The project covers the areas of Immunology, Inflammation, Drug Discovery and Parasitology; the primary supervisor is a member of the Target Validation and Drug discovery Research Group.

The Hygiene Hypothesis suggests that the recent, rapid eradication of pathogens like parasitic worms has resulted in an unbalanced hyperactive immune system that has contributed to the increased incidence of allergic and autoimmune inflammatory disease in developed countries. This has generated interest in the idea that worm infection might protect humans from developing chronic inflammatory conditions. As a consequence of this, live worms are in the process of undergoing trials as therapeutics in a range of immune system-mediated diseases. However, clearly the use of pathogens as therapeutics is not ideal and so we have focused on exploiting an isolated worm-derived molecule called ES-62; a glycoprotein we discovered in the secretions of the filarial nematode Acanthocheilonema viteae and that is anti-inflammatory by virtue of covalently attached phosphorylcholine (PC) moieties. ES-62 is generally considered to be one of the best-characterized worm-derived immunomodulators and with most potential impact for translation to the clinic. Consistent with this, we have previously shown ES-62 to exhibit therapeutic potential in allergic disease (airway and skin) and rheumatoid arthritis and more recently, have reported that it protects against development of nephritis, arthritis and accelerated atherosclerosis associated with systemic lupus erythematosus, in model systems. However there are practical problems associated with high-level production of this molecule, which would prevent its development as a drug. For this reason Small Molecule Analogues (SMAs) based around the active PC moiety have been produced and our research to date indicates that these drug-like compounds successfully mimic the properties of the parent molecule. The aim of this project is to conduct further research on the ES-62 SMAs covering such topics as the breadth of inflammatory diseases that they can be applied to and also elucidation of the SMAs' mechanisms of action at the molecular level.

A range of techniques incorporating immunology, in vivo biology, molecular biology and cell biology

1. Harnett, W. (2014) Secretory products of helminth parasites as immunomodulators. Molecular and Biochemical Parasitology, 195, 130-136.
2. Pineda, M.A. et al. (2014) ES-62, a therapeutic anti-inflammatory agent evolved by the filarial nematode Acanthocheilonema viteae. Molecular and Biochemical Parasitology, 194, 1-8