Marching along to an Offbeat Drum: Entrainment of Synthetic Gene Oscillators by a Noisy Stimulus

Modulation of biological
oscillations by 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, an aperiodic
(noisy) 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 gene oscillator approach
has already proven to be useful in understanding the entrainment of
biological oscillators by periodic signaling, mimicking the entrainment
of a number of noisy oscillating systems. We similarly seek to use
synthetic biology as a platform to understand how aperiodic 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 among our cells.
Specifically, we investigate experimentally and theoretically the
entrainment of a synthetic gene oscillator in E. coli by a noisy stimulus. This phenomenon was experimentally studied
and verified by a combination of microfluidics and microscopy using
the real synthetic circuit. Stochastic simulation of an associated
model further supports that the synthetic gene oscillator can be strongly
entrained by aperiodic signals, especially telegraph noise. Finally,
widespread applicability of aperiodic entrainment beyond the synthetic
gene oscillator is supported by results derived from both a model
for a natural oscillator in D. discoideum and a model
for predator–prey oscillations.