Laboratoire Matière et Systèmes Complexes, UMR 7057 CNRS & Université Paris Diderot, 10 rue Alice Domon et Léonie Duquet, 75013, Paris, France.
Inria Saclay-Ile-de-France and Université Paris Saclay, 1 rue Honoré d'Estienne d'Orves, Bâtiment Alan Turing, Campus de l'Ecole Polytechnique, 91120, Palaiseau, France.
Nat Commun. 2017 Nov 17;8(1):1671. doi: 10.1038/s41467-017-01498-0.
Cybergenetics is a novel field of research aiming at remotely pilot cellular processes in real-time with to leverage the biotechnological potential of synthetic biology. Yet, the control of only a small number of genetic circuits has been tested so far. Here we investigate the control of multistable gene regulatory networks, which are ubiquitously found in nature and play critical roles in cell differentiation and decision-making. Using an in silico feedback control loop, we demonstrate that a bistable genetic toggle switch can be dynamically maintained near its unstable equilibrium position for extended periods of time. Importantly, we show that a direct method based on dual periodic forcing is sufficient to simultaneously maintain many cells in this undecided state. These findings pave the way for the control of more complex cell decision-making systems at both the single cell and the population levels, with vast fundamental and biotechnological applications.
控制论是一个新兴的研究领域，旨在实时远程控制细胞过程，以利用合成生物学的生物技术潜力。然而，到目前为止，只有少数几个遗传电路得到了测试。在这里，我们研究了多稳态基因调控网络的控制，这种网络在自然界中普遍存在，在细胞分化和决策中起着关键作用。我们使用一个计算机反馈控制回路，证明了双稳态遗传振子开关可以在其不稳定平衡点附近长时间动态地保持。重要的是，我们表明，基于双周期强迫的直接方法足以同时将许多细胞维持在这种不确定状态。这些发现为在单细胞和群体水平上控制更复杂的细胞决策系统铺平了道路，具有广泛的基础和生物技术应用。
