Research Groups
Introduction
Blundell Brindle Broadhurst Brown Carrington Dupree Evan  Head of Dept. Farndale Gay Grace Griffin Hendrich Hesketh Higgins Hollfelder Hong Howe Hyvonen Jackson S Jackson T Jackson R Laue Leadlay Lester Lilley Lipkow	Livesey Luisi Lummis Mata McCafferty Metcalfe Mishima Miska Monie Mott Murzina Nietlispach Owen Oliver Packman Pellegrini Robinson Salmond Scadden Silva Smith A Smith C Standart Thomas Timmers Tolkovsky Welch Zhang
Past members

Collagen receptors: Integrins and Glycoprotein VI

Research Groupings: Cardiovascular science and medicine | Developmental and regenerative biology and medicine

The collagen receptors mediate the attachment of a wide variety of cells to connective tissues in diverse pathophysiological contexts. The major interest of the group is the interaction between blood vessel wall collagens and the platelet surface, a process which is fundamental to haemostasis and thrombosis. Adhesion requires integrin α2β1, whereas platelet activation involves mainly Glycoprotein VI, a receptor of the immunoglobulin family.

Platelets deposited from whole blood at arterial flow rate on collagen-coated surfaces.

Left is control, showing aggregates of platelets. Right is blood treated with anti-GpVI single chain antibody, showing prevention of aggregation, whilst primary adhesion is not impaired, (Siljander et al, 2004).

We synthesise triple-helical fragments of collagens which are selective for different collagen receptors, which allows us to study α2β1 and GpVI in isolation, and have recently located the binding site in collagen III for von Willebrand factor (VWF), completing the important adhesive motifs in collagen that recognise the platelet surface. Thus we are tackling the adhesive and signalling properties of GpIb along with the collagen receptors, processes measured under physiological shear conditions using the confocal microscopes recently installed in the lab.

We are applying our collagen peptide libraries to a series of collagen-binding proteins, both from the matrix and the cell-surface, and we are making a set of collagen-mimetics for diagnostic purposes.

We collaborate closely with Dr Willem Ouwehand (Dept Haematology), with whom we have identified blocking single chain antibodies for GpVI which are being developed as anti-thrombotics.

The group is largely funded by Medical Research Council and British Heart Foundation, with additional support for peptide synthesis from Wellcome Trust. We participate in an EU Framework 6 project aimed at establishing the genetic control of collagen signalling in platelets and its relationship with thrombotic disease and bleeding disorders.

Lab members
Dominique Bihan, Nicola Foad, Samir Hamaia, Joanne-Marie Howes, Gavin Jarvis, Ben Maddox, Nick Pugh, Anna Simpson, David Slatter, Christiane Smerling

References