You snooze, you win: torpor as a model of resilience (360G-Wellcome-308526_Z_23_Z)

When deprived of food, daily heterotherms such as mice enter torpor - a protective state of reduced body temperature, oxygen consumption, and heart rate akin to a brief hibernation. Using DREADDs to activate neurons in the preoptic area of the hypothalamus (POA), I can trigger ’synthetic torpor’ in mice, and, intriguingly, in rats (a species that does not naturally enter torpor). This fellowship explores translational applications of biomimetic synthetic torpor, to: • Investigate the organ-protective properties of synthetic torpor. Building on pilot data, I will determine whether synthetic torpor in rats protects when applied after cardiac ischaemia-reperfusion injury, and define the mechanisms underlying this protection, including the dependence on temperature change, the vagus nerve, and mitochondrial modulation. • Characterise the interaction between torpor and inflammation. My pilot data that indicates torpor modulates the inflammatory response to LPS. This package will determine whether torpor and synthetic torpor are protective in an in-vivo model of mouse sepsis. • Transcriptomic approach to translational torpor. I will use gene expression profiling in the hypothalamus to explore why mice naturally enter torpor, but rats and humans do not. This will contribute to our understanding of whether we might one day target conserved mechanisms in humans.