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Dynamical model fitting to a synthetic positive feedback circuit in E. coli
Jure Tica1, Tong Zhu1, Mark Isalan1
1Department of Life Sciences Imperial College London London SW7 2AZ UK.
Engineering Biology
|March 27, 2023
Summary
This study presents a synthetic biology genetic circuit and a mathematical model to predict its behavior. The model aids in understanding and controlling complex biological systems for engineering applications.
Area of Science:
- Synthetic Biology
- Genetic Engineering
- Systems Biology
Background:
- Engineering principles applied to synthetic biology require robust genetic components and predictive quantitative models.
- Filamentous phage secretin pIV and phage shock promoter are utilized to construct a positive feedback genetic circuit.
Purpose of the Study:
- To develop a quantitative dynamical model for a synthetic genetic circuit.
- To analyze the circuit's behavior and response to inhibition using a stepwise parameter fitting approach.
Main Methods:
- Construction of a positive feedback genetic circuit using filamentous phage secretin pIV and a phage shock promoter.
- Development of a single-equation ordinary differential equation model to simulate circuit behavior.
- Stepwise parameter fitting of the model to time-series data, including response to TetR inhibition.
Main Results:
- A quantitative model accurately replicates the behavior of the engineered genetic circuit.
- Parameter fitting identified dependencies and redundancies, aiding in understanding model behavior.
- The model successfully predicts the circuit's response to inhibition.
Conclusions:
- The developed genetic circuit and its associated mathematical model serve as a foundational building block for more complex synthetic biology systems.
- This work facilitates tight quantitative control and tuning of synthetic biological circuits.
- The methodology enables dissection of parameter roles in biological circuit dynamics.
Keywords:
E. colibiology computingcircuit feedbackcomplex dynamicsdifferential equationsdynamical model fittingfeedbackgeneticsmodular genetic componentsordinary differential equation modelphage shock promoterpositive feedback circuitsynthetic biologysynthetic positive feedback circuittime seriestime‐series data
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