We investigate how mammalian cells interact with their extracellular environment in health and disease
My group has two main interests:
Understanding Notch receptor activation. We aim to understand the cell surface organisation of the Notch receptor, its interaction with ligands, and its regulation using a range of molecular, cellular and whole organism methods. The Notch pathway is a universally conserved signaling system in metazoan organisms. Not only does it play a key role in development, but the pathway also regulates cell proliferation, apoptosis and angiogenesis. Many diseases including a range of cancers arise as a result of gene mutations in Notch pathway components. By understanding the molecular mechanisms involved in receptor -ligand recognition and activation, we hope that novel therapies will be developed to modulate the Notch signal in different biological processes.
The role of fibrillin-1 microfibrils in regulating TGFβ activation, a crucial extracellular matrix cytokine.We also study the structure, assembly and interactions of the extracellular matrix fibrillins, and the mechanisms by which disease-causing mutations result in the connective tissue disorders Marfan syndrome and the acromelic dysplasias. Our recent structural studies have enabled us to create a GFP-labelled form of fibrillin-1. This has allowed us to track the fate of normal and mutant fibrillin-1 forms in the process of microfibril assembly using a co-culture system We are also currently studying fibrillin-1 intermolecular interactions with the LTBPs in order to gain insight into the role of the fibrillin microfibril matrix in regulating the process of TGFβ activation.