A joint venture between the MRF and Asthma UK supports five emerging UK research leaders in Asthma research
Dr Hans Michael Haitchi, University of Southampton
Title: The impact of pre- and perinatal ADAM33 induced airway remodeling on sensitivity to environmental challenges and the early life development of asthma.
Small changes in a particular gene, called ADAM33, are associated with the development of asthma and airway ‘twitchiness’, which is another common feature of the disease. ADAM33 is thought to play a role in the lungs of young children, possibly even before birth. What isn’t understood is how and why the altered ADAM33 gene causes susceptibility to the development of asthma. It has been found that in asthma, the ADAM33 enzyme is no longer tethered to the surface of cells in the airways and becomes ‘rogue’. A higher level of this ‘rogue’ protein is associated with poorer lung function in patients with asthma. We awarded a MRF-Asthma UK fellowship to Dr Hans Michael Haitchi from the University of Southampton to investigate how airway remodelling occurs as a result of rogue ADAM33 enzyme acting on developing lung cells that it wouldn’t normally come into contact with. Dr Haitchi will also investigate whether this airway remodelling affects reactions to common irritants such as allergens early in life. The research will help to understand more about how the ADAM33 enzyme works and its interaction with environmental triggers of asthma, as well as its role in predisposing babies to develop asthma.
Dr Tara Sutherland, University of Manchester
Title: Chitinase-like proteins: the missing link in allergen-induced neutrophilic inflammation.
Inflammation is a core feature in the airways of people with asthma. People with severe, poorly controlled asthma often have a different type of inflammation than people with milder forms of the disease and the processes that lead to this difference are unclear. Many current asthma treatments don’t work well in patients with severe disease, possibly as a result of this different kind of inflammation. Dr Tara Sutherland from the University of Manchester was awarded a MRF-Asthma UK fellowship to investigate the biological function of a group of proteins that are known to be produced in higher levels in the lungs of people with asthma. These proteins have been shown to influence the recruitment of cells that cause inflammation and directly change the way in which cells function in the lung. Understanding the behaviour of different cells involved in inflammation could help to identify new targets for treatments for people with severe asthma.
Dr Aurelie Mousnier, Queens University Belfast
Title: Analysis of rhinoviruses replication complexes to identify host cell targets for the development of antiviral drugs for the treatment of asthma exacerbations.
Many people with asthma find that viral infections are a trigger for asthma attacks and estimates suggest 85% of childhood and 60% of adult exacerbations are triggered this way. The most frequent trigger-viruses are the common cold viruses which invade and hijack the infected person’s cell machinery to replicate and survive. Cells can usually detect that they have been invaded and turn on an antiviral defence mechanism; however, the cells of asthmatics do not mount a very effective anti-viral response. There is a real need for better medication to control asthma attacks caused by viral infection and a new strategy might be to target the infected person’s cells rather than the virus, as the virus becomes easily resistant to drugs that directly target it. Dr Aurelie Mousnier from Queens University Belfast was awarded a MRF-Asthma UK fellowship to determine the human proteins essential for common cold virus replication and survival. It is hoped that this research will lay the foundations for new drug candidates that would stop common cold viruses hijacking the cell and prevent its replication in humans. Such developments would be highly significant for the wellbeing of people with asthma.
Dr Amanda Tatler, University of Nottingham
Title: Development of a novel ex vivo “breathing” lung slice model to investigate the dynamic relationship between tidal ventilation, deep inspiration and the development of airway remodelling
The key features of asthma are on-going inflammation in the lung, episodes of chest tightening and difficulty breathing; structural changes in the lungs of people with asthma can reduce lung function over time. These changes are worse in the lungs of severe asthmatics. It is important to understand how these changes occur and investigate new ways of reducing or reversing them. Closure of the airways during an asthma attack can play an important role in the development of these structural changes and this may be caused by the activation of a protein called TGFβ. Dr Amanda Tatler from the University of Nottingham was awarded a MRF-Asthma UK fellowship to investigate the complex relationship between normal breathing, airway closure and activation of TGFβ. In order to do so, Dr Tatler will develop a new model that mimics normal breathing and deep breaths and which closely represents the living, breathing lung. She will use this to investigate the effects of breathing on the activation of TGFβ in order to improve understanding of normal lung biology and its impact on structural change in the lungs of asthmatics. Not only will Amanda’s model support her own asthma research, she will make it available to the wider research community and its uptake will reduce the numbers of animals required to make progress with research on lung diseases.
Dr Rachel Clifford, University of Nottingham
Title: Airway Smooth Muscle (ASM) DNA methylation: A novel target for asthma therapy
It is well known that people with asthma have an increased sensitivity to environmental factors such as pollen and pollution which can trigger an inflammatory response in the lining of the lungs that can lead to changes in airway cells. These cellular changes can then put people at higher risk of triggering asthma symptoms from future contact with environmental factors. Dr Rachel Clifford from the University of Nottingham was awarded a MRF-Asthma UK fellowship to understand how environmental factors change the gene expression by altering markers (methylation) on an individual’s DNA in airway smooth muscle cells leading to tightening of the airways and additional inflammation in the lung. The research is aimed at understanding new ways in which environmental factors drive chronic airway inflammation and the resulting remodelling of the airways and it is hoped that it will lead us closer to a new therapy and understanding whether therapy can reverse asthmatic specific changes in the lung.