Extrinsic manipulation of urothelial tissue homeostatsis via modification of the glycome

The specialisation of the urothelium as the tightest barrier epithelium in the body is underpinned by its capacity for rapid regeneration and the restitution of a functional barrier in response to damage. Combined with the finding that urothelial cells are highly amenable to cell and tissue culture, this provides an experimental system par excellence for investigating mechanisms involved in regulating and dysregulating tissue homeostasis, including the processes of differentiation and regeneration. Although poorly defined, a role for the glycome is implicated: mature superficial cells display an apical glycocalyx that supports barrier function, whilst modifications of matrix-bound proteoglycans are implicated in the sequestration and presentation of autocrine growth factors produced by regenerating urothelium, which includes heparin-binding epidermal growth factor [Varley et al. 2005; PMID 15878346]. The purpose of this project will be to investigate the role of the glycome in urothelial tissue homeostasis by applying glycome-associated research tools and reagents available from the industrial partner, IntelliHep Ltd, to the cell and tissue culture models available in the academic laboratory. These studies are expected to open up the longer term possibility of developing new lines of tissue regenerative therapies.