Grant: Discovery Grants Program - Individual

Sensitization to airborne allergens such as pollen, pet dander and cockroaches affects 20-25% of Canadians and is associated with a range of inflammatory disorders including asthma, hypertension, and respiratory infection. The long-term objective of my research is to understand how the biochemical properties of allergenic proteins contribute to these negative health outcomes. The ability to bind lipid cargoes is over-represented among allergens, suggesting that co-delivery of these exogenous compounds may play a role. Building on these observations, my Highly-Qualified Personnel (HQP) trainees and I will pursue three linked objectives exploring the fundamental biochemical mechanisms through which allergen-mediated lipid delivery impacts respiratory health at the molecular level. In previous works I showed that allergens from cockroach (Bla g 1), cat (Fel d 7) and dog (Can f 1) can deliver exogenous lipids directly into cellular membranes, damaging their structure. In objective 1, we will characterize the immunological impact of allergen-induced cellular damage. Using in vitro and ex vivo model systems we will correlate allergen-mediated membrane disruption with the generation/release of pro-inflammatory damage-associated signalling molecules and lipid mediators, providing insight into the role of lipid-binding allergens in the development of respiratory inflammatory disorders at the molecular level. In objective 2, we will examine the ability of lipid-binding allergens to disrupt the pulmonary surfactant: a lipid-protein complex which coats the inside of the lungs and facilitates respiratory function and immune defense. Analytical and biophysical chemistry approaches will be used to monitor the impact of respiratory allergens and their associated lipid ligands on the structure/function of model surfactant monolayers, providing an additional avenue through which these proteins can influence respiratory health. In objective 3, we will test whether lipid-binding allergens can increase the bioavailability of environmental contaminants. Using analytical chemistry approaches we will assess the ability of lipid-binding allergens to bind perfluoroalkyl substances (PFAS) - a family of ubiquitous immunotoxic environmental contaminants - and facilitate their delivery into lipid bilayers and surfactant monolayer systems, potentially enhancing the bioavailability and immunogenicity of both compounds. The proposed research will provide novel perspectives on the role of lipid-binding allergens in the development of allergic/inflammatory disorders and their associated environmental health disparities. This research emphasizes the use of biophysical and cell-based approaches to understand fundamental processes in human health: providing cross-disciplinary training opportunities for HQPs in line with St. Francis Xavier's strategic focus on integrative health studies while contributing to NSERC's mandate to support cutting-edge research in the natural sciences.