A modular cell-based biosensor using engineered genetic logic circuits to detect and integrate multiple environmental signals.
A modular cell-based biosensor using engineered genetic logic circuits to detect and integrate multiple environmental signals.
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DOI：
10.1016/j.bios.2012.08.011
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发表时间：
2013-02-15
影响因子：
12.6
通讯作者：
Buck, Martin
中科院分区：
文献类型：
--
作者：
Wang, Baojun;Barahona, Mauricio;Buck, Martin
细胞感知各种各样的细胞和环境信号，这些信号通常被组合处理以产生特定的表型反应。在这里，我们采用单一和混合细胞类型群体，通过工程模块化细胞信号和传感电路进行预编程，作为处理单元来检测和整合多个环境信号。基于工程模块化遗传与逻辑门，我们报告了一组可扩展的基于合成微生物的生物传感器的构建，其中包括可交换的传感、信号处理和驱动模块。这些细胞生物传感器使用不同的信号传感模块进行设计，以精确识别各种化学信号及其组合，并具有定量荧光输出。所使用的遗传逻辑门可以充当生物过滤器和放大器，以增强基于细胞的生物传感器的传感选择性和灵敏度。特别是，我们构建了一种基于大肠杆菌联盟的生物传感器，可以通过其天然的双组分信号转导途径或源自其他细菌的合成信号传感器与细胞间通信模块相结合来检测和整合三种环境信号（砷、汞和铜离子水平）。我们展示了如何使用可交换的合成基因电路模块来可预测地设计基于细胞的模块化生物传感器来感测和集成多输入信号。这项研究阐述了这些生物传感器未来在广泛的环境和医疗保健领域的应用所需的一些关键实用设计原则。 ► 模块化细胞生物传感器，包括可交换遗传传感器、逻辑电路和执行器。 ► 一套用于有毒金属和细菌信号分子的生物传感器。 ► 遗传逻辑电路充当生物过滤器和放大器，以增强传感选择性和灵敏度。 ► 使用多个蜂窝联盟的三输入 AND 逻辑门控传感器。
Cells perceive a wide variety of cellular and environmental signals, which are often processed combinatorially to generate particular phenotypic responses. Here, we employ both single and mixed cell type populations, pre-programmed with engineered modular cell signalling and sensing circuits, as processing units to detect and integrate multiple environmental signals. Based on an engineered modular genetic AND logic gate, we report the construction of a set of scalable synthetic microbe-based biosensors comprising exchangeable sensory, signal processing and actuation modules. These cellular biosensors were engineered using distinct signalling sensory modules to precisely identify various chemical signals, and combinations thereof, with a quantitative fluorescent output. The genetic logic gate used can function as a biological filter and an amplifier to enhance the sensing selectivity and sensitivity of cell-based biosensors. In particular, an Escherichia coli consortium-based biosensor has been constructed that can detect and integrate three environmental signals (arsenic, mercury and copper ion levels) via either its native two-component signal transduction pathways or synthetic signalling sensors derived from other bacteria in combination with a cell-cell communication module. We demonstrate how a modular cell-based biosensor can be engineered predictably using exchangeable synthetic gene circuit modules to sense and integrate multiple-input signals. This study illustrates some of the key practical design principles required for the future application of these biosensors in broad environmental and healthcare areas. ► Modular cellular biosensors comprising exchangeable genetic sensors, logic circuits and actuators. ► A set of biosensors for toxic metals and bacterial signalling molecules. ► Genetic logic circuits functioning as biological filters and amplifiers to enhance sensing selectivity and sensitivity. ► A triple-input AND logic gated sensor using multiple cellular consortia.
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DOI：
10.1038/nrm2904
发表时间：
2010-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
9.9
作者：
Saeidi, Nazanin;Wong, Choon Kit;Chang, Matthew Wook
通讯作者：
Chang, Matthew Wook
影响因子：
3.2
作者：
DIORIO, C;CAI, J;DUBOW, MS
通讯作者：
DUBOW, MS
影响因子：
46.9
作者：
Canton, Barry;Labno, Anna;Endy, Drew
通讯作者：
Endy, Drew
影响因子：
16.6
作者：
Jovanovic M;James EH;Burrows PC;Rego FG;Buck M;Schumacher J
通讯作者：
Schumacher J