An engineered mammalian band-pass network.
An engineered mammalian band-pass network.
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DOI：
10.1093/nar/gkq671
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发表时间：
2010-10
影响因子：
14.9
通讯作者：
Fussenegger M
中科院分区：
文献类型：
--
作者：
Greber D;Fussenegger M
基因表达电路使细胞能够检测形态发生素浓度梯度内的精确水平，对胚胎模式形成、旁分泌和自分泌信号传导以及细胞迁移等生物过程具有关键影响。我们提出了具有带通检测特性的合成遗传电路的合理合成。这些组件涉及多重连接的哺乳动物反式激活子和反式阻遏物控制系统，经过选择和微调，能够检测“低阈值”形态发生素（四环素）浓度（触发靶基因表达）和“高阈值”浓度（表达减弱）。计算机预测和支持实验结果表明，功能性带通检测的关键标准是能够充分分离低阈值点和高阈值点的组件匹配。使用该电路和荧光编码的靶基因，哺乳动物细胞经过基因工程改造，能够响应四环素化学梯度而形成带状分化模式。旨在模拟自然发生的基因行为的合成基因网络不仅可以深入了解生物过程，还可以促进未来组织工程、基因治疗和生物传感应用的进展。
Gene expression circuitries, which enable cells to detect precise levels within a morphogen concentration gradient, have a pivotal impact on biological processes such as embryonic pattern formation, paracrine and autocrine signalling, and cellular migration. We present the rational synthesis of a synthetic genetic circuit exhibiting band-pass detection characteristics. The components, involving multiply linked mammalian trans-activator and -repressor control systems, were selected and fine-tuned to enable the detection of ‘low-threshold’ morphogen (tetracycline) concentrations, in which target gene expression was triggered, and a ‘high-threshold’ concentration, in which expression was muted. In silico predictions and supporting experimental findings indicated that the key criterion for functional band-pass detection was the matching of componentry that enabled sufficient separation of the low and high threshold points. Using the circuitry together with a fluorescence-encoded target gene, mammalian cells were genetically engineered to be capable of forming a band-like pattern of differentiation in response to a tetracycline chemical gradient. Synthetic gene networks designed to emulate naturally occurring gene behaviours provide not only insight into biological processes, but may also foster progress in future tissue engineering, gene therapy and biosensing applications.
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DOI：
10.1073/pnas.0500345102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Kramer, BP;Fussenegger, M
通讯作者：
Fussenegger, M
影响因子：
64.8
作者：
Becskei, A;Serrano, L
通讯作者：
Serrano, L
影响因子：
46.9
作者：
Fussenegger, M;Morris, RP;Bailey, JE
通讯作者：
Bailey, JE
影响因子：
46.9
作者：
Kramer, BP;Viretta, AU;Fussenegger, M
通讯作者：
Fussenegger, M
影响因子：
3.8
作者：
Karig, D;Weiss, R
通讯作者：
Weiss, R