Entrainment of Synthetic Gene Oscillators By a Noisy Stimulus

Modulation of biological oscillations by external stimuli lies at the root of many phenomena, including maintenance of circadian rhythms, propagation of neural signals, and somitogenesis. While it is well established that regular periodic modulation can entrain an oscillator, a curious phenomenon is that a noisy (rugged) modulation can also robustly entrain oscillations. This latter scenario may describe, for instance, the effect of irregular weather patterns on circadian rhythms, or why irregular neural stimuli can still reliably transmit information. A synthetic biology approach has already proven useful in understanding the entrainment of oscillators by periodic signaling, which can mimic the response of a number of noisy oscillating systems: cell cycles,
NF-kB response, etc. We similarly seek to use synthetic biology as a platform to understand how aperiodic (random) signals can strongly correlate the behavior of cells. This study should lead to a deeper understanding of how fluctuations in our environment and even within our body may promote substantial synchrony between our cells. We investigate experimentally and theoretically the entrainment of an ensemble of synthetic gene oscillators by a noisy stimulus. Stochastic simulations suggested that a synthetic gene oscillator would be strongly entrained by two aperiodic signals: telegraph noise and phase noise. This simulation-based prediction was tested by a combination of microfluidic and microscopy using a real synthetic circuit in Escherichia coli. We use delayed feedback models to analyze these cells. We show that cells are entrained by two noisy signals: telegraph and phase noise. Cells are entrained when either signal period or amplitudes are varied.