Dynamics Of The Circadian Rhythm In Drosophila Melanogaster
The circadian clock drives daily rhythms in many organisms and is a key regulator of diverse physiological functions, including metabolism, the immune system, and sleep. Circadian oscillators also have a variety of interesting dynamical properties, including spontaneous synchronization, entrainment by external stimuli, and temperature compensation of period. In this thesis, we first develop a variety of simple mathematical models, and then use those models to guide experimental work on two different aspects of circadian dynamics in the fruit fly Drosophila melanogaster. In the first set of experiments, we show that a carefully tuned light stimulus can disrupt the coherence of molecular circadian oscillations for several days, and use behavioral data to argue that this could be due to weak coupling between circadian neurons. In the second set of experiments, we use quantitative biochemical measurements to examine the mechanism of temperature compensation of the circadian period. We show that changes in temperature affect molecular oscillations by a simple rescaling of amplitude, and argue that this indicates that separate sub-processes of the circadian clock must be independently temperature compensated. We also investigate the mechanism of circadian temperature entrainment, and present evidence that the heat shock pathway is involved in communicating temperature to the circadian clock.
Circadian rhythms; Systems biology; Temperature compensation
Siggia, Eric Dean
Thorne, Robert Edward; Sethna, James Patarasp
Ph.D. of Physics
Doctor of Philosophy
dissertation or thesis