Waking the sleeping dragon : molecular insights into the hibernation of the central bearded dragon

One of the most profound adaptive strategies employed by animals in response to changes in environmental conditions is hibernation. Hibernation is an extended state of hypometabolism and dormancy induced to survive the low food availability and high physiological stress associated with winter. During the long periods of dormancy, hibernators experience changes in core biological processes, including drastic reductions in basal metabolic rate, core body temperature, oxygen consumption, heart rate and brain activity. Stress response pathways are also modulated to mitigate physiological challenges that would otherwise prove lethal to the animal. Modulation of these responses requires tightly controlled regulatory processes. While hibernation is a common response utilised by diverse lineages of animals, molecular investigations into this phenomenon have primarily focused on mammalian systems. In this thesis, I investigated the molecular mechanisms involved in the hibernation of the Australian central bearded dragon (Pogona vitticeps) using high-throughput sequencing technologies. The transcriptomic and proteomic changes in three tissues; brain, heart and skeletal muscle, during hibernation and at two time points post-arousal were examined. Hibernation was associated with the induction of common and tissue-specific stress response pathways in addition to the modulation of regulatory processes. I studied the role of microRNAs (miRNA) in mediating the changes in gene expression that are characteristic of the three tissues during hibernation and four days post-arousal. Cellular metabolism and neuroprotection of the brain emerged as key pathways under miRNA-mediated regulation. The DNA methylation dynamics in brain and skeletal muscle during hibernation and at two time points post-arousal were also examined. Alterations in DNA methylation were associated with changes in gene expression that lead to increased neuroprotection of the brain and a reduced potential for atrophy in skeletal muscle. Collectively, the data presented in this thesis shows that the precise interplay of multiple gene regulatory mechanisms is crucial in modulating the large-scale changes in cellular physiology and function observed in hibernating bearded dragons. Furthermore, the data presented bridges the gap between mammalian and reptilian hibernation and suggests they are more similar than previously thought