Date of Award
The surface of the Earth receives 24 hour cycles of light and darkness. Most living things have arisen under these conditions, and have evolved circadian clocks to keep track of time. In Drosophila, the circadian clock comprises the genes Clock (CLK) and Cycle (CYC) which are negatively regulated by the genes Period (PER) and Timeless (TIM). CLK/CYC are transcription factors: their targets include PER/TIM, which accumulate as proteins to repress their own production. Light deactivates PER/TIM proteins, periodically activating CLK/CYC, and causing 24h rhythms of transcription activity. Our lab has previously shown that intestinal stem cells are regulated by the clock during intestinal regeneration. Drosophila, maintained under constant 12h light/12h dark photoperiod, show a rhythmic intestinal stress response, and cell-specific disruption of the clock in different intestinal cell types causes arrhythmic repair and poor survival during damage. This suggests independent cell-autonomous clocks in the intestine coordinate their functions during stress. A central question is whether circadian clocks are coordinated in different tissues, and to what extent are their physiological outputs tissue or cell-autonomous. Using a clock reporter, circadian clocks throughout Drosophila were found to be completely cell autonomous. However, both intestinal damage and aging were found to have attenuating effects on circadian clock function. Food intake was also shown to be able to affect the output of the circadian clock when restricted to a specific time of day. These findings demonstrate the robustness of the circadian system throughout the body.
Bernardon, Nathaniel James, "Testing the Robustness of the Circadian Clock" (2017). Electronic Theses and Dissertations. 7347.
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