Personal profile

Overview

Interactions between pathogens and the host. Research in my laboratory is focused on the interactions between bacteria and their human hosts. Pathogenic bacteria are responsible for a number of life threatening infections of man and have devised strategies to overcome the host host’s defences. Specifically, they produce “virulence factors” that manipulate and re-program the ability of the host to combat the infection and it is the success or failure of this battle that will decide the outcome of the infection. In addition to looking at specific interactions between the pathogen and the host we are also looking at global changes that occur in the host as a consequence of the infection. In particular, we are looking at the microflora of the human gut and studying how infection both acute and chronic may alter the human gut flora and what are the consequences to the health of the host. We are studying two bacterial pathogens Escherichia coli responsible for urinary tract infections and Listeria monocytogenes a serious food borne pathogen. In addition, we are studying the effects of infection by the parasitic worm Trichuris muris on the host gut microflora.

Biography

Professor Ian Roberts - Molecular Microbiology Research Group, Faculty of Life Sciences. 1981-BSc. Biological Sciences University of Leicester, 1984-PhD (Genetics) University of Birmingham. In 1986 I was appointed to a Lecturship in the Department of MIcrobiology at the University of Leicester and was promoted to Senior Lecturer in 1993. In 1995 I was awarded a fellowship from the Lister Institute of Preventive Medicine and was appointed to the Chair in Microbiology at Manchester in the same year. During my time at Manchester I have been a Divisonal Head, Research Dean (2001-2005 and 2012-2016) and I am now currently a member of the Lydia Becker Institute of Immunology and Inflammation. I  served on the BBSRC Student ships and Fellowships Panel (2002-2013) being Chair between (2009-2013) as well as serving on a number of national and international funding committees. I am an Editor of Future Microbiology. In 1994 I was awarded both the Fleming Lectureship. and the Pierce Award. The Fleming Lectureship is made annually by the Society for General Microbiology in recognition of outstanding research by a microbiologist (under 35 years of age) within the UK. While the W. H. Pierce award is made annually by the Society for Applied Bacteriology in recognition of outstanding research in the field of bacteriology. I am currently the Honorary Tresurer of the Microbiology Society (2018-2021).

Research interests

In the laboratory there are three major projects.

1). The role of capsular polysaccharides in extra-intestinal infections caused by Escherichia coli.

Escherichia coli cause a number of extra-intestinal infections such as urinary tract infections, blood poisoning (septicemia) and meningitis in new born children. A key virulence factor is the expression of a polysaccharide capsule that coats the outside of the E. coli and protects it from host defences. The research has two broad objectives-first to understand how capsular polysaccharide expression is regulated in E. coli during an infection. This research will not only elucidate at the molecular level the mechanisms by which the genes encoding for capsular polysaccharide synthesis are regulated but also shed light on the role of the capsular polysaccharide during different stages of an infection. This project primarily uses molecular genetic approaches. The second objective is to understand how capsular polysaccharides are transported out of the bacterial cell. The export of large polysaccharide molecules out of the cell represents a fascinating challenge to the bacterium. In addition, understanding how this process is mediated will allow the synthesis of transport inhibitors that could potentially be used to treat infections. Moreover, we should be able to exploit the transport process to export polysaccharides of biomedical importance that have been engineered in Escherichia coli. This project combines molecular biology and structural biology.

2). The growth of the food borne pathogen Listeria monocytogenes inside the host.

Listeria monocytogenes is a food borne pathogen responsible fro a number of infections including intra-uterine infections of the unborn foetus. A key characteristic of L. monocytogenes is its ability to grow inside host cells, a process which represents a nutritional challenge to the bacterium. The intracellular life cycle of L. monocytogenes has been well studied. In my laboratory we are studying the ability of intracellular L. monocytogenes to acquire zinc a key element for growth the availability of which tightly regulated within the host cell. Recently my group has initiated research on the growth of L. monocytogenes in the intestine prior to invasion. Both project involve combining molecular, genetic and biochemical approaches with tissue culture and cell biology.

3). Studies on the gut microbiota during long-term chronic parasitic infections.

The microbiota of the large intestine play key roles in the health of the host including maturation of the host immune system, digestion of dietary molecules, prevention of infection and generation of important signaling molecules to the host. Changes in the host microbiota have been implicated in a number of disorders including obesity, cancer and behavior. In my laboratory in collaboration with the Grencis laboratory we are looking at how the microbiota of the host is affected by chronic parasite infection (Trichuris muris) and crucially the implications to the host of such changes. The project involves metagenomics, bioinformatics, molecular microbiology and metabolomics.

Opportunities

Regulation of intestinal immune responses to commensal bacteria by innate lymphoid cells

Commensal bacteria present in the gastrointestinal tract provide beneficial roles for the host, such as supporting nutrient metabolism. In order to peacefully co-exist with the intestinal microflora the immune system has evolved multiple mechanisms through which it suppresses inflammatory immune responses against commensal bacteria, which together generate a tolerogenic environment. A breakdown in this tolerance can result in the onset of chronic inflammatory disorders such as Inflammatory Bowel Disease (and colon cancer), hepatitis, and rheumatoid arthritis.

Innate lymphoid cells (ILCs) play key roles in mediating intestinal immune homeostasis and maintaining healthy host-commensal bacteria interactions via the production of cytokines, interactions with other tissue-resident immune cell populations and the orchestration of local immune responses. In particular, recent studies have demonstrated that group 3 innate lymphoid cells are able to prevent intestinal inflammation by controlling the activation of commensal bacteria-specific inflammatory T cells in an antigen-specific manner (Hepworth et al Nature 2013, Science 2015).

This project will investigate i) how ILCs interact with intestinal immune cells to regulate responses to commensal bacteria ii) which bacterial species preferentially drive intestinal inflammation following disruption of ILC regulatory function(s) and iii) the specificity of ILC-regulation of inflammatory responses.

The project will utilize a range of approaches including the use of animal models, immunological techniques (flow cytometry, ELISA), molecular biology (PCR, sequencing) and microbiological methods to investigate interactions between the host immune system and the commensal microbiota in the context of health and disease.

The student will my join my laboratory located within the world-class Faculty of Life Sciences at the University of Manchester and will have access to a wide range of facilities and expertise across the faculty.

 

  • Hooper LV, Littman DR and MacPherson AJ. Interactions between the microbiota and the immune system. Science 2012 June 8; 336(6086)
  • Belkaid Y and Hand TW. Role of the microbiota in immunity and inflammation. Cell 2014 Mar 27; 157(1)
  • Hepworth MR et al Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells Science 2015 May 29; 348(6238)
  • Hepworth MR et al Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria Nature 2013 Jun 6; 498(7452)
  • Palm NW et al Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease Cell 2014 Aug 28; 158(5)

 

Studies on food borne pathogens of man- how does Listeria monocytogenes survive inside the host intestine?

Listeria monocytogenes is a facultative intracellular Gram positive bacterium and the aetiological agent of Listeriosis a serious food borne disease. In contrast to other food borne infections, Listeriosis has high mortality rates (20-30%) despite antibiotic intervention. Infection can be perinatal where disease may manifest as listeric abortion, stillbirth or late-onset neonatal meningitis. In contrast, listeric infection in non-pregnant individuals usually affects the central nervous system manifesting as either meningitis or meningoencephalitis and atypically as endocarditis and pneumonia. In the case of immunocompromised patients, L. monocytogenes is the most commonly encountered form of bacterial meningitis with mortality rates as high as 60%. The incidence of listeriosis is increasing in the elderly population and with an expanding aged population the control of listeriosis remains an emerging priority. The principal mode of transmission of L. monocytogenes to humans is the ingestion of contaminated food with unpasteurized diary products, uncooked vegetables and chilled processed meat products being the main sources of infection. There have been a number of well-documented cases of food borne Listeriosis and globally, Listeriosis accounts for 30% of all fatalities as a consequence of food borne infection. As such L. monocytogenes represents a serious food-borne pathogen, which based on changing demographics and life style will pose an increasing risk. The project aims to use molecular microbial genetics, cell biology and metabolomics to study the survival and adaptation of  L. monocytogenes to its transit through the small intestine prior to invasion.

 

  • Corbett, D., Schuler, S., Glenn, S.,  Andrew, P. W.,  Cavet, J. S., Roberts, I. S. (2011) The combined actions of the copper-responsive repressor CsoR and copper-metallochaperone CopZ modulate CopA-mediated copper efflux in the intracellular pathogen Listeria monocytogenes. Mol. Microbiol.  81:457-472.
  • Corbett, D., Wang, J., Schuler, S., Lopez-Castejon, G., Glenn, S., Brough, D., Andrew, P.W., Cavet, J.S., Roberts, I.S. (2012) Two Zinc Uptake Systems Contribute to the Full Virulence of Listeria monocytogenes During Growth in vitro and in vivo. Infect Immun. 80:14-21.
  • Lopez-Castejon G, Corbett D, Goldrick M, Roberts IS, Brough D, (2012) Inhibition of Calpain blocks the phagosomal escape of Listeria monocytogenes PLoS ONE 7:e35936
  • Corbett, D, Goldrick, M., Fernandes V. E., Davidge, K., Poole R. K., Andrew P. W., Cavet J., Roberts I. S. (2017).Listeria monocytogenes has both a bd-type and an aa3 -type terminal oxidase which allow growth in different oxygen levels and both are important in infection.(2017). Infect. Immun. 85:e00354-17 doi: 10.1128/IAI.00354-17

Studies on pathogenic Escherichia coli responsible for extra-intestinal infections of man

Escherichia coli are responsible for a number of serious extra-intestinal infections of man. These range from urinary tract infections through to septicaemia and meningitis. Often these E. coli are resistant to many antibiotics. The expression of cell surface structures such as the polysaccharide capsule or K antigen, is important during infection and growth in the host. These structures are important in mediating interactions between the pathogen and its immediate environment in the host. Specifically the expression of a K antigen is important in protecting the E. coli from killing by the host’s innate immune response. The project will focus in understanding how expression of the polysaccharide capsule is mediated during growth on and in host uroepithelial cells following invasion. The project will use state of the art genomics methodologies such as RNAseq as well as advanced live cell imaging.

  

  • Corbett, D., Roberts, IS. (2009). The role of microbial polysaccharides in host-pathogen interaction. F1000 Biology Reports 2009, 1:30 (doi: 10.3410/B1-30)
  • Hafez, M., Hayes, K., Goldrick, M., Warhurst, G., Grencis, R., Roberts, I. S. (2009). The K5 capsule of Escherichia coli strain Nissle 1917 is important in mediating interactions with intestinal epithelial cells and chemokine induction. Infect. Immun. 77: 2995-3003.
  • Hafez, M., Hayes, K., Goldrick, M., Grencis, R., Roberts, I. S. (2010). The K5 capsule of Escherichia coli strain Nissle 1917 is important in stimulating expression of TLR5, CD14, MyD88 and TRIF together with the induction of IL-8 expression via the MAPK-pathway in epithelial cells. Infect. Immun. 78:2153-2162
  • Thompson, J. E., Pourhossein, M.,  Waterhouse, A., Hudson, T., Goldrick, M., Derrick, J. P., Roberts. I. S. (2010). The K5 lyase KflA combines a viral tail spike structure with a bacterial lyase mechanism. J. Biol. Chem. 285: 23963-23969.
  • King, J. E., Aal Owaif H. A.,Jia, J.,Roberts, I. S. (2015). Phenotypic Heterogeneity in Expression of the K1 Polysaccharide Capsule of Uropathogenic Escherichia coliand its Down Regulation during Growth in Urine. Infect Immun.83:2605-13 

  • Jia, J., King, J. E., Goldrick, M., Aldawood, E., Roberts I. S. (2017).Three tandem promoters, together with IHF, regulate growth phase dependent expression of the Escherichia coli kpscapsule gene cluster. Sci. Reports 7:17924 doi:10.1038/s41598-017-17891-0

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Research Beacons, Institutes and Platforms

  • Digital Futures
  • Lydia Becker Institute
  • Christabel Pankhurst Institute

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