Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Asthma afflicts 12% of children and 6% of adults in Canada and has a total annul economic burden exceeding $750 million. The rate and morbidity of asthma has risen steadily in the past 25 years despite significantly higher use of pharmacological therapies; this indicates that much greater insight to the molecular and cellular processes that drive the progressive worsening of asthma in individual patients is needed. Understanding of the disease process will provide clues for designing drugs to inhibit, perhaps even reverse, disease progression. Our studies will investigate how a subclass of receptors, known as GPCRs, on airway smooth muscle cells are controlled by discrete membrane structures called caveolae and the proteins that are responsible for their organization.GPCRs are important in asthma, as they regulate muscle contraction and proliferation, key processes underlying acute asthma attacks and the progressive worsening of the disease. We will focus on how interactions of caveolae with a protein complex called the dystrophin-glycoprotein complex control signals generated from a specific GPCR called M3R and how these are integrated to induce smooth muscle cell responses associated with asthma.We plan a broad translational research approach using cell systems and biochemical techniques to underpin physiological studies using transgenic mouse models. Better understanding of how this unique system works, holds good promise for designing new and more effective therapeutic interventions for asthma.