Zebrafish as a model to understand human muscle diseases
Caveolae are abundant in many cell types which must withstand membrane stress. We are using zebrafish and mouse models to understand the role of caveolae in protecting tissues from damage, with a particular focus on muscle and the zebrafish notochord.
Structure and function of a new family of caveolar coat proteins
We are studying the structure of the cavin proteins (with Brett Collins, IMB). These elongated molecules form a unique striated coat on the surface of caveolae. By combining structural biology (X-ray crystallography, cryoelectron microscopy) with functional in vivo assays in genome edited zebrafish we are elucidating structure-function relationships of the cavin proteins.
Novel pathways of endocytosis in cultured cells and in tissues
The plasma membrane that envelops each mammalian cell plays a crucial role in detecting signals for growth or in taking nutrients into the cell. At the same time, the plasma membrane protects the cell against unwanted invaders. Many human disease conditions, including cancer and muscular dystrophy, are caused by dysfunction of the plasma membrane.
Our current research analyses the organisation, dynamics, and functions of this crucial structure – with a particular focus on surface domains termed caveolae, that are linked to signal transduction, endocytosis, and lipid regulation, to understand their role in healthy cells and their aberrant function in disease.
We use a wide range of techniques, including advanced 3D electron microscopy and real-time light microscopy together with animal models of human disease to gain insights into plasma membrane dynamics and domain organisation.
Bioengineering of novel nanovesicles for drug delivery
How are nanoparticles transported across different biological barriers from the bloodstream to their target sites? This project will use tumor xenograft models and live imaging in the zebrafish to uncover the trafficking of nanoparticles in a live organism.
Lipid droplets and immune defence
We recently discovered a novel process whereby eukaryotic cells are able to kill invading pathogens using lipid droplets. This project will use cell-based infection models and live imaging in zebrafish to identify and characterise the proteins involved.
