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Engineering robust and tunable spatial structures with synthetic gene circuits

机译:使用合成基因电路设计鲁棒且可调的空间结构

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摘要

Controllable spatial patterning is a major goal for the engineering of biological systems. Recently, synthetic gene circuits have become promising tools to achieve the goal; however, they need to possess both functional robustness and tunability in order to facilitate future applications. Here we show that, by harnessing the dual signaling and antibiotic features of nisin, simple synthetic circuits can direct Lactococcus lactis populations to form programmed spatial band-pass structures that do not require fine-tuning and are robust against environmental and cellular context perturbations. Although robust, the patterns are highly tunable, with their band widths specified by the external nisin gradient and cellular nisin immunity. Additionally, the circuits can direct cells to consistently generate designed patterns, even when the gradient is driven by structured nisin-producing bacteria and the patterning cells are composed of multiple species. A mathematical model successfully reproduces all of the observed patterns. Furthermore, the circuits allow us to establish predictable structures of synthetic communities and controllable arrays of cellular stripes and spots in space. This study offers new synthetic biology tools to program spatial structures. It also demonstrates that a deep mining of natural functionalities of living systems is a valuable route to build circuit robustness and tunability.
机译:可控的空间图案化是生物系统工程的主要目标。最近,合成基因电路已成为实现该目标的有前途的工具。但是,它们需要兼具功能的鲁棒性和可调性,以便于将来的应用。在这里,我们表明,通过利用乳链菌肽的双重信号传导和抗生素特性,简单的合成电路可以指导乳酸乳球菌种群形成编程的空间带通结构,该结构不需要微调,并且可以抵抗环境和细胞环境的干扰。虽然健壮,但模式是高度可调的,其带宽由外部乳链菌肽梯度和细胞乳链菌肽免疫力指定。此外,即使梯度是由产乳链菌肽的结构化细菌驱动,并且图案化细胞由多种物种组成,电路也可以引导细胞一致地产生设计的图案。数学模型成功地再现了所有观察到的模式。此外,电路允许我们建立合成群落的可预测结构以及空间中细胞条纹和斑点的可控阵列。这项研究提供了新的合成生物学工具来编程空间结构。它还表明,对生命系统自然功能的深度挖掘是建立电路鲁棒性和可调性的宝贵途径。

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