Immune Modulation
Professor DI Pritchard
The Immune Modulation Research Group adopts a pioneering approach to address many important and outstanding questions in immunology, with a view to understanding a number of key host-pathogen interactions and to developing new therapeutic drugs and vaccines.
Current projects include:
The molecular basis underpinning wound healing by the medicinal maggot Lucilia sericata
The therapeutic benefits of live hookworm infection on allergic and autoimmune diseases
Bacterial quorum sensing signal molecules as chemical templates for new generation immune suppressive drugs and vaccines
Exploring plants to discover new therapeutics
The molecular basis for allergenicity
The molecular basis underpinning wound healing by the medicinal maggot Lucilia sericata .
Termed 'Biotherapy without the Beasties', we are investigating the bioactive molecules secreted by this insect, and their effects on cell behaviour in the wound, effects considered conducive to healing (click on the image below to watch a movie on the healing power of maggots).
At the same time, we are in the process of developing prototype bioactive dressings with Molnlycke Health Care in Sweden and the University of Bradford . The project also addresses fundamental questions about the interaction between the immune systems of vector insects and mammals, knowledge applicable to disease transmission (malaria, sleeping sickness, river blindness) and the pathology of insect bites (Waltham Centre for Pet Nutrition )
The therapeutic benefits of live hookworm infection on allergic and autoimmune diseases.
The aforementioned diseases result from an overactive immune system, and are currently treated with relatively toxic immune suppressive drugs or expensive monoclonal antibody formulations. Our forward view is that we should harness the intrinsic immune suppressive capacity of human parasites such as the hookworm Necator americanus (click on the image below to watch a movie of Necator americanus in the small intestine).
Our work in Papua New Guinea since 1988 has illustrated the complexity of the immunological relationship between hookworms and the immune system, and we continue to explore this relationship in the field, and in a clinical trials context in Nottingham (asthma, view a poster on our asthma studies Crohn’s disease and MS).
Bacterial quorum sensing signal molecules as chemical templates for new generation immune suppressive drugs and vaccines.
Our laboratory was the first to demonstrate the immune suppressive capacity of these molecules, which bacteria use to gain a foothold in the body, and we are using this knowledge to develop new therapeutics for autoimmune diseases, and to develop vaccines against Pseudomonads and other organisms of importance which utilise quorum sensing as a means of communication (http://www.nottingham.ac.uk/quorum/ ).
Exploring plants to discover new therapeutics
The group has a keen interest in assaying phytochemical extracts from the Kew Gardens collection, and from our campus in Malaysia and Mars UK . These extracts are screened through a panel of sophisticated immunological assays prior to the selection of active extracts for refinement.
The molecular basis for allergenicity
The IMRG has long been interested in what makes a protein an allergen, still a fundamental question in immunology, and has conducted pioneering work on the innate allergenicity of proteinase antigens , as found in dust mites and parasites. This work has been expanded to encompass chitins, and explores the role of chitinases in host-defence and immune pathology. The group also investigates the role of the basophil in triggering innate immune responses, and in pathology and immunity to parasites.
Staff:
Head of group: Professor David Pritchard , BSc (University of Wales, Bangor), PhD (University of Birmingham)
Senior Research Officer: Dr Alan Brown , BSc (University of Surrey), PhD (Nottingham Trent University)
Research Students:
Catherine Pereira (EPSRC /Astra Zeneca Doctoral Training Centre for Targeted Therapeutics )
Nicholas Allen (BBSRC)
Selected Publications:
1. Gaisford W, et al
OdDHL inhibits T cell subset differentiation and delays Diabetes onset in NOD mice
Clinical and Vaccine Immunol. 2011:18(8):1213-20
2. Ting KN, Othman M, Telford G, Clarke G, Bradshaw TD, Khoo TJ, Loh HS, Wiart C, Pritchard D, Fry JR
Antioxidant, cytoprotective, growth inhibitory and immunomodulatory activities of extracts of Dysoxylum cauliflorum Hiern., a Malaysian Meliaceae
J Medicinal Plants Research, 2011:5:5867-5872
3. Pritchard D
Worm Therapy: For or Against?
J Helminth. 2011:85(3):225-227
4. Britland ST, Smith AG, Finter WF, Vowden K, Vowden P, Telford G, Brown A, Pritchard D, Eagland D
Recombinant Lucilia Sericata Chymotrypsin in a Topical Hydrogel Formulation Degrades Human Wound Eschar Ex Vivo
Biotechnology Progress. 2011:27(3):870-874
5. Jadhav GP, Chhabra SR, Telford G, Hooi DS, Righetti K, Williams P, Kellam B, Pritchard DI, Fischer PM.
Immunosuppressive but Non-LasR-Inducing Analogues of the Pseudomonas aeruginosa Quorum-Sensing Molecule N-(3-Oxododecanoyl)-l-homoserine lactone
J Med Chem. 2011:54(9):3348-59. PubMed PMID: 21488685