合成生物学中的控制系统及细胞命运重编程案例研究
Control systems for synthetic biology and a case-study in cell fate reprogramming
AI总结：
本文探讨了合成生物学中生物分子控制系统的应用，通过细胞命运重编程案例展示了反馈和前馈控制策略在细胞调控中的作用及未来研究方向。
摘要：
本文综述了控制系统工程在合成生物学中的应用，受细胞治疗和再生医学中细胞命运重编程等应用的启发。在这些和其他应用中，一个普遍的问题是准确控制细胞内特定调控因子浓度的能力，尽管存在环境不确定性和扰动。本文描述了这些扰动的来源以及它们如何影响待控制的生物分子『系统』的动态。随后介绍了多种生物分子控制实现方法，以实现系统输出对扰动的鲁棒性，并将其分为反馈和前馈控制架构。虽然今天可以在计算机上实现复杂的控制律，但它们不一定能通过生物分子过程在细胞内实现。这一事实限制了可行的控制律集合为那些可通过合成生物学工程实现的生物分子过程。在回顾生物分子反馈和前馈控制实现后，本文展示了这些控制策略在细胞命运重编程中的应用。在此背景下，需要在细胞内将主调控因子控制在特定水平，以将皮肤细胞重编程为多能干细胞。文章最后强调了生物分子控制设计面临的持续挑战和未来研究方向。
英文摘要：
This paper gives an overview of the use of control systems engineering in synthetic biology, motivated by applications such as cell therapy and cell fate reprogramming for regenerative medicine. A ubiquitous problem in these and other applications is the ability to control the concentration of specific regulatory factors in the cell accurately despite environmental uncertainty and perturbations. The paper describes the origin of these perturbations and how they affect the dynamics of the biomolecular ``plant'' to be controlled. A variety of biomolecular control implementations are then introduced to achieve robustness of the plant's output to perturbations and are grouped into feedback and feedforward control architectures. Although sophisticated control laws can be implemented in a computer today, they cannot be necessarily implemented inside the cell via biomolecular processes. This fact constraints the set of feasible control laws to those realizable through biomolecular processes that can be engineered with synthetic biology. After reviewing biomolecular feedback and feedforward control implementations, mostly focusing on the author's own work, the paper illustrates the application of such control strategies to cell fate reprogramming. Within this context, a master regulatory factor needs to be controlled at a specific level inside the cell in order to reprogram skin cells to pluripotent stem cells. The article closes by highlighting on-going challenges and directions of future research for biomolecular control design.
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