Grant: Operating Grant

Asthmatics experience wheezing and difficulty breathing because their airways become narrowed. Abnormal contraction of the muscle in the airways is one of the major causes of the airway narrowing seen during an asthma attack. Although we know that airway muscle is involved in acute life-threatening asthma attacks, the exact mechanism of how this occurs is not clear. Some recent studies suggest that the muscle is abnormal in asthmatics. However, how the muscle abnormality results in excessive narrowing of the airway is yet to be determined. A major obstacle to our understanding of the abnormal behavior of asthmatic airway muscle is the lack of knowledge of the basic biochemical mechanism of contraction in normal airway muscle. It is clear that if we do not know how normal muscle works, we will not be able to determine what is abnormal in the asthmatic airway muscle and fix the defect. In this application we propose to study both the normal behavior and biochemical composition of airway muscle and the changes that occur in asthma. We will use the high-resolution imaging technique of electron microscopy to examine the protein structure inside the muscle cells and relate the changes in the structure to the changes in the mechanical and biochemical properties of the cells. The results of our research will advance our understanding of the fundamental process of muscle contraction and how this process could be altered in asthma. The research will also lead to identification of targets inside the muscle cells that could be useful for better drug treatments for asthma. Over 3 million Canadians suffer from asthma and the disease kills 20 children and 500 adults every year in Canada. The incidence of asthma is increasing in Canada. Every year in Canada there are 146,000 emergency room visits due to asthma attacks and over $12 billion is spent on asthma in Canada. A better treatment for asthma will go a long way in reducing the cost to society in the long run.