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Model-Driven Designs of an Oscillating Gene Network

机译:振荡基因网络的模型驱动设计

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摘要

The current rapid expansion of biological knowledge offers a great opportunity to rationally engineer biological systems that respond to signals such as light and chemical inducers by producing specific proteins. Turning on and off the production of proteins on demand holds great promise for creating significant biotechnological and biomedical applications. With successful stories already registered, the challenge still lies with rationally engineering gene regulatory networks which, like electronic circuits, sense inputs and generate desired outputs. From the literature, we have found kinetic and thermodynamic information describing the molecular components and interactions of the transcriptionally repressing lac, tet, and ara operons. Connecting these components in a model gene network, we determine how to change the kinetic parameters to make this normally nonperiodic system one which has well-defined oscillations. Simulating the designed lac-tet-ara gene network using a hybrid stochastic-discrete and stochastic-continuous algorithm, we seek to elucidate the relationship between the strength and type of specific connections in the gene network and the oscillatory nature of the protein product. Modeling the molecular components of the gene network allows the simulation to capture the dynamics of the real biological system. Analyzing the effect of modifications at this level provides the ability to predict how changes to experimental systems will alter the network behavior, while saving the time and expense of trial and error experimental modifications.
机译:当前生物学知识的迅速扩展为合理地设计生物系统提供了巨大的机会,这些生物系统通过产生特定的蛋白质来响应诸如光和化学诱导剂等信号。开启和关闭按需蛋白质的生产对于创建重要的生物技术和生物医学应用具有广阔的前景。有了成功的故事,挑战仍然在于合理设计基因调控网络,像电子电路一样,感应输入并产生所需的输出。从文献中,我们发现了动力学和热力学信息,这些信息描述了转录抑制lac,tet和ara操纵子的分子成分和相互作用。将这些组件连接到模型基因网络中,我们确定如何更改动力学参数,以使此通常为非周期性的系统具有明确的振荡。我们使用混合随机离散和随机连续算法模拟设计的lac-tet-ara基因网络,我们试图阐明基因网络中特定连接的强度和类型与蛋白质产物的振荡性质之间的关系。对基因网络的分子成分进行建模可以使仿真捕获真实生物系统的动态。在此级别上分析修改的效果,可以预测对实验系统的更改将如何改变网络行为,同时节省了尝试和错误实验修改的时间和费用。

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