Grant: CIHR Fellowship

According to the Asthma Society of Canada, 3 million Canadians suffer from asthma, 500 of whom die every year. The frequency and severity of asthma is also increasing, placing a heavy burden on our health care system. There is no cure for asthma and scientists do not know what causes it, but we know that excessive contraction in airway muscle (made of cells called smooth muscle) is an important factor. Current treatments for asthma can relax the muscle, but the airways remain sensitive to inhaled irritants. Therefore, we need to understand what makes airway muscle contract excessively. In my proposed research, I will study asthmatic and non-asthmatic airway muscle from human tissues received from the International Institute for the Advancement of Medicine, where human tissue obtained at autopsy is donated for research. Specifically, I will focus on the myosin molecule, which is responsible for muscle contraction. There are 4 kinds of myosin in airway muscle: SM1, SM2, SMA, and SMB. Each kind of myosin forms contractile filaments with different stabilities; for example, filaments formed with SM1 are more stable than those formed with SM2. Because myosin filaments can be disassembled inside airway muscle cells if it is subjected to stretching, such as when we inhale deeply, we would expect that cells which contain more SM1 will contract more in the dynamic environment of a breathing lung because its contractile filaments are more stable. I hypothesize that the SM1:SM2 ratio is disproportionally higher in asthmatic compared with non-asthmatic airway muscle, allowing myosin filaments from asthmatic airway muscle to generate more force. I will study which myosin filaments are in asthmatic and non-asthmatic airway muscle and test their ability to resist stretches. This will help us understand whether there is an intrinsic difference between asthmatic and non-asthmatic airway muscle and help us find new identify targets for drugs to improve the treatment of asthma