Considerations for using integral feedback control to construct a perfectly adapting synthetic gene network
Considerations for using integral feedback control to construct a perfectly adapting synthetic gene network
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DOI：
10.1016/j.jtbi.2010.07.034
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发表时间：
2010-10-21
影响因子：
2
通讯作者：
McMillen, David R.
中科院分区：
文献类型：
--
作者：
Ang, Jordan;Bagh, Sangram;McMillen, David R.
控制理论家和工程师早就知道，积分反馈控制导致，并且是必要的，“完美”适应阶跃输入扰动在大多数系统。因此，在合成基因网络中实现这种鲁棒控制策略是一个有吸引力的前景。然而，遗传调控网络的性质（密度依赖性动力学和容易达到饱和的分子信号）意味着这样的装置的设计和构造不是简单的。在这项研究中，我们提出了一个通用的两个启动子的遗传调控网络的目的表现出完美的适应，我们的治疗突出了固有的挑战，在实施遗传积分控制器。我们还提出了一个具体实现这两个启动子网络，“构建”使用常见的部分从细菌大肠杆菌的数值案例研究。我们说明了优化这个网络的瞬态响应的可能性，通过类比线性，自由阻尼谐振子。最后，我们讨论了扩展这两个启动子网络的比例积分控制器和三个启动子网络能够完美的适应条件下，一阶蛋白质去除效果，否则会破坏适应。(c)2010爱思唯尔有限公司版权所有。
It has long been known to control theorists and engineers that integral feedback control leads to, and is necessary for, "perfect" adaptation to step input perturbations in most systems. Consequently, implementation of this robust control strategy in a synthetic gene network is an attractive prospect. However, the nature of genetic regulatory networks (density-dependent kinetics and molecular signals that easily reach saturation) implies that the design and construction of such a device is not straightforward. In this study, we propose a generic two-promoter genetic regulatory network for the purpose of exhibiting perfect adaptation; our treatment highlights the challenges inherent in the implementation of a genetic integral controller. We also present a numerical case study for a specific realization of this two-promoter network, "constructed" using commonly available parts from the bacterium Escherichia coli. We illustrate the possibility of optimizing this network's transient response via analogy to a linear, free-damped harmonic oscillator. Finally, we discuss extensions of this two-promoter network to a proportional-integral controller and to a three-promoter network capable of perfect adaptation under conditions where first-order protein removal effects would otherwise disrupt the adaptation. (c) 2010 Elsevier Ltd. All rights reserved.