Design Principles and Coupling of Biological Oscillators
One of the main challenges that biological oscillators face at the cellular level is maintaining coherence in the presence of molecular noise. Mechanisms of noise resistance have been proposed, however the findings are sometimes contradictory and not universal. Another challenge faced by biological oscillators is the proper timing of cellular events and effective distribution of cellular resources when there is more than one oscillator in the same cell. Biological oscillators are often coupled, however, the mechanisms and extent of these couplings are poorly understood. In this thesis, I describe three separate yet interconnected projects in an attempt to understand these biophysical phenomena.
I show that slow DNA unbinding rates are important in titration-based oscillators and can mitigate molecular noise. Multiple DNA binding sites can also increase the coherence of the oscillations through protected states, where the DNA binding/unbinding between these states has little effect on gene expression. I then show that experimental titration-based oscillator in budding yeast is innately coupled to the cell cycle. The oscillator and the cell cycle show 1:1 and 2:1 phase locking similar to what has been observed in natural systems. Finally, by studying the relationship between the circadian redox rhythm and genetic circadian clock in plants I show how perturbation of one of the coupled oscillators can be transformed into a reinforcement signal for the other one via a balanced network architecture.
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