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Richard Farndale

Collagen receptors and collagen-binding proteins

Collagen, the most abundant protein in the body, has an obvious structural role, as in bone, tendon and skin, serving as a scaffold upon which the extracellular matrix assembles.  Several cell-surface collagen receptors also allow collagen to regulate cell behaviour.

Over the past few years we have produced the Collagen Toolkits, overlapping synthetic triple-helical peptides (THPs) that span the entire triple-helical (Col) domains of collagens II and III.  These peptide libraries allow us to map within collagen the interaction sites of collagen binding receptors and matrix components.  We work primarily on the collagen-binding integrins, a1b1, a2b1, a10b1 and a11b1, and on immune receptors related to Glycoprotein (Gp) VI, LAIR1 and OSCAR, as well as on the discoidin domain receptors, DDR1 and DDR2.  Our interests are broadening further to include, for example, matrix metalloproteinases, fibronectin and a diverse set of bacterial adhesins.

We collaborate widely in this activity, and have set up a website to facilitate access to our materials and expertise:

We design specific THP ligands for the above, and are working to use these as components of biomaterials.  The group has a long-standing interest in thrombus deposition on collagens of the blood vessel wall, mediated directly by platelet Gp VI and integrin α2β1, and indirectly by von Willebrand factor/Gp Ib.

Funding for the group is through Programme, Project and New Horizons Grant support from British Heart Foundation, a Biomedical Resource Grant from Wellcome Trust and equipment grants from Sir Isaac Newton Trust.

Lab members: Dominique Bihan, Alex Bussey, Samir Hamaia, Joanne-Marie Howes, Stephanie Jung, Peter Kim, Jean-Daniel Malcor, Masaaki Moroi, Rachael Stone, Ben Watson, Long Zhou

Collagen toolkit website

 

Key publications:

1. Farndale RW et al (2008) Cell-collagen interactions: the use of peptide Toolkits to investigate collagen-receptor interactions Biochem Soc Trans 36, 241-250.

2. Pugh, N et al (2010) Synergism between platelet collagen receptors defined using receptor-specific collagen-mimetic peptide substrata in flowing blood. Blood 115, 5069-5079.

3. Boilard E et al. (2010) Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 327, 580-583

4. Barrow AD et al (2011) OSCAR is a collagen receptor that co-stimulates osteoclastogenesis in DAP12-deficient humans and mice.  J Clin Invest 121, 3505-3516.

5. Munnix IC et al (2008) Collagen-mimetic peptides mediate flow-dependent thrombus formation by high- or low-affinity binding of integrin alpha2beta1 and glycoprotein VI.J Thromb Haemost 6, 2132-2142.