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Sinead Corr - Research Page

Research Activities – Professor S. Corr, Assistant Professor in Microbiology

Host-Microbe Interface & Gut Immunity

Dr Sinéad Corr, PhD
SFI SIRG Fellow
Email: corrsc@tcd.ie
Phone: +353-1-896 1195

https://www.tcd.ie/genetics-microbiology/assets/pdf/Corr.pdf


Research Interests

Overview My laboratory focusses primarily on the host-microbe interface within the gastrointestinal (GI) tract, in particular modulation of intestinal immunity by the gut microbiota. We use molecular based approaches combined with animal models and clinical samples to understand the molecular mechanisms which govern the interplay between the gut microbiota and the host organism, specifically with the intestinal epithelial barrier and innate immunity. The subsequent maintenance of health or development of infectious or inflammatory disease as a result of this interplay is of particular interest. Gastroenteritis, including bacterial infectious diseases, are a major cause of morbidity and mortality worldwide, while inflammatory bowel diseases (IBDs) affect over 2 million people in Europe. An important aspect of our work is to characterize the host mechanisms which mediate gut health in response to infectious and resident microbes and to determine how the presence of the commensal microbiota can influence intestinal immunity, giving rise to either homeostasis or disease. The key focus of this work is to enable strategic manipulation of intestinal immunity and the gut microbiota with the ultimate goal of reducing the severity of intestinal infectious and inflammatory diseases.

What we work on

Regulation of the Intestinal epithelial barrier & immunity. The epithelial cells lining the GI tract form a barrier between the body and the luminal environment which not only contains nutrients and commensal microbiota, but also potentially harmful microorganisms and toxins. This epithelial barrier is pivotal to intestinal health or disease, with loss of barrier integrity or “leaky gut” being implicated in a range of diseases including infectious enterocolitis and IBD. Epithelial cells express pattern recognition receptors (PRRs) which orchestrate mucosal defences during infection and respond to gut commensals to maintain intestinal wellbeing. As a result, the GI epithelium is a crucial site of immune regulation and the integrity of this barrier determines health or development of disease. We use in vitro and in vivo methods to investigate the mechanisms which control the functional integrity of the gut epithelial barrier, in particular the role played by intestinal epithelial tight junctions which determine barrier permeability and leakiness, and have been implicated in arrange of inflammatory disorders.

Fig1

Intestinal Occludin Corr. et al 2013
http://www.ncbi.nlm.nih.gov/pubmed/2361205

Fig2

3D image of ZO-1 in intestinal epithelium. Corr et al 2013
http://www.ncbi.nlm.nih.gov/pubmed/23612054

The Gut Microbiota Research in my lab heavily focusses on the host-microbiota dialogue, investigating the signalling interactions between the host and its microbiota which mediate immune-inflammatory responses. The relationship between the host and its gut microbiota is largely a beneficial one, with members of the microbiota being instrumental to human physiology and wellbeing. Microbial presence and activity influences the function of intestinal defences, and has key roles in improving digestive function, in the reduction of chronic inflammation, and in hastening recovery from intestinal disease. However this relationship can become detrimental due to disturbances including alterations in diet and antibiotic use, and the resulting microbial dysbiosis has been linked to infection, IBD, diabetes and obesity. Using in vivo based methods combined with Next-Generation Sequencing we hope to decipher to what extent the microbiota can modulate the intestinal barrier and inflammation, and how beneficial members of the microbiota, termed “probiotics”, can be used to therapeutically manipulate gut immunity or to directly inhibit infection by bacterial pathogens. Translation of our research and the development of novel therapies for the treatment of microbiome-associated inflammatory conditions like IBD is an integral part of our work.

Fig3

Mice infected with luciferase-tagged Listeria. Corr et al 2007
http://www.ncbi.nlm.nih.gov/pubmed/17456596

 

 

 

 

 

 

 

Bacterial Gastroenteritis To date, work in has focussed on understanding the intestinal phase of infection with gut pathogens, specifically Listeria monocytogenes   and  Salmonella Typhimurium. We are interested in the characterization of new bacterial virulence factors involved in bacterial entry into host cells and cell-to-cell spread, and in deciphering the host mechanisms to combat infection, playing a critical role in the outcome of infectious disease. Furthermore, the strategies evolved by bacteria to subvert these host defence mechanisms and immune responses enabling spread within the host in a research focus.

Luciferase-tagged Listeria. Bron et al 2006
http://www.ncbi.nlm.nih.gov/pubmed/16597994

TEM of intestinal M-cell. Corr et al 2006
http://www.ncbi.nlm.nih.gov/pubmed/17049432

  • Research Personnel

Postdoctoral Research Fellows:
Dr Elaine Dempsey

Postgraduate Students:
Daniel Johnston
Michelle Williams
Amy O'Callaghan

  • Collaborators

Prof. Luke O'Neill, School of Biochemistry & Immunology, Trinity College, Ireland.

Prof. Padraic Fallon, School of Medicine, Trinity College, Ireland.

Prof. Fergus Shanahan, Alimentary Pharmabiotic Centre, University College Cork, Ireland.

Prof. Colin Hill, Alimentary Pharmabiotic Centre, University College Cork, Ireland.

Prof. Pascale Cossart, Unité des Interactions Bactéries-Cellules, Institut Pasteur, France.

Prof. Olivier Dussurget, Unité des Interactions Bactéries-Cellules, Institut Pasteur, France.

Prof. Kate Fitzgerald, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, USA.

Prof. Satya Dandekar, Dept. of Medical Microbiology and Immunology, University of California, Davis, USA.

  • Financial Support

Science Foundation Ireland Starting Investigator Research Grant

BROAD Medical Research Program & Crohn’s and Colitis Foundation America

  • Interested in working with us?

We are always interested in recruiting talented people to the lab and in supporting applications for personal PhD and postdoctoral fellowships. For further information please contact Sinéad ( corrsc@tcd.ie )

Selected Publications

Johnston, D.G.W., Williams, M.A., Thaiss, C.A., Cabrera-Rubio, R., Raverdeau, M., McEntee, C., Cotter, P., Elinav, E., O’Neill, L.A.J. and Corr, S.C. Loss of microRNA-21 Influences the Gut Microbiota Causing Reduced Susceptibility in a Murine Model of Colitis. Journal of Crohn's and Colitis, 2018, jjy038, https://doi.org/10.1093/ecco-jcc/jjy038

Johnston D.G.W., Kearney J., Zasłona Z., Williams M.A., O'Neill L.A., Corr S.C. MicroRNA-21 Limits Uptake of Listeria monocytogenes by Macrophages to Reduce the Intracellular Niche and Control Infection. Front. Cell. Infect. Microbiol. 2017 May 23; 7:201. doi: 10.3389/fcimb.2017.00201.

Johnston, D.G. and Corr, S.C. TLR signalling and intestinal epithelial barrier function in vivo. Springer protocols, Methods of Molecular Biology 2016, 1390:287-300

Aviello, G., Corr, S.C., Johnston, D.G., O’Neill, L.A. and Fallon, P.G. MyD88 adaptor-like (Mal) regulates intestinal homeostasis and colitis-associated colorectal cancer in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2014, 306(9):G769-78

Corr , S.C., Palsson-McDermott, E.M, Grishina, I., Barry, S.P., Aviello, G., Bernard, N.J., Casey, P.G., Ward, J.B., Keely, S.J., Dandekar, S., Fallon, P.G. and O’Neill, L.A. MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C. Mucosal Immunol. 2014, 7(1):57-67.

Tannahill, G.M., Curtis, A.M., Adamik, J., Palsson-McDermott, E.M., McGettrick, A.F., Goel, G., Frezza, C., Bernard, N.J., Kelly, B., Foley, N.H., Zheng, L., Gardet, A., Tong, Z., Jany, S.S., Corr, S.C., Haneklaus, M., Caffrey, B.E., Pierce, K., Walmsley, S., Beasley, F.C., Cummins, E., Clish, C., Nizet, V., Whyte, M., Taylor, C.T., Lin, H., Masters, S.L., Gottlieb, E., Kelly, V., Clish, C., Auron, P.E. Xavier, R.J., O’Neill, L.A. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 2013, 496(7444):238-42.

Corr , S.C., Aubry, C., Wienerroither, S., Goulard, C., Jones, R., Jamieson, A., Decker, T., O’Neill, L.A., Dussurget, O. and Cossart, P. Both TLR2 and TRIF contribute to interferon-β production during Listeria infection. PloS One 2012, 7(3):e33299

Corr , S.C. and O’Neill, L.A. Genetic Variation in TLR signalling and the risk of inflammatory and immune diseases. J. Innate Immun. 2009, 1(4):350-357.

Corr, S.C., Li, Y., Riedel, C.U., O’Toole, P.W., Hill, C. and Gahan, C.G. From the Cover: Bacteriocin production as a mechanism for the anti-infective activity of Lactobacillus salivarius UCC118. Proc. Natl. Acad. Sci. U.S.A. 2007 104(18):7617-7621.

 


Last updated 23 April 2018 by Microbiology (Email).