Vascular Tetraspanin Group

Group leader: Dr Michael G Tomlinson

Overview

Our aim is to understand the complex “forest” of cell surface proteins that orchestrate cellular function.  We study 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 nanodomains.  Such partitioning of proteins into membrane nanodomains 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 focussed on genetically modified platelets and primary endothelial cells, with 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:

• Generation and characterisation of CRISPR/Cas9 knockout cell lines
• 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