【2h】

Noise-based switches and amplifiers for gene expression

机译:用于基因表达的基于噪声的开关和放大器

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摘要

The regulation of cellular function is often controlled at the level of gene transcription. Such genetic regulation usually consists of interacting networks, whereby gene products from a single network can act to control their own expression or the production of protein in another network. Engineered control of cellular function through the design and manipulation of such networks lies within the constraints of current technology. Here we develop a model describing the regulation of gene expression and elucidate the effects of noise on the formulation. We consider a single network derived from bacteriophage λ and construct a two-parameter deterministic model describing the temporal evolution of the concentration of λ repressor protein. Bistability in the steady-state protein concentration arises naturally, and we show how the bistable regime is enhanced with the addition of the first operator site in the promotor region. We then show how additive and multiplicative external noise can be used to regulate expression. In the additive case, we demonstrate the utility of such control through the construction of a protein switch, whereby protein production is turned “on” and “off” by using short noise pulses. In the multiplicative case, we show that small deviations in the transcription rate can lead to large fluctuations in the production of protein, and we describe how these fluctuations can be used to amplify protein production significantly. These results suggest that an external noise source could be used as a switch and/or amplifier for gene expression. Such a development could have important implications for gene therapy.
机译:细胞功能的调节通常在基因转录水平上进行控制。这种遗传调节通常由相互作用的网络组成,来自单个网络的基因产物可以用来控制自己在另一个网络中的表达或蛋白质的生产。通过此类网络的设计和操纵对蜂窝功能进行工程控制,属于当前技术的限制。在这里,我们开发了一个描述基因表达调控的模型,并阐明了噪声对制剂的影响。我们考虑一个从噬菌体λ衍生的单一网络,并构建一个描述λ阻遏蛋白浓度随时间变化的两参数确定性模型。稳态蛋白质浓度中的双稳态自然而然地出现,我们展示了如何通过在启动子区域添加第一个操作位点来增强双稳态机制。然后,我们说明如何使用加性和乘性外部噪声来调节表达。在加性情况下,我们通过构建蛋白质开关展示了这种控制的实用性,通过使用短噪声脉冲,蛋白质生产被“打开”和“关闭”。在相乘的情况下,我们表明转录速率的小偏差会导致蛋白质产量的大幅波动,并描述了如何利用这些波动来显着放大蛋白质产量。这些结果表明,外部噪声源可以用作基因表达的开关和/或放大器。这种发展可能会对基因治疗产生重要影响。

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