Is Lyn tyrosine kinase a predictor of severe, persistent multi-trait asthma and allergy?

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Asthma is a major health problem in Australia affecting over 10% of the population at any time, and more than 25% of the population at one stage in their lives. Although the public perception is that asthma treatments have improved management of the disease, more than 700 people die from severe asthma each year and hospitalisation from exacerbation (sudden worsening) is one of the most costly components of the health care burden in Australia and most developed countries. Currently there are no molecular markers that can predict who will get severe asthma and there are no specific treatments to reverse severe exacerbations. This project will use advanced molecular biology methods to examine whether a molecule called Lyn may be important. The Lyn tyrosine kinase is a member of a family of genes that participate in transmitting information across the cell membrane. This enzyme is expressed in blood cells, and is involved in mechanisms pertaining to infection, immunity and allergic responses. To further our understanding of the role of this enzyme in the context of the whole animal, we have generated mice that are unable to make Lyn protein (Lyn-deficient mice). In animal models of asthma we know that if Lyn is not functioning, severe and persistent asthma develops. We have also made preliminary studies that suggest that Lyn does not work properly in people who have been admitted to the emergency ward with life threatenting asthma. In this study we will examine in detail the role that Lyn plays in asthma and allergy, and we intend to identify the pathways that give rise to asthma in Lyn-deficient mice. We will also investigate our hypothesis that Lyn activity may be reduced or disregulated in patients with asthma and allergy. This research should lead to better predictive markers for severe asthma and also to improved and specific treatments.