Hibernation timing to reveal mechanisms of rheostasis

ongoing

HiTime is a project about the adjustment of homeostatic set points in physiology. This is known as rheostasis and is of core importance for transitions between physiological states. I seek to develop the concept that a specialised cell type in the hypothalamus, the tanycyte, is the cellular embodiment of a rheostat, and that by understanding the function of the tanycyte, we will gain fundamental insights into hypothalamic control of rheostasis. Since rheostasis is weak in laboratory mice bred to live in constant laboratory environments, new paradigms must be developed. I will therefore investigate tanycyte function in the context of seasonal deep hibernation: the most dramatic example of rheostatic control of energy metabolism in mammals. I will use the golden hamster as the study organism because it has an excellent combination of attributes for pursuing the project aims, from experimental tractability to availability of molecular resources. The study approach will exploit advanced telemetry combined with transcriptomics, metabolomics and neuroimaging to develop an unprecedented “arrow of time” description of changes in tanycyte status in relation to peripheral and central changes in energy metabolites throughout the hibernation. This approach will encompass both long-term rheostatic control of seasonal entry and exit from hibernation, and short-term rheostatic control of torpor-arousal cycles during the hibernation phase. In parallel, I will develop neurogenetic and micro-infusion approaches to allow characterisation of the causal events in rheostatic hibernation control. My career track record gives me an unusual combination of in vivo physiology and bioinformatics skills, which, in combination with my pilot studies establishing new techniques, gives an excellent chance of success despite high ambition. This success will have reciprocal benefits for two major interest areas in physiology with impacts from human obesity research to interplanetary space travel.