title: Marching along to an Offbeat Drum: Entrainment of Synthetic Gene Oscillators by a Noisy Stimulus.
abstract: 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.
authors.affiliation: Department of Physics and ‡Deptartment of Biology, Virginia Polytechnic Institute and State University , Blacksburg, Virginia 24061, United States.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Butzin
authors.affiliation: Department of Physics and ‡Deptartment of Biology, Virginia Polytechnic Institute and State University , Blacksburg, Virginia 24061, United States.
authors.forename: Philip
authors.initials: P
authors.lastname: Hochendoner
authors.affiliation: Department of Physics and ‡Deptartment of Biology, Virginia Polytechnic Institute and State University , Blacksburg, Virginia 24061, United States.
authors.forename: Curtis T
authors.initials: CT
authors.lastname: Ogle
authors.affiliation: Department of Physics and ‡Deptartment of Biology, Virginia Polytechnic Institute and State University , Blacksburg, Virginia 24061, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Hill
authors.affiliation: Department of Physics and ‡Deptartment of Biology, Virginia Polytechnic Institute and State University , Blacksburg, Virginia 24061, United States.
authors.forename: William H
authors.initials: WH
authors.lastname: Mather
mesh_terms: D001683:Biological Clocks; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins
keywords: aperiodic signal; entrainment; oscillators; random signal; synthetic biology; systems biology