Nelson Edward M, Kurz Volker, Perry Nicolas, Kyrouac Douglas, Timp Gregory
Department of Biological Sciences and Electrical Engineering, University of Notre Dame , Notre Dame, Indiana 46556, United States.
ACS Synth Biol. 2014 May 16;3(5):286-97. doi: 10.1021/sb400052f. Epub 2013 Oct 23.
Noise is inherent to single cell behavior. Its origins can be traced to the stochasticity associated with a few copies of genes and low concentrations of protein and ligands. We have studied the mechanisms by which the response of noisy elements can be entrained for biological signal processing. To elicit predictable biological function, we have engineered a gene environment that incorporates a gene regulatory network with the stringently controlled microenvironment found in a synthetic biofilm. The regulatory network leverages the positive feedback found in quorum-sensing regulatory components of the lux operon, which is used to coordinate cellular responses to environmental fluctuations. Accumulation of the Lux receptor in cells, resulting from autoregulation, confers a rapid response and enhanced sensitivity to the quorum-sensing molecule that is retained after cell division as epigenetic memory. The memory of the system channels stochastic noise into a coordinated response among quorum-sensing signal receivers in a synthetic biofilm in which the noise diminishes with repeated exposure to noisy transmitters on the input of a signaling cascade integrated into the same biofilm. Thus, gene expression in the receivers, which are autonomous and do not communicate with each other, is synchronized to fluctuations in the environment.
噪声是单细胞行为所固有的。其起源可追溯到与少量基因拷贝以及低浓度蛋白质和配体相关的随机性。我们研究了将噪声元件的响应用于生物信号处理的机制。为了引发可预测的生物学功能，我们构建了一种基因环境，该环境整合了一个基因调控网络以及在合成生物膜中发现的严格控制的微环境。该调控网络利用了lux操纵子群体感应调控元件中发现的正反馈，用于协调细胞对环境波动的反应。由于自动调节导致细胞中Lux受体的积累，赋予了快速反应，并增强了对群体感应分子的敏感性，该分子在细胞分裂后作为表观遗传记忆得以保留。系统的记忆将随机噪声引导至合成生物膜中群体感应信号接收器之间的协调反应，在该生物膜中，随着对整合到同一生物膜中的信号级联输入上的噪声发射器的反复暴露，噪声会逐渐减弱。因此，彼此自主且不相互通信的接收器中的基因表达与环境波动同步。
