Caveolae and membrane trafficking in vascular permeability
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Caveolae are small flask-shaped invaginations of the plasma membrane. They are only found in vertebrates, and are very abundant at the surface of endothelial cells and adipocytes. Major goals of our research include to determine the molecular mechanisms that generate caveolae, and to better understand their physiological roles.
There is a substantial literature linking caveolae to the regulation of endothelial permeability, the regulated transport of macromolecules across endothelial cells being central to the correct functioning of our closed, pressurised vascular system. Despite the physiological and medical importance of this process, most underlying molecular and cell biological details remain obscure.
This PhD project aims to determine the role of caveolae in trans-endothelial transport of macromolecules. Extensive use of mouse and tissue culture models will allow development of imaging and more quantitative assays for this transport, and we have already developed appropriate knockout mice lacking key caveolar genes. The primary vascular system that will be studied, at least initially, is that of the brain. This is attractive experimentally, as endothelial cells of the blood brain barrier are highly impermeable to passive / diffusive passage of macromolecules, and provides a highly medically relevant system. The project will provide training in conventional molecular biology and biochemical approaches, as well as more specialised techniques including gene editing using CRISPR, 2-photon imaging, and in vivo assays using mice.