Tica Jure, Zhu Tong, Isalan Mark
Department of Life Sciences Imperial College London London SW7 2AZ UK.
Eng Biol. 2020 Jun 23;4(2):25-31. doi: 10.1049/enb.2020.0009. eCollection 2020 Jun.
Applying the principles of engineering to Synthetic Biology relies on the development of robust and modular genetic components, as well as underlying quantitative dynamical models that closely predict their behaviour. This study looks at a simple positive feedback circuit built by placing filamentous phage secretin pIV under a phage shock promoter. A single-equation ordinary differential equation model is developed to closely replicate the behaviour of the circuit, and its response to inhibition by TetR. A stepwise approach is employed to fit the model's parameters to time-series data for the circuit. This approach allows the dissection of the role of different parameters and leads to the identification of dependencies and redundancies between parameters. The developed genetic circuit and associated model may be used as a building block for larger circuits with more complex dynamics, which require tight quantitative control or tuning.
将工程原理应用于合成生物学依赖于强大且模块化的遗传元件的开发,以及能够精确预测其行为的基础定量动力学模型。本研究着眼于通过将丝状噬菌体分泌蛋白pIV置于噬菌体休克启动子之下构建的一个简单正反馈回路。开发了一个单方程常微分方程模型来紧密复制该回路的行为及其对TetR抑制的响应。采用逐步方法将模型参数与该回路的时间序列数据进行拟合。这种方法能够剖析不同参数的作用,并有助于识别参数之间的依赖性和冗余性。所开发的遗传回路及相关模型可作为具有更复杂动力学的更大回路的构建模块,这些更大的回路需要严格的定量控制或调节。