Novel anti-chemokine peptides from ticks
Chemokines function to recruit inflammatory cells and are well-validated therapeutic targets in atherosclerosis, rheumatoid arthritis, inflammatory bowel disease and atopic dermatitis. The 46 chemokines and 20 receptors form a complex and robust network, driven by the binding of individual chemokines to several receptors and individual receptors to several chemokines, and by the expression of multiple chemokine receptors on individual inflammatory cell types. Network robustness likely underlies the failure of anti-chemokine pharmacological approaches that target individual network nodes. Ticks have evolved small salivary peptides (evasins) that suppress chemokine-driven inflammation by binding and neutralizing multiple chemokines simultaneously. Three evasins have been cloned, and have been shown to suppress inflammation in several pre-clinical models including atherosclerosis, heart, pancreas, joints, and lungs. Our working model is that the evolutionarily honed ability to target many chemokines simultaneously is the basis for evasin efficacy in inflammation, and is an important biological property not possessed by alternative anti-chemokine technology. Using a novel yeast display technology, we have cloned and expressed 30 novel evasins from diverse tick species, and our on-going work shows that they bind and neutralise chemokine function. We hypothesise that these novel evasins possess distinct chemokine neutralising activities that could be used to combinatorially target chemokines in immuno-inflammatory diseases.
Date: 21 January 2016, 12:00 (Thursday, 1st week, Hilary 2016)
Venue: Kennedy Institute of Rheumatology, Headington OX3 7FY
Venue Details: Bernard Sunley Lecture Theatre
Speaker: Prof Shoumo Bhattacharya (University of Oxford)
Organising department: Kennedy Institute of Rheumatology
Organisers: Gintare Kolesnikovaite (Kennedy Institute of Rheumatology), Jo Silva (NDORMS), Wulf Forrester-Barker (University of Oxford, Nuffield Dept of Orthopaedics Rheumatology and Musculoskeletal Sciences)
Organiser contact email address:
Host: Prof Claudia Monaco (University of Oxford)
Part of: Kennedy Institute Seminars
Booking required?: Not required
Audience: Members of the University only
Editor: Gintare Kolesnikovaite