Minimizing Context Dependency of Gene Networks Using Artificial Cells
Minimizing Context Dependency of Gene Networks Using Artificial Cells
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DOI：
10.1021/acsami.8b10029
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发表时间：
2018-09-12
影响因子：
9.5
通讯作者：
Tan, Cheemeng
中科院分区：
文献类型：
--
作者：
Ding, Yunfeng;Contreras-Llano, Luis E.;Tan, Cheemeng
合成基因回路的功能取决于它们的局部化学环境，这些化学环境由周围环境中影响基因转录和翻译的生物分子的类型和浓度所定义。合成基因电路的这种化学背景依赖于工程组件、宿主细胞和环境因素之间的重大而未知的串扰，一直是合成生物学面临的一个持久的挑战。在这里，我们展示了合成基因网络对其细胞外化学环境的敏感性可以被最小化，并且它们设计的功能使用人工细胞变得健壮，人工细胞是使用包裹基因网络的脂质体自下而上设计的合成生物分子隔间。我们的人造细胞在模拟的外部环境中检测、交互和杀死具有不同化学复杂性的细菌。我们的工作使合成基因网络的工程能够最大限度地减少对细胞外化学环境的依赖，并在使用生物启发机制控制合成生物系统的稳健性方面开辟了一个新的前沿。
The functioning of synthetic gene circuits depends on their local chemical context defined by the types and concentrations of biomolecules in the surrounding milieu that influences gene transcription and translation. This chemical-context dependence of synthetic gene circuits arises from significant yet unknown cross talk between engineered components, host cells, and environmental factors and has been a persistent challenge for synthetic biology. Here, we show that the sensitivity of synthetic gene networks to their extracellular chemical contexts can be minimized, and their designed functions rendered robust using artificial cells, which are synthetic biomolecular compartments engineered from the bottom-up using liposomes that encapsulate the gene networks. Our artificial cells detect, interact with, and kill bacteria in simulated external environments with different chemical complexity. Our work enables the engineering of synthetic gene networks with minimal dependency on their extracellular chemical context and creates a new frontier in controlling robustness of synthetic biological systems using bioinspired mechanisms.