To survive extreme environmental stresses such as the deep cold, oxygen deprivation, and dehydration, an impressive array of organisms have evolved to radically depress their metabolism, often lowering it to just 5-20% of normal rates. The Storey Lab studies the biochemical adaptations and molecular mechanisms that allow animals to suspend physiological functions for prolonged periods of metabolic arrest (such as during whole-body freezing) and still be able to emerge unscathed when favourable conditions return. Our research has potential medical applications for extending transplant organ preservation times by applying the lessons we are learning from Nature to further improve human therapeutics.
We have found multiple mechanisms that contribute to global metabolic rate depression and our new research can be divided into three main themes:
Reversible phosphorylation and post-translational modification of key regulatory enzymes and functional proteins (e.g. glycolytic enzymes, antioxidant enzymes, kinases, ribosomal factors) to produce less active enzyme forms.
Differential activation of select transcription factor networks and signal transduction cascades during entry into or arousal from a hypometabolic state to regulate and stabilize protein turnover.
Epigenetic mechanisms of gene silencing (e.g. DNA methylation, histone modification, microRNA regulation) that mediate chromatin accessibility and post-transcriptional controls of stress-inducible genes.