Vascular Tetraspanin Group

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Group leader: Dr Michael G Tomlinson

Overview

Our aim is to understand the complex “forest” of cell surface proteins that orchestrate cellular function.  We focus on platelets, the first aid kit of the bloodstream, and the endothelial cells that line our blood vessels, because of their critical roles in health and disease processes leading to heart attack and stroke.

Our research group

Platelets and endothelial cells play essential roles in maintaining blood vessel integrity and in wound healing, but can also give rise to the initiation and progression of atherosclerosis, leading to heart attack and stroke. These cells possess an array of receptors and adhesion molecules that regulate their function in health and disease. The tetraspanins are a superfamily of transmembrane proteins that interact with and “organise” other cell surface proteins into membrane microdomains. Such partitioning of proteins into membrane microdomains is critical for processes such as cell signaling and adhesion. Indeed, the fundamental importance of tetraspanins is underlined by their expression throughout the animal, plant and fungal kingdoms. By identifying novel tetraspanin-associated proteins on platelets and endothelial cells, and characterizing their regulation within tetraspanin microdomains, we aim to identify new drug targets for the prevention and treatment of cardiovascular disease.

Our studies are heavily focussed on genetically modified platelets and primary endothelial cells, with some additional use of cell line models.  The techniques that we employ include genomics and proteomics, molecular biology, functional assays for platelets and endothelial cells, and analyses of protein-protein interactions through advanced microscopy and biochemical methods.

Specialist techniques:

  • Biochemical analyses of protein-protein interactions for membrane proteins
  • Quantitative two-colour western blotting using the Odyssey Infrared Imager
  • Luciferase reporter assays as a readout for cell signalling pathways

Current Projects

  • Regulation of platelet and endothelial cell surface receptors by tetraspanin microdomains (British Heart Foundation Senior Fellowship FS/08/062/25797)
  • Tetraspanin regulation of ADAM10: impact on atherosclerosis (British Heart Foundation PhD Studentship FS/12/79/29871)
  • Platelet function in tetraspanin Tspan9- and Tspan33-deficient mice (Biotechnology and Biological Sciences Research Council PhD Studentship)
  • The role of tetraspanin microdomains in angiogenesis (Biotechnology and Biological Sciences Research Council PhD Studentship)

Recent Publications

For full publication lists see:

Staff

Principal Investigators
Michael G Tomlinson - School of Biosciences

Postdoctoral Researchers 
Jing Yang (technician)

PhD Students 
Elizabeth J Haining
Rebecca L Bailey 
Jasmeet S Reyat

Internal Collaborators
Fedor Berditchevski - School of Cancer Sciences
Roy Bicknell - School of Immunity and Infection
Alexander Brill
Victoria L Heath - School of Immunity and Infection
Neena Kalia - School of Clinical and Experimental Medicine
Andrew L Lovering - School of Biosciences
Frank Michelangeli - School of Biosciences
Steve J Publicover - School of Biosciences
G Ed Rainger - School of Clinical and Experimental Medicine
Joshua Z Rappoport - School of Biosciences
Alice M Turner - School of Clinical and Experimental Medicine
Steve P Watson - School of Clinical and Experimental Medicine
Ben E Willcox - School of Cancer Sciences, College of Medical and Dental Sciences

External Collaborators 
Carl P Blobel (New York, USA)
Nicholas D Holliday (Nottingham, UK)
Andreas Ludwig (Aachen, Germany)
Bernhard Nieswandt (Würzburg, Germany)
Peter A Smethurst (Cambridge, UK)
Schickwann Tsai (Utah, USA)
Annemiek B van Spriel (Nijmegen, The Netherlands)