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A simple model for Lutz and Bujard's controllable promoters and its application for analyzing a simple genetic oscillator

机译:Lutz 和 Bujard 可控启动子的简单模型及其在分析简单遗传振荡器中的应用

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摘要

We develop an exact and flexible mathematical model for Lutz and Bujard's controllable promoters. It can be used as a building block for modeling genetic systems based on them. Special attention is paid to deduce all the model parameters from reported (in vitro) experimental data. We validate our model by comparing the regulatory ranges measured in vivo by Lutz and Bujard against the ranges predicted by the model, and which are calculated as the reporter activity obtained under inducing conditions divided by the activity measured under maximal repression. In particular, we verify Bond et al. assertion that the cooperativity between two lac operators can be assumed to be negligible when their central base pairs are separated by 22 or 32 bp Gene repression by minimal lac loops in vivo, Nucleic Acids Res, 38 (2010) 8072-8082. Moreover, we also find that the probability that two repressors Lacl bind to these operators at the same time can be assumed to be negligible as well. We finally use the model for the promoter P_(LlacO-1) to analyze a synthetic genetic oscillator recently build by Stricker et al. A fast, robust and tunable synthetic gene oscillator, Nature, 456 (2008) 516-519.
机译:我们为 Lutz 和 Bujard 的可控启动子开发了一个精确而灵活的数学模型。它可以用作基于它们的遗传系统建模的构建块。特别注意从报告的(体外)实验数据中推断出所有模型参数。我们通过将 Lutz 和 Bujard 在体内测量的调节范围与模型预测的范围进行比较来验证我们的模型,这些范围的计算方法是在诱导条件下获得的报告基因活性除以在最大抑制下测量的活性。特别是,我们验证了 Bond 等人的断言,即当两个 lac 操作者的中心碱基对相隔 22 或 32 bp 时,可以假设它们之间的合作性可以忽略不计 [Gene repression by minimal lac loops in vivo, Nucleic Acids Res, 38 (2010) 8072-8082]。此外,我们还发现,两个阻遏因子Lacl同时与这些算子结合的概率也可以忽略不计。最后,我们使用启动子P_(LlacO-1)的模型来分析Stricker等人最近构建的合成遗传振荡器[一种快速,稳健和可调的合成基因振荡器,Nature,456(2008)516-519]。

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