Innate Immunity and Host Defence
Train your monocytes with treats: understanding how glycosaminolyscans can modulate monocyte biology - also offered as MBiomedSc
Supervisors: Dr. Louise Randall (Medicine RMH, Doherty Inst), A/Prof Anthony Jaworowski (Burnet Inst)
Project Site: Doherty Institute and Burnet Institute
Contact: Dr Louise Randall E: louise.randall@unimelb.edu.au
Project description: Glycobiology is an exciting and rapidly expanding field of science. Glycosaminoglycans consist of repeating chains of disaccharide (2 sugar) units and are generally attached to a protein core, thereby forming a proteoglycan. These molecules have important structural roles but new functions, including roles in cell signaling and the immune system, have now been described. Monocytes are key cells of the immune system with diverse roles, which include responding to infection and aiding in repair. Data generated in our laboratories suggest that specific glycosaminoglycans can modulate the response of monocytes to pathogen products, including the malaria-causing parasite Plasmodium falciparum. This new project aims to examine the mechanisms involved in this glycosaminoglycan-dependent education of monocytes by focusing on signaling pathways within the cells. The techniques available for this project include cell culture of primary cells and cell model systems, flow cytometry, ELISA, protein analyses and realtime RT-PCR.
Immune Cell Signalling Regulation During Inflammation - also offered as MBiomedSc
Supervisors: Dr Rodney Luwor and Dr Paul Licciardi
Location: Dept of Surgery RMH and Murdoch Children’s Research Institute
Contact: Dr Rodney Luwor; T: 8344 3027, E: rluwor@unimelb.edu.au
Project Description: Infections with Streptococcus pneumoniae (pneumococcus) are a major cause of morbidity and mortality in children <5 years of age globally with ~1.5 million deaths per year due to invasive pneumococcal diseases (IPD) such as pneumonia, meningitis and sepsis. There has been recent interest in understanding the host response to pneumococcal infection, particularly on innate immunity and inflammation. Following infection, recognition of S. pneumoniae (and their bacterial components) occurs by pattern recognition receptors such as Toll-like receptors (TLRs-2,4) on monocytes and neutrophils as well as on airway epithelial cells. Activation of TLRs lead to inflammation characterised by cytokine and chemokine secretion (e.g. TNF-α, IL-1β, IL-6, IL-8) which further recruit innate immune cells mainly under the control of NFκB. In addition, large multi-protein complexes known as inflammasomes regulate caspase-1-mediated IL-1β and IL-18 release and are critical in this response. Recent studies have shown that the NLRP3/NALP3 inflammasome is integral in the host inflammatory response to pneumococcal infection but can also contribute to the associated pathology. Therefore, novel anti-inflammatory therapies that target the inflammasome would be effective in limiting the pathological consequences of pneumococcal infections. Dietary short-chain fatty acids (SCFAs) such as butyrate are widely recognised to possess potent anti-inflammatory effects. SCFAs are also produced probiotic bacteria, and represent a possible mechanism by which they exert their reported beneficial effects on inflammation, immune modulation and pathogen colonisation. This study aims to assess the biological role of butyrate on NFkB- and inflammasome-driven responses using a bacterial infection model recently developed in the laboratory.