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

Asthma is a complex respiratory and immune disease. The environment and its interaction with the genetic make-up of the host determine the onset, progression and severity of the lung inflammatory response associated with asthma. The limited success in identifying genes regulating asthma is not only due to the inherent genetic complexity of the disease, but also to the very limited number of genetic models suitable for studying this complex disease. By taking advantage of a new mouse model of asthma together with a unique genetic platform, we have shown that genes conferring susceptibility to asthma are tractable. We have identified several mouse candidate chromosomal regions that coincide with asthma susceptibility loci identified in humans, indicating that our approach will yield genes with a high probability of being relevant to the development of asthma. In this proposal our initial efforts will be directed to identify asthma susceptibility genes within a chromosome region, which has gone undetected in previous studies, because 1) the region shows the stronger effect and therefore will be more easily amenable to gene identification, 2) the region harbors several candidate genes that may point to new insight into the mechanisms of asthma susceptibility. A second aspect of the proposal involves an understanding of the various aspects of asthma and will aim to address the question of whether the same genes and pathways underlie allergic asthma and atopy, a heritable trait that results in higher than average expression of immunoglobulin E (a protein involved in allergy). We anticipate that the proposed studies will provide us a better understanding of the molecular mechanisms underlying asthma and will enable the identification of new treatments and targets for new drugs.