序列逻辑和遗传电路的算法编程,用于记录益生菌细菌中的生物化学度
Matthew Lebovich1,2, Min Zeng1, Lauren B Andrews1,2,3
1Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.
ACS synthetic biology
|August 15, 2023
概括
具有遗传记忆电路的工程益生菌可以诊断肠道疾病. 本研究提出了一个计算方法来设计这些电路在益生菌大肠杆菌尼斯尔1917 (EcN) 准确的信号记录.
科学领域:
- 合成生物学 合成生物学
- 微生物工程 微生物工程
- 遗传电路设计的设计
背景情况:
- 工程益生菌通过报告检测到的生物标志物提供非侵入性胃肠道诊断.
- 遗传电路需要记忆功能来记录益生菌微生物中的信号.
- 了解临床相关菌株的电路组件性能,如埃舍里希亚大肠杆菌尼斯尔1917 (EcN) 是至关重要的.
研究的目的:
- 开发一种可扩展的计算方法,用于在Escherichia coli Nissle 1917 (EcN) 中设计强大的序列逻辑电路.
- 为了使工程益生菌能够记录和报告胃肠道内检测到的信号.
- 为肠道环境创建多重诊断工具.
主要方法:
- 利用TetR家族的转录抑制剂来构建序列逻辑电路的遗传逻辑门.
- 在实验中,在EcN中特征了16个遗传 NOT 门和9个传感器.
- 为遗传电路采用基于理论的,可扩展的计算设计方法.
主要成果:
- 在EcN中成功设计和预测了序列逻辑电路的性能.
- 证明了编码组合逻辑和顺序逻辑的遗传电路,其输出与预测相匹配.
- 开发了一种类似模拟的度记录电路,可以检测三种输入信号范围.
结论:
- 开发的计算方法使得在益生菌菌株EcN.中能够设计出强大的序列逻辑电路.
- 这项工作推动了工程益生菌作为具有遗传编码记忆的诊断工具的使用.
- 这些发现支持多重生物标志物查询和在肠道中记录模拟信号.
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