Arthritis & inflammatory diseases
Medical Research Scotland is one of the largest and most comprehensive independent research charities in Scotland. Unlike most medical research charities, our funding isn't restricted to any one disease or condition, we support high-quality research that aims to improve the understanding, diagnosis, treatment and prevention of all diseases and disease mechanisms.
Awards in the past 20 years
The following are some of the awards we made for research into arthritis and a range of other inflammatory or immune disorders.
Dr Alasdair MacKenzie (School of Medical Sciences, Aberdeen University) to supervise Ms Elizabeth Hay during her PhD Studentship, "The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy." This research will also involve close working with GW Pharmaceuticals.
The cannabinoid-1 receptor protein (CB1) has been implicated in obesity, addiction and chronic inflammatory disease and represents an excellent drug target for their treatment. However, promising drugs designed against CB1 can cause unacceptable side-effects in a proportion of patients. Little evidence exists that mutations in the gene that makes CB1 are involved in disease progression or drug side effects. Could mis-regulation of the CB1 gene be to blame? We have shown that obesity and addiction associated mutations alter genetic control switches required to regulate the healthy expression of the CB1 gene. We also show that activating the CB1 protein activates these switches, demonstrating self-regulation, but that disease-associated mutations disable these control switches. These mutations also change susceptibility of the switches to epigenetic modification; a process influenced by early life events. We will further investigate the switches that regulate the CB1 gene in brain regions that control inflammation and appetite where we believe genetics and the environment interact to influence disease susceptibility and drug-side effects. This project will also test novel drug treatments in development by GW Pharmaceuticals to manipulate these switches aiming to accelerate the development of personalised cures for inflammatory diseases, addiction and obesity.
Professor Iain McInnes (Centre of Immunobiology, Glasgow University) to supervise Brian Morton during his PhD Studentship, "The role of microRNA-155 as a master-switch determining the balance of inflammation and fibrosis in chronic disorders". This research will also involve close working with Lamellar Biomedical Ltd.
New molecules called microRNA (miR) have been discovered recently. They are safeguards of normal cell behaviour thus organ function. Their malfunction often leads to development of diseases: we discovered that too much of one of these molecules (miR-155) is associated with severe inflammation (e.g. arthritis). However, too little is associated with fibrosis (e.g. lung fibrosis). This project aims to find out how miR-155 works; and how it can be controlled as a new treatment strategy for arthritis and pulmonary fibrosis. The key cellular functions controlled by miR-155 will be studied in mouse models of arthritis or lung fibrosis as well as in cells taken from patients with arthritis and pulmonary fibrosis. In order to restore tissues' normal functions, we will bring back the proper levels of miR-155 in experimental arthritis and fibrosis using a new safe method of drug delivery developed by a Scottish biomedical company. We hope to discover the cell functions controlled by miR-155 and how they are associated with disease processes, and the feasibility of reversing tissue pathology by modifying miR-155. There is no effective therapy for lung fibrosis and treatment-resistant arthritis. Therefore our project may provide a novel way of controlling these diseases.
Professor Colin Campbell (School of Chemistry, Edinburgh University) to supervise Miss Hannah Johnston during her PhD Studentship, "Systems redox biology analysis of a novel family of naturally-derived anti-oxidants/anti-inflammatories". This research will also involve close working with Aquapharm BioDiscovery Ltd.
The regulation of cellular redox potential is important in controlling the behaviour of healthy cells and its dysregulation is implicated in the initiation and proliferation of several disease states. Redox potential is a measure of the driving force for oxidation and oxidative changes are known to be important in the initiation or proliferation of a variety of diseases including arthritis, chronic obstructive pulmonary disease (COPD), Alzheimer's disease, age-related macular degeneration and multiple sclerosis. Aquapharm Biodiscovery Ltd. has recently discovered a new family of molecules which have therapeutic potential as anti-oxidants or anti-inflammatory drugs in diseases such as those listed above. It is thought that this family of molecules works by interacting with pathways involved in cellular redox regulation. Our aim in this project is to use a combination of cutting-edge biophysical techniques, established molecular biology assays and a new approach to visualisation and interpretation of this data to understand the mode of action of Aquapharm's therapeutic molecules with a view to optimising their effect. Through combining quantitative measurements with a systems biology approach we will produce a quantitative map of redox potential distribution in the cell that offers a completely new way to analyse the effects of molecules which alter redox-regulation.
Dr David Meek (Medical Research Institute, Dundee University) to supervise Mr Sumanth Iyer during his PhD Studentship, "Improving the sensitivity of a novel PIM kinase-targeted therapeutic agent, CXR1002, through identification and modulation of cross-talking pathways". This research will also involve close working with CXR Biosciences
PIM protein kinases are a group of highly related signalling molecules that normally regulate the growth and survival of cells. Failure of cells to regulate these molecules occurs in a range of diseases including cancer. The development of drugs that inhibit these molecules offers the potential to block the contribution PIM kinases make to the development of disease. Defining pathways that interact or cooperate with PIM will improve understanding of basic disease processes. Defining approaches to improve sensitivity to the recently-developed PIM inhibitor (CXR1002) should benefit continued clinical trials and, ultimately, effective patient treatment.
Professor Mark Bradley (School of Chemistry, Edinburgh University) to supervise Mr Matthew Simmonte during his PhD Studentship, "Polymer microarrays for the rapid identification of substrates for the enrichment of rare cell types, mitochondrial DNA capture and peptide deformylation and scale-up for practical application". This research will also involve close working with Altrika Ltd.
Polymers have a huge medicinal potential, ranging from the passive (e.g. blood bags and catheters) to the invasive, with stents, dissolvable stitches and polymeric-based drug release systems all having a role in modern healthcare. We have developed technology which allows the efficient, streamlined creation and screening of thousands of polymers allowing the speedy identification of polymers that can control and modulate cellular function. This project aims to enable the use of the polymer microarray platform to identify new polymers for novel functional biomedical applications. In particular, the work will focus on the cellular binding and the enrichment of rare cell types from cervical smear samples and on polymers for binding or scavenging mitochondrial DNA. Identified polymers will be rapidly scaled up, allowing translation from discovery to applied materials.
Dr Heather Wilson* (Institute of Medical Sciences, Aberdeen University) to supervise Miss Miriam Obliers during her PhD Studentship, "Novel small molecule modulators of the antioxidant response pathway: potential for therapy in cancer/inflammatory disease". This research will also involve close working with Aquapharm BioDiscovery Ltd.
This project aims to develop a tiered screening strategy to detect the activity of novel secondary metabolites from purified extracts of marine organisms which show promise for the potential future development of new anti-cancer and/or anti-inflammatory drugs. The work will first try to identify which purified compounds show strong functional activity, but with minimum cell toxicity or induction of apoptosis, then the specific mechanisms and cell signalling pathways involved which allow these compounds to exert their functional ability. Thereafter, their pharmacological effects, in both in vitro model tumour cell systems and established inflammatory cell systems. Understanding the mechanisms of action and likely clinical effectiveness of potent, non-toxic and non-electrophilic compounds derived from natural marine-based secondary metabolites will be of huge benefit in developing lead compounds with minimum 'off target' effects for these two important therapeutic areas.
[*Dr Wilson took over this award, following the death of Professor Hawksworth, to whom it was made originally.]
£141,848 over 30 months to Dr Hui-Rong Jiang (Institute of Pharmacy & Biomedical Sciences, Strathclyde University), to investigate IL-33 activity in the development of neurological autoimmune diseases.
Multiple sclerosis (MS), a chronic disease which causes irreversible damage to the central nervous system (CNS), is the leading cause of non-traumatic neurological disability among young adults and its prevalence in Scotland is one of the highest in the world. There is currently no cure and existing treatments are largely ineffective. MS is an autoimmune disease in which cell-signalling proteins called cytokines play an important part. This project aims to improve understanding of the role of cytokine IL-33 in the development of MS and other neurological diseases by clarifying its role in modulating immune responses and CNS repair.
£148,940 over three years to Dr Carl S. Goodyear (Clinical Neurosciences, Glasgow University), Professor Margaret Harnett (Immunology, Infection & Inflammation, Glasgow University) & Dr Richard Soutar (Haematology, Gartnavel General Hospital, Glasgow), for a study of the inhibition of osteoclastogenesis by immunomodulatory complexes.(The Vipiana Award)
Bone destruction is associated with many diseases, including rheumatoid arthritis, periodontal disease and osteoporosis and it is thought to be result from an imbalance in the normal bone remodelling processes, with increases in the activity and number of bone-eating cells (osteoclasts), over their bone-making (osteoblasts) counterparts. This study will investigate a new therapeutic intervention that will stop the increase in osteoclast numbers and activity, while clarifying the detail of their regulation in such diseases.
£79,993 over two years to Dr Iain Anthony (Neuropathology), Professor Jeanne Bell (Neuropathology) & Dr Juan Carlos Arango (Forensic Medicine, Edinburgh University) for an investigation of neuroinflammation and accelerated neuro-ageing in HAART-treated HIV-infected individuals.
HIV-infected individuals now live much longer than previously and impairment of brain function is becoming a major problem in these people, so this study aims to clarify whether HIV or its associated treatment accelerates the natural ageing processes in the brain.
£74,044 over two years to Dr Rebecca Devon (Molecular Medicine Centre, Western General Hospital, Edinburgh) to study the role of alsin and its interacting proteins in juvenile onset amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis, a degenerative disease of the brain which results in progressive muscular weakness and ultimately fatal paralysis, is also known as motor neurone disease. This project aims to clarify the precise function of the gene known to be associated with the form of disease which starts in childhood.
£79,786 over 17 months to Drs Megan Smith (Dermatology) & Adriano Rossi(Respiratory Medicine Unit, Edinburgh University) for a study of the role of nitric oxide as a regulator of apoptosis and inflammation in human skin following ultraviolet irradiation.
Lupus erythematosus (LE) is a photosensitive condition, where even small amounts of ultraviolet radiation (the active component of sunlight) causes the death of skin cells. Ultraviolet light has, however, been shown to have beneficial effects. This study aims to clarify how it can be used safely to treat photosensitive skin conditions, such as systemic lupus erythematosus.
The Nasmyth Travelling Medical Research Scholarship 2004-06 was awarded to Dr Anna Claire Williams (Neurology, Lothian University Health NHS Trust) to travel to the laboratories of INSERM and the CNRS in Paris to investigate oligodendrocyte guidance molecules in multiple sclerosis lesions and in experimental models of demyelination and remyelination.
The Cruden Medical Research Scholarship 2003-04 was awarded to Dr Claire A. Higgins (Obstetrics & Gynaecology, Aberdeen Maternity Hospital) to carry out a serial analysis of protein expression in anogenital lichen sclerosus.
£80,000 over two years to Dr Julia V. Marley & Professor A. Neil Turner (Renal & Autoimmunity Group, Centre for Inflammation Research, Edinburgh University) for a study of the manipulation of tolerance to the Goodpasture autoantigen.
Immune tolerance is the natural process by which the body protects itself from self-attack by its own immune system. However, this fails in kidney inflammation, for example that occurring in Goodpasture's Disease. This research aims to alter the immune response to improve tolerance when it fails.
£42,965 over one year to Drs Trevor R. Walker & Ian Dransfield and Professor Christopher Haslett (Centre for Inflammation Research, Edinburgh University) to study inflammatory cells and lung injury, using imagine activation of neutrophil function by integrin-mediated adhesion.
Leukocytes (white blood cells) are part of the body's natural cellular defence mechanisms. However, sometimes they can over-react causing cell damage, particularly if they are in prolonged contact with blood vessel walls. By studying the cellular effects which result when this prolongation occurs, this research seeks to establish the trigger from defence to damage.
£64,813 over two years to Dr Stephen J. Yarwood (Division of Biochemistry & Molecular Biology, Glasgow University) to investigate the role of EPAC proteins in inflammatory responses.
The protein EPAC is activated by cAMP, which has anti-inflammatory properties. As inflammation is the basis of numerous disorders, manipulating EPAC could prove a possible mechanism for new anti-inflammatory treatments.
£69,996 over two years to Drs Yatishkumar Lad & Tariq Sethi (Respiratory Medicine Unit, Edinburgh University) to investigate the mechanism underlying Raf-mediated integrin suppression.
Cell adhesion is regulated by receptors called integrins, which can control adhesion from within the cell, by a process known as 'inside out signalling'. Initial work suggests 'inside out signalling' to integrins occurs via a new, undescribed pathway, which this research hopes to gain an insight into.
£69,924 over two years to Dr Renate Kain (Pathology, Aberdeen University) for the identification of gp130 - a novel target of autoimmune attack in glomerulonephritis.
In focal necrotising glomerulonephritis the healthy cells of the kidney are attacked by antibodies made by the body's immune system. These antibodies have been shown to recognise a molecule called gp130, found in the kidney small blood vessels. The aim therefore of the research is to study gp130 and formulate a test for it.
£69,726 over two years to Dr Lars P. Erwig (Medicine & Therapeutics, Aberdeen University) for an investigation of macrophage programming in inflammation.
£13,807 to Dr Meilien Ho, Professor Jill F. Belch & Dr Margaret McLaren (Medicine, Dundee University) and Professor George Nuki (Medicine, Western General Hosptial, Edinburgh) for a pilot study lasting three months to investigate oxidised low density lipoprotein and homocysteinaemia sclerosis.
£69,369 over two years to Dr Ian Dransfield (Rayne Laboratories, Edinburgh University) and Professor Christopher Haslett (Respiratory Medicine Unit, Edinburgh Royal Infirmary) to investigate the regulation of neutrophil function by soluble E selectin in inflammatory cells and lung injury.
£49,474 to Dr Peter T. Reid, Professor Christopher Haslett & Dr Jean-Michel Sallenave (Respiratory Medicine Unit, Rayne Laboratories, Edinburgh University) for a one-year study of inflammatory lung disease and the regulation of secretion of the low molecular weight antiproteinase elafin.
£69,954 to Professor Foo Y. Liew (Immunology, Glasgow University) for a two-year project involving the cloning of molecules on T cells inducible by IL-15 but not by IL-2 in rheumatoid arthritis using differential display and suprression subtractive hybridisation.
£39,824 to Dr Seamas Donnelly (Rayne Laboratory, Edinburgh University) & Professor Christopher Haslett (Respiratory Medicine, Edinburgh Royal Infirmary) for a one-year study of macrophage migration inhibotory factor (MIF) and inflammatory lung disease.
£31,967 to Dr Margaret M. Harnett (Immunology, Glasgow University) and Professor Roger D. Sturrock (Centre for Rheumatic Diseases, Glasgow Royal Infirmary) to investigate whether lesions in phospholipase A2 signalling in FAS and TNF-mediated T-cell apoptosis break periperal tolerance, inducing autoimmune disease such as rheumatoid arthritis.
£68,332 to ProfessorWilliam J. Harris (Molecular & Cell Biology, Aberdeen University) for a study involving the identification of the repertoire of autoantigens recognised by B and T cells from patients with multiple sclerosis.
£56,805 over two years to Professor Alex Elliott & Mr Keith McKellar (Clinical Physics, Glasgow University), Professor James McKillop (Medicine), Dr Brian Neilly (Nuclear Medicine) and Dr Curtis Gemmell (Biochemistry, Glasgow Royal Infirmary) for a study involving novel radiopharmaceutical approaches to inflammation imaging.
£15,320 for one year to Drs Jill J.F. Belch & F. Khan (Medicine, Dundee University) and Dr Margaret McLaren & Sister Roberta Littleford (Vascular Medicine, Ninewells Hospital & Medical School, Dundee) for a study of fibrinolysis and endothalial cell function in patients with Raynaud's Phenomenon.
£73,000 over two years to Dr David I. Stott (Bacteriology & Immunology, Glasgow University) for a study of the genetic origins and control of expression of autoaggressive B-cell clones in systemic lupus erythematosus.
£54,014 over two years to Dr Donald M. Salter (Pathology, Edinburgh University) to investigate the potential of tenascin as a serological marker of arthritis and to assess its role in articular cartilage degeneration and repair.