Gastrointestinal Infection and Inflammation

Location: Department of Microbiology, Rooms 129 (laboratory)/130 (office)
Telephone: 61 (03) 9905 4842 (office)/54836 (laboratory)
Facsimile: 61 (03) 9905 4811.

Research Group Head:

Dr Richard L. Ferrero B.App.Sc. (NSWIT), Ph.D. (UNSW) Richard.Ferrero@med.monash.edu.au

Research Staff:

Postdoctoral fellow: Dr Maria Kaparakis B.Sci., Ph.D. (Uni Melb) Maria.Kaparakis@med.monash.edu.au
Technical Assistant: Abdulgader Karrar Abdul.Karrar@med.monash.edu.au
PhD Student: Cody Allison Cody.Allison@med.monash.edu.au
Honours Students: Melanie Hutton Melanie.Hutton@med.monash.edu.au
Shoshanah Longmuir Shosh.Longmuir@med.monash.edu.au
Hazel Yuet Mei Tye Hazel.tye@med.monash.edu.au
Research Assistant (part-time from 07/2007): Alexandra Grubman Alex.Grubman@med.monash.edu.au

Research interests of the group

Helicobacter spp colonise the gastrointestinal tracts of a diverse array of mammals, including human and animal hosts. Several members of the Helicobacter genus are associated with various types of inflammatory conditions, including gastritis and colitis. The best characterised of these species is Helicobacter pylori , the aetiological agent in peptic ulcer disease and gastric carcinogenesis in humans. The direct interaction of H. pylori bacteria with the external surfaces of gastric epithelial cells (Fig. 1) results in a variety of cellular responses including increased cell motility, cytoskeletal rearrangements and the induction of pro-inflammatory signalling.

The laboratory uses H. pylori as an infection model to study host-pathogen interactions at mucosal surfaces. Specifically, we have been investigating the role that innate immune molecules play in host recognition of this bacterial pathogen. Among the key findings of our previous work was the elucidation of the role of the cytosolic pathogen recognition molecule, Nod1, in epithelial cell responses and host defence against H. pylori strains harbouring a type IV secretion system (T4SS) (Fig. 2). Nod1 recognises cell wall peptidoglycan that is delivered to host cells via the H. pylori T4SS (Fig. 3).

Examples of the research topics being investigated by the group:

1. Nod1-dependent regulation of antimicrobial peptide synthesis in epithelial cells.
2. Role of Nod1 in the development of adaptive immune responses to H. pylori infection.
3. Cell entry and intracellular trafficking of H. pylori peptidoglycan.
4. Generalised mechanisms whereby extracellular pathogens induce Nod1 signalling in host cells.
5. Identification and characterisation of novel virulence factors required for H. pylori infection.

Fig. 1 H. pylori bacteria expressing green fluorescent protein can be seen interacting with gastric epithelial cells. (M. Hutton)

Fig. 2 H. pylori induces pro-inflammatory responses in gastric epithelial cells via the delivery into cells of (i) peptidoglycan (PGN) or (ii) the effector protein CagA. (Figure published in Fox and Wang J Clin Invest 2007 117: 60-9.)

Fig. 3 H. pylori bacteria (purple colour) adhering to gastric epithelial cells. The highly refringent particles correspond to radioactively-labelled peptidoglycan, released by the bacteria. Highly refringent zones represent foci of peptidoglycan accumulation. (R. L. Ferrero; A. Cardona and C. Soubert, Institut Pasteur, Paris.)

Current Funding:

NHMRC project grant 334127 (2005-2007)
“The role of the intracellular pathogen-recognition molecule Nod1 in the host response to Helicobacter pylori infection.”

NHMRC project grant 384232 (2006-2008)
“Identification of novel colonisation factors in Helicobacter pylori.”

CASS Foundation Ltd. (2007)
“Understanding the molecular processes involved in Helicobacter pylori induced inflammation; a precursor of peptic ulceration and stomach cancer.”

Publications (since 2004)

1. Fritz, J. H., Le Bourhis, L., Sellge, G., Fsihi, H., Kufer, T. A., Collins, C., Viala, J., Magalhaes, G. J., Ferrero, R. L., Girardin, S. E., Philpott, D. J. (2007) Nod1-mediated peptidoglycan recognition controls the onset of adaptive immunity. Immunity (in press).
2. Fritz, J. H., Ferrero, R. L., Philpott, D. J., Girardin, S. E. (2006) Nod-like proteins in immunity, inflammation and disease. Nature Immunol 7, 1250-1257.
3. Ferrero, R. L., Philpott, D. J. (2005) Nod1 signaling to extracellular mucosal bacteria in epithelial cells. International Congress Series 1285, 68-77.
4. Ferrero, R. L. (2005) Innate immune recognition of the extracellular mucosal pathogen, Helicobacter pylori. Molec. Immunol 42, 879-85.
5. Viala, J. Chaput, C., Boneca, I. G., Cardona, A., Girardin, S. E., Moran, A. P., Athman, R., Mémet, S., Huerre, M. R., Coyle, A. J., DiStefano, P. S., Sansonetti, P. J., Labigne, A., Bertin, J., Philpott, D. J., Ferrero, R. L. (2004) Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nature Immunol. 5, 1166-1174.
6. Gobert, A. P., Bambou, JC., Werts, C., Balloy, V., Chignard, M., Moran, A. P., Ferrero, R. L. (2004). Helicobacter pylori Heat Shock Protein 60 mediates interleukin-6 production by macrophages via a Toll-like Receptor (TLR)-2-, TLR-4- and Myeloid Differentiation factor 88-independent mechanism. J. Biol. Chem. 279, 245-250.