The role of mucins in the protection of mucosal surfaces
The overall aim of my research is to define the roles of polymeric mucins in mucosal biology. At present my main focus is to explore the roles of these glycoproteins in (i) respiratory disease, and (ii) protection against intestinal nematodes. The airways mucus gel performs a critical function in defending the respiratory tract against pathogenic and environmental challenges. However, overproduction of airways mucus with abnormal transport properties is an important pathologic feature of common respiratory disorders. In normal physiology, the polymeric mucins MUC5AC and MUC5B provide the organizing framework of the airways mucus gel and are major contributors to its transport properties. Entanglements, along with specific non-covalent interactions, of these polymers are key elements in mucus gel formation. Importantly, we have shown the relative amounts of MUC5AC and different glycosylated variants of MUC5B are altered in hypersecretory disease compared to normal airways mucus. However, at present there is no definitive link between changes in mucus transport properties and either mucin biochemistry or macromolecular structure. Currently we are investigating the role(s) of MUC5AC and MUC5B, and their equine orthologues, in human asthma and cystic fibrosis, and in equine recurrent airway obstruction.
In the other main focus of my research (in collaboration with Professor Richard Grencis, FBMH, University of Manchester), we are actively exploring the function of mucins and other goblet cell products, in intestinal nematode infection. For these studies we are using the nematode Trichuris muris (T. muris) in a mouse model of human Trichuriasis. Expulsion from the intestine of T. muris is dependent on TH2-associated cytokines. Our studies have highlighted that the mucus barrier is a significant component of the well-coordinated response initiated against the nematode, influenced by the TH2-type cytokines. Work is on going to define the functional role of the mucins in the expulsion of intestinal dwelling nematode parasites.