia coli to Human Serum Reveals a Protective Role for Rcs-Regulated Exopolysaccharide Colanic Acid., Infect Immun, 2014, p298 - 205
Sanjay H. Chotirmall, Stephen G. Smith, Cedric Gunaratnam, Sonya Cosgrove, Borislav D. Dimitrov, Shane J. O'Neill, Brian J. Harvey, Catherine M. Greene, Noel G. McElvaney, , Effect of Estrogen on Pseudomonas Mucoidy and Exacerbations in Cystic Fibrosis, The New England Journal of Medicine, 366, 2012, p1978 - 1986
Greene CM, Carroll TP, Smith SG, Taggart CC, Devaney J, O’Neill SJ & McElvaney NG , TLR-induced inflammation in Cystic Fibrosis Epithelial Cells , Journal of Immunology, 174, 2005, p1638 - 1646
URL
Taggart CC, Greene CM, Smith SG, Levine RL, McCray PB Jr, O'Neill S & McElvaney NG , Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. , Journal of Immunology, 171, 2003, p931 - 937
URL
Regulation of virulence gene expression in bacterial pathogens in, editor(s)EA Groisman , Principles of Bacterial Pathogenesis, New York, Academic Press, 2001, [Dorman CJ & Smith SGJ ]
More Publications and Other Research Outputs >>>
 

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Last Updated:24-APR-2014