Grant: Discovery Grants Program - Individual

Glucose is the most abundant monosaccharide in the cell. It is chemically reactive and can undergo an undesired reaction with different classes of biomolecules, such as amino acids and proteins, affecting their physicochemical properties and potentially their biological functions. Known as non-enzymatic glycation, this reaction generally occurs at a slow rate and is a major component of the aging process in living organisms. A broad range of physiological complications, such as diabetes, cataracts, and neurodegenerative and cardiovascular diseases has been linked to non--enzymatic glycation. Previous studies have shown that the reaction accelerates under oxidative stress conditions. Biometals, such as iron and copper, can induce oxidation and facilitate oxidative reactions. Some studies have, therefore, postulated that selective decreasing of endogenous metal levels may have a controlling effect on non-enzymatic glycation. Several classes of natural compounds that react with the excess amounts of prooxidant metals were found to have an inhibitory effect on undesired glycation in humans; however, the underlying mechanisms are not fully understood. The overarching goal of this research program is to develop methods for quantitative study of non-enzymatic glycation in biological systems. Through this program, we will aim to identify new biomarkers that can help us better understand the glycation reaction at a systemic level. In the present funding period, an experimental model will be developed for the study of non-enzymatic glycation in vitro with a focus on low molecular weight metabolites (objective 1). Analytical methods will be created and tested for comprehensive profiling and targeted quantitation of major glycation products in biological samples (objective 2). A multiplex assay will be subsequently developed and validated to monitor the rate and extent of non-enzymatic glycation in the presence and absence of excess prooxidant metals in a cell culture model (objective 3). These achievements will be valuable to dietetics, aging research, diagnosis, and understanding of glycoxidative stress-related disorders and their molecular pathogenesis. This research program incorporates new methods and hypotheses and presents an opportunity for training undergraduate and graduate students. Strategies to bring discoveries made herein to market will be developed through partnership with Canadian industry leaders in health food technologies and molecular diagnostics. This research program will have a significant impact on our knowledge of non-enzymatic glycation, its numerous physiological consequences, and on Canada's global leadership in technology development in the field of natural sciences.