Butzin Nicholas C, Hochendoner Philip, Ogle Curtis T, Hill Paul, Mather William H
Department of Physics and ‡Deptartment of Biology, Virginia Polytechnic Institute and State University , Blacksburg, Virginia 24061, United States.
ACS Synth Biol. 2016 Feb 19;5(2):146-53. doi: 10.1021/acssynbio.5b00127. Epub 2015 Nov 12.
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.
刺激对生物振荡的调节是许多现象的根源，包括昼夜节律的维持、神经信号的传播和体节发生。虽然人们已经充分认识到规则的周期性调节可以使振荡器同步，但非周期性（有噪声的）调节也能强有力地使振荡同步。后一种情况可以解释，例如，不规则天气模式对昼夜节律的影响，或者为什么不规则的神经刺激仍然能够可靠地传递信息。一种合成基因振荡器方法已被证明有助于理解周期性信号对生物振荡器的同步作用，它模拟了许多有噪声振荡系统的同步过程。我们同样试图利用合成生物学作为一个平台，来理解非周期性信号如何能使细胞行为产生强烈的相关性。这项研究将有助于更深入地理解我们周围环境甚至体内的波动如何促进细胞间的显著同步。具体而言，我们通过实验和理论研究了大肠杆菌中合成基因振荡器被有噪声刺激同步的情况。利用真实的合成电路，通过微流控和显微镜相结合的方法对这一现象进行了实验研究和验证。相关模型的随机模拟进一步支持了合成基因振荡器能够被非周期性信号强烈同步，尤其是电报噪声。最后，盘基网柄菌中自然振荡器模型和捕食者 - 猎物振荡模型的结果都支持了非周期性同步在合成基因振荡器之外的广泛适用性。
