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使用基因裂解电路对大肠杆菌细胞群体进行控制的系统方法。

Systematic approach to Escherichia coli cell population control using a genetic lysis circuit.

作者信息

Hsu Chih-Yuan, Yu Tsu-Chun, Lin Ling-Jiun, Hu Rei-Hsing, Chen Bor-Sen

出版信息

BMC Syst Biol. 2014;8 Suppl 5(Suppl 5):S7. doi: 10.1186/1752-0509-8-S5-S7. Epub 2014 Dec 12.

Abstract

BACKGROUND

Cell population control allows for the maintenance of a specific cell population density. In this study, we use lysis gene BBa_K117000 from the Registry of Standard Biological Parts, formed by MIT, to lyse Escherichia coli (E. coli). The lysis gene is regulated by a synthetic genetic lysis circuit, using an inducer-regulated promoter-RBS component. To make the design more easily, it is necessary to provide a systematic approach for a genetic lysis circuit to achieve control of cell population density.

RESULTS

Firstly, the lytic ability of the constructed genetic lysis circuit is described by the relationship between the promoter-RBS components and inducer concentration in a steady state model. Then, three types of promoter-RBS libraries are established. Finally, according to design specifications, a systematic design approach is proposed to provide synthetic biologists with a prescribed I/O response by selecting proper promoter-RBS component set in combination with suitable inducer concentrations, within a feasible range.

CONCLUSION

This study provides an important systematic design method for the development of next-generation synthetic gene circuits, from component library construction to genetic circuit assembly. In future, when libraries are more complete, more precise cell density control can be achieved.

摘要

背景

细胞群体控制有助于维持特定的细胞群体密度。在本研究中,我们使用由麻省理工学院构建的标准生物部件登记册中的裂解基因BBa_K117000来裂解大肠杆菌(E. coli)。该裂解基因由一个合成遗传裂解电路调控,该电路使用诱导物调控的启动子 - 核糖体结合位点(RBS)组件。为了使设计更简便,有必要为遗传裂解电路提供一种系统方法,以实现对细胞群体密度的控制。

结果

首先,在稳态模型中通过启动子 - RBS组件与诱导物浓度之间的关系描述了构建的遗传裂解电路的裂解能力。然后,建立了三种类型的启动子 - RBS文库。最后,根据设计规范,提出了一种系统设计方法,通过在可行范围内选择合适的启动子 - RBS组件集并结合适当的诱导物浓度,为合成生物学家提供规定的输入/输出响应。

结论

本研究为下一代合成基因电路的开发提供了一种重要的系统设计方法,从组件文库构建到遗传电路组装。未来,当文库更完善时,可以实现更精确的细胞密度控制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9fb/4305986/2186a41d99c5/1752-0509-8-S5-S7-1.jpg

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