Respiratory Disease

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 respiratory disease.

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.

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.

£149,790 over three years to Dr Leanne McKay (Institute of Neuroscience & Psychology, Glasgow University), to study the development and maturation of the neural control of breathing.
Respiratory control disorders like sleep apnoea and sudden infant death syndrome are very common, but their origins are not well understood. A better understanding of how the brain generates the nerve signals that produce respiratory rhythm is crucial if ways are to be found to treat or prevent these disorders. This project aims to provide valuable new information about the mechanisms underlying development and maturation of the respiratory system.

£120,229 over 24 months to Dr Paul Hoskisson (Institute of Pharmacy & Biomedical Sciences, Strathclyde University), for a study of non-toxigenic Corynebacterium diphtheriae  -  a pathogen of emerging importance in Scotland.
Diphtheria is a debilitating disease of the throat and pharynx caused by the bacterium Corynebacterium diphtheriae. Although relatively rare in the UK thanks to an effective vaccine, it remains a common childhood illness in the developing world. TRecent increases in cases where there is serious, persistent infections of the throat, bones and heart have, however, highlighted a lack of understanding of the detailed disease mechanisms. This research aims to rectify this deficit and point the way to developing new treatments or improved vaccines.

£142,239 over 24 months to Dr John A. Marwick (formerly of the National Heart & Lung Institute, London, now at the MRC Centre for Inflammation Research, University of Edinburgh) & Professor Adriano G. Rossi (MRC Centre for Inflammation Research, University of Edinburgh) to study the impact of oxidative stress and glucocorticoids on neutrophil function and macrophage clearance.
Following publication of the results of this research (see summary below) in the Journal of Leukocyte Biology, the work has attracted widespread attention, in the medical, Scottish and overseas media, including the following: News Medical; Science Daily; Galloway Gazette; STV; BioNews Texas.
Inflammation is normally a beneficial process, involving white blood cells which kill invading organisms, remove damaged tissue and start to repair affected tissues. An acute, strong episode of inflammation can,however, damage the body's organs, especially if they are already inflamed. People with severe asthma and chronic obstructive pulmonary disease (COPD) have chronically-inflamed lungs and, if they get an infection, they often also get acute episodes of inflammation (called exacerbations). These cause an excess of white blood cells (neutrophils) and can result in hospitalisation and death. Anti-inflammatory drugs like steroids are good at controlling inflammation, but they do not work well on neutrophils and are ineffective during exacerbations. This research aims to find out why this is the case, so that new drugs might be developed which could reduce inflammation during exacerbations, thereby preventing hospitalisation and possible death.

The Cruden & the Mrs Robina Menzies Smith Medical Research Scholarships 2005-06 were awarded together to Dr Kevin Dhaliwal (Centre for Inflammation Research, Edinburgh University) for his project entitled "Macrophage-based gene therapy for neutrophil-mediated lung injury".

£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.

The Cruden Medical Research Scholarship 2001-02 was awarded to Dr Gregor M. Walker (Neuroscience & Biomedical Systems, Glasgow University) for the determination of the role of superoxide dismutase in persistent pulmonary hypertension of the newborn.

£99,826 over three years to Drs Morgan G. Blaylock & Garry M. Walsh (Medicine & Therapeutics, Aberdeen University) and Dr J. Graham Douglas (Respiratory Medicine, Aberdeen Royal Infirmary) to investigate the role of glucocorticoid receptors and caspase activation in the induction of eosinophil apoptosis in glucocorticoid-sensitive and glucocorticoid-resistant asthma.
A key process in asthma is inflammation caused by eosinophils, a type of white blood cell not found in healthy lungs. The researchers will investigate how steroid treatments cause the death of such cells, in order to develop further treatments for patients who are steroid-resistant.

£68,382 over two years to Dr Mary McElroy & Professor Christopher Haslett (Rayne Laboratories, Edinburgh Unviersity) to study the mechanism of Staphyloccocus aureus injury to the alveolar-capillary barrier in bacterial infection of the lung.

£69,990 over two years to Dr Andrew M. Wilson & Professor Brian J. Lipworth (Clinical Pharmacology & Therapeutics, Dundee University) to study the clinical and histological outcomes in allergic airways disease and the efficacy of combined mediator antagonism or topical corticosteroid treatment.

£69,225 over two years to Drs Simon Brown (Centre for Inflammation Research) & Seamus Donnelly (Respiratory Medicine, Edinburgh Royal Infirmary) to study a new mechanism promoting resolution of lung inflammation: macrophage-directed deletion of neutrophils.

£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.

£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.

£69,369 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.

A Medical Research Scholarship 1999-2000 was awarded toDr Scott M. Nelson (Queen Mother's Hospital, Glasgow) to identify prognostic indicators of pulmonary hypoplasia in fetal congenital diaphragmatic hernia and obstructive uropathy.

£40,881 over one year to Drs Jim McWhir (Roslin Institute, Edinburgh) and Peter Gilmour (Applied Chemical & Physical Science, Napier University) to investigate inactivation of the ovine cystic fibrosis transmembrane conductance regulator.

£68,806 to Professor Alison M. Gurney (Physiology & Pharmacology, Strathclyde University) for a two-year study aimed at developing a fluorescent assay for drugs that modulate pulmonary artery potassium channels.

£81,239 to Professor Anne Ferguson (Medicine) & Dr David J. Porteous (MRC Human Genetics Unit, Western General Hospital, Edinburgh) for a three-year project involving the molecular and histopathological analysis of a mouse model of cystic fibrosis.