Robins-Browne Laboratory
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Include: Research Interests | Collaborative Research | Funding | Some recent findings - Enteropathogenic Escherichia coli - Enterotoxigenic Escherichia coli | Laboratory Staff | Selected Recent Publications
Research Interests
Figure 1. Destruction of microvilli on the surface
of the intestine by enteropathogenic E. coli (arrow).
The major focus of our research is the molecular pathogenesis of bacterial infections. We use molecular biological, genetic, proteomic, and cell biological approaches to gain insight into the processes by which pathogenic bacteria interact with their hosts. The bacteria we use as model pathogens for this research are mainly diarrhoea-causing strains of E. coli, in particular enteropathogenic E. coli. We also work with group A streptococci, Streptococcus pneumoniae and Pseudomonas aeruginosa
The principal goals of our work are to improve understanding of the strategies that bacteria employ to cause disease, and to use this information to improve current methods to diagnose, treat and prevent bacterial infections.
Collaborative research
Figure 2. Photomicrographs showing that
enteropathogenic E. coli (arrow) which attach to
epithelial cells (left) cause actin to accumulate at
the site of attachment (right).
In addition to our laboratories in the Department of Microbiology and Immunology (where we have a number of collaborators), we have laboratories at the Murdoch Childrens Research Institute (www.mcri.edu.au) located at the Royal Children's Hospital (www.rch.org.au). Here we undertake collaborative research with a number of hospital-based scientists and clinicians on topics as diverse as “Immunity to tuberculosis” (with Professor Nigel Curtis); “Detection of carriers of Streptococcus pneumoniae” (with Professor Kim Mulholland, Dr Catherine Satzke and others); “The use of lactobacilli to modulate immune responses” (with Assoc Prof Mimi Tang) and “The early detection of infection in children with cystic fibrosis” (with Professor Colin Robertson, Assoc Prof Sarath Ranganathan, Dr Emily Hart and other members of the AREST CF team ( http://www.arestcf.org). We also work closely with clinicians at the Victorian Eye and Ear Hospital (Professor Stephen O'Leary) on the pathogenesis and prevention of otitis media and with scientists at Monash University (Professor Trevor Lithgow) on protein secretion by bacteria, the Menzies Institute (Professor Jonathan Carapetis) on the causes of acute diarrhoea in hospitalised children. We have collaborations with commercial organisations, including Immuron Ltd (http://www.immuron.com), whose major interest is the development of passive immunisation against infection, and with Polyactiva (http://www.bionicear.org/research/Polyactiva.html) on their drug delivery program. We also collaborate with an international team of scientists on The Global Enterics Multi-Center Study ( http://medschool.umaryland.edu/GEMS/default.asp), which is investigating the causes and effects of acute infectious gastroenteritis in young children in less-developed countries.
Funding
Funding for our research comes mainly from grants awarded by the Australian National Health & Medical Research Council and the Australian Research Council. We also have research contracts with the University of Maryland, Polyactiva, the Gates Grand Challenges in Global Health Fund, Water Quality Research Australia and Cochlear Limited.
Some recent findings
Enteropathogenic Escherichia coli
Enteropathogenic E. coli (EPEC) is an important cause of acute diarrhoea in children. We have shown that EPEC is also an important cause of persistent diarrhoea in children attending hospital in Melbourne. As part of our work on the pathogenesis of infections caused by EPEC, we have identified a protein export pathway in EPEC that is identical to that used by enterotoxigenic strains of E. coli to secrete heat-labile enterotoxin. Although EPEC secretes no known toxins, it appears to require the protein secretory pathway to produce biofilms and to persist in the gastrointestinal tract. We have also identified novel gene regulatory systems in diarrhoea-associated E. coli and related bacteria that are essential for virulence. One of these systems responds to bicarbonate ions, which are abundant in the gut.
Enterotoxigenic Escherichia coli
Figure 3. Ribbon diagram of the heat-stable
enterotoxin of enterotoxigenic E. coli (Ozaki et al.
JBC 1991; 266: 5934-41) modelled using the
software MacPyMol.
Enterotoxigenic E. coli (ETEC) is a leading cause of severe diarrhoea in children in less-developed countries and in travellers to those countries. Although the virulence determinants of ETEC are well understood, there is no effective vaccine for ETEC-associated diarrhoea. One of the reasons for this is that the heat-stable enterotoxin (ST), which is a major virulence determinants of ETEC, that is produced by around 80% of strains, is not antigenic, and does not elicit any type of immune response, even after natural infection. Together with our Departmental collaborators, Prof David Jackson and Dr Weiguang Zeng, we have constructed and evaluated a synthetic ST vaccine, which incorporates a T-helper epitope and a self-adjuvanting component. Although this vaccine elicits protective antibodies to ST in animals, we are currently refining it to increase its efficacy and broaden its specificity. We are also developing models of infection with ETEC to evaluate the ability of the vaccines we develop to protect against diarrhoea caused by ST-producing strains of ETEC.
Laboratory Staff
Laboratory Head and Head of Department
Professor Roy Robins-Browne
Email:r.browne@unimelb.edu.au
Current laboratory staff
Louise Adams, Research assistant
Thakshila Amarasena, Technical assistant
Kristy Azzopardi, Research assistant
Dr Jennifer Bender, Visiting postdoctoral scientist
Vicki Bennett-Wood, Research assistant
Catherine Cheng, Research assistant
Susie Germano, Research assistant
Dianna Hocking, Research assistant<
Danijela Krmek, Technical assistant
Dr Judyta Praszkier, Postdoctoral scientist
Dr Yogitha Srikhanta, Postdoctoral scientist
Dr Marija Tauschek, Postdoctoral scientist
Current students
Aimee Tan, PhD student
Dr Vanessa Clifford*, PhD student
Ellen Higginson, PhD student
Carla Hodson, BSc Hons student
Dr Mary John*, PhD student
Joel Selkrig*, PhD student
Dr Marc Tebruegge*, PhD student
† based off campus
Selected Recent Publications
List of Publications prior to 2009
- Otto W, Najnigier B, Stelmasiak T, Robins Browne RM. Randomised control trials using a tablet formulation of hyperimmune bovine colostrum to prevent diarrhoea caused by enterotoxigenic Escherichia coli in volunteers. Scand J Gastroenterol 2011; in press.
- Robins-Browne RM. Yersinia. In: Doyle MP, Buchanan RL, eds. Food microbiology: fundamentals and frontiers, 4th edition. Washington, DC: American Society for Microbiology, 2011; in press.
- Boyle RJ, Ismail IH, Licciardi PV, Robins-Browne RM, Mah L-J, Axelrad C, Moore S, Donath S, Carlin JB, Lahtinen SJ, Tang MLK. Lactobacillus GG treatment during pregnancy for the prevention of eczema: a randomized controlled trial. Allergy 2011; in press.
- Zeng W, Horrocks KJ, Robevska G, Wong CY, Azzopardi K, Tauschek M, Robins-Browne RM, Jackson DC. A modular approach to assembly of totally synthetic self-adjuvanting lipopeptide-based vaccines allows conformational epitope building. J Biol Chem 2011; 286: 12944-12951.
- Yang J, Tauschek M, Robins-Browne RM. Control of bacterial virulence by AraC-like regulators that respond to chemical signals. Trends Microbiol 2011; 19: 128-135.
- Tan A, Yang J, Tauschek M, Praszkier J, Robins-Browne RM. Autogenous transcriptional regulation of the regA gene encoding an AraC like/essential virulence regulator in Citrobacter rodentium. J Bacteriol 2011; 193: 1777-1782.
- Satzke C, Ortika BD, Oftadeh S, Russell FM, Robins-Browne RM, Mulholland EK, Gilbert GL. Molecular epidemiology of Streptococcus pneumoniae serogroup 6 isolates from Fijian children, including newly identified serotypes 6C and 6D. J Clin Microbiol 2010; 48: 4298-4300.
- Tauschek M, Yang J, Hocking D, Azzopardi K, Tan A, Hart E, Praszkier J, Robins-Browne RM. Transcriptional analysis of the grlRA virulence operon from Citrobacter rodentium. J Bacteriol 2010; 192: 3722-3734.
- Newton HJ, Pearson JS, Badea L, Kelly M, Lucas M, Holloway G, M Wagstaff KM, Dunstone MA, Sloan J, Whisstock JC, Kaper JB, Robins-Browne RM, Jans DA, Frankel G, Phillips AD, Coulson BS, Hartland EL. The type III effectors NleE and NleB from enteropathogenic E. coli and OspZ from Shigella block nuclear translocation of NF-ΚB p65. PLoS Pathog 2010; 6(5): e1000898.
- Hart E, Azzopardi K, Taing H, Graichen F, Jeffery J, Mayadunne R, Wickramaratna M, O'Shea M, Nijagal B, Watkinson R, O'Leary S, Finnin B, Tait R, Robins-Browne R. Efficacy of antimicrobial polymer coatings in an animal model of bacterial infection associated with foreign body implants. J Antimicrob Chemother 2010; 65: 974-980.
- Yang J, Tauschek M, Hart E, Hartland EL, Robins-Browne RM. Virulence regulation in Citrobacter rodentium: the art of timing. Microb Biotechnol 2010; 3: 259-268.
- Gorrell RJ, Robins-Browne RM. Antibody-mediated protection against infection with Helicobacter pylori in a suckling mouse model of passive immunity. Infect Immun 2009; 77: 5116-5129.
- Yang J, Dogovski C, Hocking D, Tauschek M, Perugini M, Robins-Browne RM. Bicarbonate-mediated stimulation of RegA, the global virulence regulator from Citrobacter rodentium. J Mol Biol 2009; 394: 591-599.
- Hart E, Tauschek M, Bennett-Wood V, Hartland EL, Robins-Browne RM. Rabbit-specific fimbriae, Ral, alter the patterns of in vitro adherence and intestinal colonisation of rabbits by human-specific enteropathogenic E. coli. Microbes Infect 2009; 11: 803-810.
- Cheng C, Tennant SM, Azzopardi KI, Bennett-Wood V, Hartland EL, Robins-Browne RM, Tauschek M. Contribution of the pst-phoU operon to cell adherence by atypical enteropathogenic Escherichia coli and the virulence of Citrobacter rodentium. Infect Immun 2009; 77: 1936-1944.
- Tennant SM, Tauschek M, Azzopardi K, Bigham A, Bennett-Wood V, Hartland EL, Qi W, Whittam TS, Robins-Browne RM. Characterisation of atypical enteropathogenic E. coli strains of clinical origin. BMC Microbiol 2009; 9: 117.
- Lahtinen SJ, Boyle RJ, Kivivuori S, Oppedisano F, Smith KR, Robins-Browne R, Salminen SJ, Tang MLK. Prenatal probiotic administration can influence Bifidobacterium microbiota development in infants at high risk of allergy. J Allergy Clin Immunol 2009; 123: 499-501.
- Bryant PA, Smyth GK, Robins-Browne R, Curtis N. Detection of gene expression in an individual cell type within a cell mixture using microarray analysis. PLoS ONE 2009; 4: e4427.
- Newton HJ, Sloan J, Bulach DM, Seemann T, Allison CC, Tauschek M, Robins-Browne RM, Paton JC, Whittam TS, Paton AW, Hartland EL. The emergence of LEE-negative Shiga toxin producing Escherichia coli: clonal structure and acquisition of the large virulence plasmid, pO113. Emerg Infect Dis 2009; 15: 372-380.
- Ritz N, Tebruegge M, Connell TG, Robins-Browne R, Curtis N. Susceptibility of BCG vaccine strains to antituberculous antibiotics. Antimicrob Ag Chemother 2009; 53: 316-318.