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Infection, Inflammation and Research

These inter-related fields of research are particularly strong at Barts and The London with world-class researchers in all the major Institutes of the School.

In the 2008 Research Assessment Exercise, the Blizard Institute of Cell and Molecular Science, returned in Hospital Subjects, was ranked joint 1st in the UK with Cambridge and Edinburgh in terms of 3* and 4* outputs and was joint 7th overall out of 28, ahead of Manchester, Newcastle and Southampton.

The William Harvey Research Institute, returned in Preclinical and Human Biological Sciences, was ranked 3rd in terms of 3* and 4* outputs, and 4th overall out of 13, ahead of Kings College London, Bristol and Nottingham.

Mycobacterium Reference Unit

The School plays an integral role in the UK’s fight against TB through the Health Protection Agency’s Mycobacterium Reference Unit, led by Professor Francis Drobniewski.

The Unit’s work involves collaborations with academic staff in the School’s Centres for Infectious Diseases and Primary Care, as well as community health staff throughout east London. Barts and The London School of Medicine and Dentistry, and the Trust are recognised as being at the forefront of research and clinical practice in TB.

The MRU detects, identifies and isolates mycobacteria - the organisms which cause TB - and advises on treatment. Its research interests include all aspects of TB and related diseases - particularly the interaction of TB and HIV (a growing health concern) - both in the UK and internationally. It is one of a global network of 23 such units run by the World Health Organisation (WHO).

Focus is on disease diagnosis, the molecular epidemiology of TB and HIV, understanding drug resistance and disease tropisms, and broader translational research and public health problems posed by these diseases both in the UK and overseas. An international group of staff work on collaborative national and international clinical, laboratory and public health topics relating to TB and HIV in Russia and Ukraine and in partnership with institutions in Africa.

Mycobacterium Reference Unit [Health Protection Agency]

HIV Research

HIV Research led by Professor Aine McKnight focuses mainly on the interface between HIV and the immune system with regard to humoral immunity and a novel innate immune mechanism (Lv-2) that inhibits HIV replication after cellular entry resulting in abortive infection. She has mapped the two viral genes involved in overcoming this antiviral effect and is currently mapping the host gene(s) involved.

Other current research interests lie in HIV tropism and coreceptor use. HIV infects mainly T-cells and macrophages through the use of CD4 and co-receptors usually either CCR5 or CXCR4 chemokine receptors. Recently, we have shown that viral envelopes amplifed directly from plasma almost always additionally use a related chemokine receptor CCR3 just as efficiently as CCR5.

Professor Aine McKnight is also among a number of scientists taking part in a $25.3 million international research consortium searching for an HIV vaccine. The grant is one of the largest awards in a $287 million, five-year programme of 16 grants provided by the Bill and Melinda Gates Foundation to establish an international network of HIV vaccine discovery consortia, known as the Collaboration for AIDS Vaccine Discovery.

There is also extremely strong translational HIV research funded by the MRC and led by Dr Claudia Estcourt.

Immunology and inflammation in the gastrointestinal tract

Immunology and inflammation in the gastrointestinal tract is the subject of Professor Tom MacDonald's research group. His principal research effort is to try to understand the reasons why individuals develop Crohn’s disease, a serious inflammatory disease of the gut. Professor MacDonald identified the key role of the cytokine TNFα in Crohn’s disease, which has led to successful new therapies.

Principally funded by the MRC, BBSRC and EU FP7 and with a very strong European collaboration, MacDonald has published extensively in top journals on the control of TGFβ signalling in the gut. Ongoing studies are aimed at trying to tolerise gut T cells in Crohn’s disease to reset the immunologic thermostat, which controls immunity in the gut of healthy people.

Professor MacDonald works alongside other immunologists such as Dr Dan Pennington (funded by the Wellcome Trust) and Dr Andy Stagg, the world leader in the study of dendritic cells in the gut.

Inflammation research investigates the basic mechanisms controlling various components in inflammation and the potential to modify these using, for example, gene-therapy, anti-inflammatory peptides, and agonists and antagonists that target novel inflammatory pathways. These highly integrated programmes of research use a range of techniques from molecular biology and genetic engineering of cells and molecules, to in vivo models of inflammation, where we have a great strength.

Centre of Experimental Medicine and Rheumatology

A strategic investment of £1.45 million has been made to create a new Centre of Experimental Medicine and Rheumatology with a strong research programme in joint and tissue repair and stem cell therapy, headed by Professor Costantino Pitzalis. The strong translational element of this grouping funded by Wellcome, ARC and MRC is tightly linked into the Barts and The London NHS Trust clinical rheumatology service.

Biochemical Pharmacology group

The Biochemical Pharmacology group under Professor Rod Flower FRS and Professor Mauro Perretti, investigates the mechanism of action of anti-inflammatory drugs including Cox inhibitors (Nature Reviews Drug Discovery 2004) and especially the glucocorticoid steroids (PNAS 2002; Journal of Immunology 2003; Blood 2005). Much of the research investigates the pharmacology and the biology of Annexin A1, a protein that is induced by glucocorticoids and has profound immunomodulating properties. Funded by the Wellcome Trust (programme and projects; >£1.6 million) and the British Heart Foundation (£225,000 project), this line of research spans all aspects of Annexin A1 biology ranging from cell biology through to its role in human disease (Nature Medicine 2002; The FASEB Journal 2006, 2008; Blood 2006, 2007 and 2008; JBC 2007; Nature Reviews Immunology in press).

Other major research areas evolve around galectins (fellowships of the Arthritis Research Campaign [ARC] UK; £600,000) and melanocortin peptides (£230,000, arc UK). Industrial funding derives from Unigene Corp (NJ; $1.2 million, with licencing of 2 patents), Action Pharma (£250,000 melanocortin research) and UCB (£180,000), with other drug discovery work funded by Heptagon Fund.

Centre for Microvascular Research

A recent recruit is Professor Sussan Nourshargh who relocated to Barts and The London in 2007 from Imperial College to establish and head the Centre for Microvascular Research within William Harvey Research Institute. Professor Nourshargh’s work employs a multi-disciplinary approach to investigate events within the microvasculature and her innovative imaging applications to the study of leukocyte-vessel wall interactions are internationally acknowledged. Specific research avenues include investigations into mechanisms associated with leukocyte trafficking, vascular permeability, vascular flow and generation and regulation of vascular integrity, morphology and function, using both in vitro and in vivo models. The Centre is funded by a Programme grant from the Wellcome Trust and several other grants from the British Heart Foundation, the Arthritis Research Campaign, Wellcome Trust, AstraZeneca, Barts and The London Charity and EUC.

Bone and Joint Research Unit

The Bone and Joint Unit is a leading centre for inflammation research, which, under Professor Yuti Chernajovsky, works on the development of gene transfer strategies for the treatment of rheumatoid arthritis and other autoimmune diseases via cellular engineering, molecular design and genetic engineering.
The group has extensive funding from the AR UK, NMSS, BHF and MRC. One recent development has been the design of latent cytokines by recombinant DNA technology. The designed fusion protein between the latency associated peptide (LAP) of TGFβ and a cytokine with therapeutic potential are linked via a metalloproteinase (MMP) cleavage site which renders the cytokine inactive until it reaches a site of inflammation

The LAP provides a shell that inhibits the interaction of the cytokine with its receptors increasing its half life and ensures delivery to sites of disease.

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