We study how genes control life processes in homeostasis and organismic responses to extreme physical chemical conditions.
Low temperature (hypothermia) and reduced oxygen (hypoxia) pervasively affect cellular metabolism and physiology, decelerate organismic biological time, and trigger instinctive animal behaviors. Many species in nature have evolved unique traits to respond and adapt to severe hypothermia/hyperthermia/hypoxia. In humans, tissue injuries caused by ischemia-reperfusion can be alleviated by therapeutic hypothermia, now widely used in clinics for patients with ischemic disorders, including stroke and heart attack. Mechanisms of therapeutic hypothermia and the genetic basis underlying innate hypoxia/hypothermia tolerance remain largely unknown.
We use 1) genetically tractable C. elegans mutants isolated from large-scale screens with abnormal behavioral and extremophile-like phenotypes and 2) Mangrove Killifish, the only known self-fertilizing vertebrate with genetics similar to that of C. elegans and known extreme physiological phenotypes, as discovery tools. We also culture mammalian neural stem cells ex vivo from hibernating ground squirrels to understand cellular intrinsic tolerance of hypoxia/hypothermia. Genes identified from such model systems encode proteins of unprecedented properties that define novel mechanisms underlying cytoprotection, cellular organelle dynamics and organismic homeostasis in physiology and behaviors.
Knowledge learned from extreme physiology and principles of biological adaptation has potential applications in developing novel means of cytoprotection, organ transplantation, reversible cryo-preservation and therapeutics to treat metabolic, neurological and ischemic disorders.