The ability of wood frogs, Rana sylvatica¸ to survive freezing and clinical death during harsh northern winters necessitates well-grounded mechanisms for managing extreme anoxia, dehydration, and reperfusion damage. These stresses are major instigators of pathogenesis yet to be overcome by humans. Contemporary efforts in the field are focused on interrogating stress-specific mediators that play a cytoprotective role in vital tissues such as skeletal muscle, providing valuable information to the biomedical community. Herein, the potential role of DNA and histone lysine methylation enzymes are examined in wood frog skeletal muscle in response to 24 h anoxia and 40% dehydration independently, and recovery from both stresses. This thesis demonstrates a condition-specific response of many epigenetic methylation regulators, highlighting some conserved similarities in comparison to prior freeze-thaw models. These findings support an integral role of epigenetic regulators in survival of hypometabolic stresses, most prominently during recovery stages. These cytoprotective effects are likely attributed to functional roles in transcriptional suppression during hypometabolism and activation during recovery, but also alternative roles based on known interactions with regulators of the cell cycle and repair pathways.iii
ACKNOWLEDGEMENTSTo everyone at the Storey Lab, and to the extended fam at Carleton, thank you so much for all the great memories over the years! Every single one of you has been a joy to meet, and I will forever cherish the time we spent together grinding away in the office, at the bench, and furiously 'grading' at Ollie's. Ken and Jan, you took a chance on a rusty headbanger that had little prior lab experience and provided me with a hopeful new direction in life by accepting me into your lab. It is inspiring the number of lives you have positively impacted with your wisdom and guidance, as is this welcoming and diverse space for research you have created, which has felt like a safehouse from the storms of life. You have given me the means to nurture my scientific abilities, and facilitated my journey to being a productive member of society that is proud of the work I do. You two are truly legendary humans in so many ways. I'd also like to give a special thanks to my mentors Sam and Tighe. Your dedication and enthusiasm for helping others, and for this work, have been contagious. You have awoken a beast-of-research in me, while taming my technical and analytic skills into something of finesse that I am confident in. You have shown me how to have a critical eye for research, and what it takes to be a good scientist in this world, but also how fun and rewarding it can be. I will always hold your impromptu lessons close to me and strive to be more like you in my work. To the lads (Mackenzie, Kupa, Wale, Saif, and Gurjit), and especially the 'lunch ladies' (Aakriti, Aline, Anchal, Maire, Rasha, and Sarah), I would not be where I am today without you. Your kindness and guidance have been monumental to my success in...