A synthetic biology approach to understanding biological oscillations: Developing a genetic oscillator for Escherichia coli

Our goals are to construct a simple genetic clock that will stably oscillate in Escherichia coli and to identify the design principles and parameters responsible for oscillations. We previously described a simple genetic circuit of linked activator and repressor operons that produced damped oscillations. Here, we altered the repression of the activator operon and identified an oscillator that produces improved oscillations over our initial system. We also explored mathematical models of the oscillator. Toy models were used to investigate the behaviors that may be obtained from our clock circuitry. Depending on parameters, the circuitry produced a wide array of oscillatory systems, including sinusoidal and relaxation oscillators. We also attempted to explicitly model all known interactions that affect the oscillator, producing a 32-dimensional ODE model. This model can produce results similar to those obtained in experiments, and we have begun attempts to fit experimental data to the model.