Dave is a Professor within the Wellcome Centre for Cell Matrix Reserch in the Faculty of Biology, Medicine and Health. His undergraduate and postgraduate degrees, both in Biochemistry, were from the University of Lancaster. Since moving to Manchester in 1987, Dave has had a number of positions; first as a research associate (CF Trust and Wellcome Trust funded), then as a Senior Experimental Officer within the Wellcome Trust Centre for Cell Matrix Research before finally joining the academic staff in 2003. Within the former Faculty of Life Sciences Dave has been the deputy director of the Wellcome Trust 4 year PhD programme, the head of postgraduate research progression, the deputy associate dean for postgraduate research (recruitment), and most recently he was Tissue Systems Section Head.

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.
 

Research in my laboratory is focused on understanding how the sticky, gel-like substance mucus protects the body. Research is focused on two major topics; • How does mucus protect our lungs? • How does mucus protect against gut-living parasitic worms? In the lungs, mucus is essential in keeping the airways free from obstruction. Mucus traps inhaled bugs and particles and then hair-like cells (cilia) move the mucus out of the lungs. In diseases like asthma, cystic fibrosis and chronic bronchitis too much mucus, which is stickier than normal, is produced and it is not efficiently removed from the lungs. This results in airflow obstruction, infection, damage to lung tissue and problems with breathing. We are trying to understand how mucins, the molecules that give mucus its gel-like appearance, contribute to the abnormal properties of mucus in disease. Infections by gut-living whipworms are a major public health problem, mainly in the developing world. For these studies we are using a mouse model of human whipworm infection. We discovered that the mucus barrier and its mucin components are an essential part of a well-coordinated response to protect against of gut-living worms. We are actively investigating the details of this important protective function.

Glycobiology