SYNTHETIC BIOLOGY. Emergent genetic oscillations in a synthetic microbial consortium.

SYNTHETIC BIOLOGY. Emergent genetic oscillations in a synthetic microbial consortium.
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DOI:
10.1126/science.aaa3794
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发表时间:
2015-08-28
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Bennett MR
Bennett MR
中科院分区:
其他
文献类型:
--
作者:
Chen Y;Kim JK;Hirning AJ;Josić K;Bennett MR

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合成生物学的一个挑战是创造表现出群体水平行为的合作微生物系统。这些系统使用细胞信号传导机制来调节多种细胞类型的基因表达。我们描述了由两种不同的细胞类型组成的合成微生物聚生体的构建-“激活”菌株和“阻遏”菌株。这些菌株产生两种正交的细胞信号分子,其调节跨越两种菌株的合成回路内的基因表达。这两种菌株只有在一起培养时才能产生紧急的种群水平振荡。双应变电路的某些网络拓扑结构在保持鲁棒振荡方面比其他拓扑结构更好。通过多个合作菌株的基因工程来编程群体水平动态的能力,为工程化具有多种细胞类型的复杂合成组织和器官指明了方向。
A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types – an “activator” strain and a “repressor” strain. These strains produce two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way towards engineering complex synthetic tissues and organs with multiple cell types.