Date of Award
Circadian rhythms, Irradiation, JAK/STAT, Stress Response
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Many organisms coordinate behavioural and physiological processes with the Earth’s 24-hour light/dark cycle. This cycle, the circadian rhythm, is anticipated by the circadian clock, a 24-hour timekeeper that is comprised of a transcription-translation feedback loop. The clock regulates the transcription of genes, which can influence the expression of oscillating circadian behaviours, such as sleep/wake. Maintaining tissue homeostasis is an important process, especially in tissues with high cellular turnover rates, such as the intestine. Involved in this intestinal regenerative response is the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway. Damaged cells or exposure to a stressful environment will activate the JAK/STAT pathway to cause increased division of intestinal stem cells and increased differentiation of enteroblasts. Previous work has indicated that intestinal stem cells possess circadian clock activity and the clock regulates intestinal stem cell division during regeneration, suggesting a link between the JAK/STAT regenerative response and the circadian clock. This thesis shows that the circadian clock regulates a time of day dependent damage response in the intestine, and under undamaged conditions, period regulates the JAK/STAT response in the intestine in a non-time dependent manner. Additionally, my research shows that bacterial presence is required to elicit a damage response and axenically raised flies can suppress this response. My research establishes the first link between the circadian clock and the JAK/STAT pathway.
Bachetti, Daniela Bianca, "Testing the Circadian Regulation of the JAK/STAT Signaling Pathway" (2020). Electronic Theses and Dissertations. 8435.