Grant: Discovery Grants Program - Individual

My research program focuses on biochemical adaptation to environmental stress. In particular, my lab is interested in the phenomenon of hypometabolism, the ability to enter a state of torpor or dormancy in response to severe environmental challenges (e.g. subzero temperatures, oxygen deprivation, arid conditions) that are not conducive to normal life. We use vertebrate models of hibernation (ground squirrels), freeze tolerance (wood frogs) and anoxia tolerance (turtles) to explore the regulation of metabolism, the adaptations of enzymes and proteins, and the changes in gene expression that both engineer metabolic rate depression and provide long term cell preservation and life extension in hypometabolic states. Not only is this work important for understanding the universal mechanisms of metabolic design in Nature as well as the winter survival strategies of many Canadian animals but it has key potential applications in biomedicine. These include the development of strategies for inducible dormancy and for long term cryopreservation of donor organs removed for transplantation. Goals for continuing and proposed work over the next five years include: (a) investigation of the mechanisms that provide global suppression of gene expression during hypometabolism including histone modifications and the actions of microRNA species in determining whether mRNA transcripts can be translated, (b) identification of stress-responsive transcription factors that are activated during entry into hypometabolism, the suites of downstream genes that they control, and the functions of the selected proteins that are produced, particularly focused on cell preservation mechanisms including antioxidant defense, chaperone proteins, and inhibition of muscle atrophy, (c) exploration of the role played by autophagy - a controlled reduction and recycling of cell contents - to long term survival in hypometabolic states, and (d) control of enzymes and functional proteins via reversible protein phosphorylation to reprioritize metabolic needs and energy use during hypometabolism.