Circadian Control of a Time-Dependent Damage Response in Drosophila melanogaster

Shahd Haddad, University of Windsor


Circadian rhythms are physiological and behavioural processes that cycle in a 24-hour period, and they are driven by the circadian clock. The circadian clock is an internal molecular timekeeper that consists of a transcription-translation feedback loop, which controls the expression of many different genes, including ones involved in fasting-feeding and sleep-wake cycles, in a circadian rhythmic manner. The Drosophila intestinal epithelium is constantly renewed by intestinal stem cells (ISCs) and, during regeneration, Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signalling drives increased ISC division and differentiation. Our lab has previously shown that regeneration is gated by the circadian clock. I therefore hypothesised that the time of intestinal damage affects the regeneration response and used a dGFP reporter of JAK/STAT activity as a readout. Two acute damage assays that allow the control of damage timing were developed: chemical feeding and genetically-induced apoptosis of epithelial cells. In both of these assays, JAK/STAT activation in response to damage is reduced in period mutants (per01). In addition, my thesis shows that the JAK/STAT activity exhibits a time-dependent rhythm in response to apoptosis, and that this rhythm is absent in per01 mutants. My research further shows that the JAK/STAT components are expressed at significantly higher levels in wildtype compared to per01 suggesting a per-dependent transcriptional mechanism regulating JAK/STAT signalling. Overall, my research shows that the JAK/STAT pathway in the midgut is regulated by the circadian clock during regeneration.