IET Syst Biol. 2013 Oct;7(5):126-34. doi: 10.1049/iet-syb.2012.0056.
In many complex regulatory networks with interlinked feedback loops, the simple core circuits are sufficient to achieve the specific biological functions of the whole networks, naturally raising a question: what is the role of the additional feedback loops. By investigating the effect of an additional toggle switch on the auto-activation circuit responsible for competent switch in Bacillus subtilits and on the activator-repressor circuit responsible for cell cycle in Xenopus embryonic, the authors show that the additional toggle switch can elaborate the dynamical behaviour of both circuits. Specifically, the additional toggle switch in B. subtilits does not significantly affect the saturation level of the competent state but can tune the activation threshold (i.e. the minimal stimulus required to switch the system from the non-competent state to the competent state). For the activator-repressor circuit in X. embryonic cell cycle, the additional toggle switch can tune the oscillation frequency but does not change the oscillation amplitude. The proposed detailed results not only provide guidelines to the engineering of synthetic genetic circuits, but also imply a significant fact that additional toggle switches in a complex network are not really redundant but play a role of tuning network functions.
在许多具有相互关联的反馈回路的复杂调控网络中，简单的核心电路足以实现整个网络的特定生物学功能，这自然引发了一个问题：额外的反馈回路的作用是什么。通过研究在枯草芽孢杆菌中负责感受态开关的自动激活电路和在非洲爪蟾胚胎中负责细胞周期的激活物-阻遏物电路上增加一个拨动开关的影响，作者表明，额外的拨动开关可以详细说明这两个电路的动态行为。具体来说，枯草芽孢杆菌中的额外拨动开关不会显著影响感受态状态的饱和度，但可以调整激活阈值（即系统从非感受态状态切换到感受态状态所需的最小刺激）。对于非洲爪蟾胚胎细胞周期中的激活物-阻遏物电路，额外的拨动开关可以调整振荡频率，但不会改变振荡幅度。所提出的详细结果不仅为合成遗传电路的工程设计提供了指导，还暗示了一个重要事实，即复杂网络中的额外拨动开关并不是真正多余的，而是起到了调整网络功能的作用。
