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A Multilayer Microfluidic Platform for the Conduction of Prolonged Cell-Free Gene Expression
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An integrative circuit-host modelling framework for predicting synthetic gene network behaviours.

Chen Liao1,2, Andrew E Blanchard2,3, Ting Lu4,5,6,7

  • 1Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.

Nature Microbiology
|September 27, 2017
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Summary

This study presents a new gene circuit modeling framework that links synthetic biology circuits with host physiology. This bidirectional coupling improves prediction of engineered gene circuit behaviors in synthetic biology.

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Area of Science:

  • Synthetic biology
  • Systems biology
  • Computational biology

Background:

  • Quantitative prediction of engineered gene circuit behavior is a major challenge in synthetic biology.
  • The complex interdependence between gene circuits and their host organisms contributes to this challenge.

Purpose of the Study:

  • To develop a modeling framework that integrates gene circuit behavior with host physiology.
  • To enable accurate prediction and understanding of engineered gene circuit dynamics.

Main Methods:

  • A mechanistic, coarse-grained host physiology model with dynamic resource partitioning.
  • Multilayered, bidirectional coupling between circuits and host, including generic and specific interactions.
  • A detailed kinetic module for exogenous circuits.

Main Results:

  • The framework successfully captured and predicted experimental data for host and foreign gene overexpression.
  • Analysis of a growth-modulating feedback circuit revealed altered dynamics due to circuit-host interactions.
  • An extended framework elucidated toggle switch behaviors across single-cell, population, and spatial scales.

Conclusions:

  • The developed framework advances quantitative understanding of gene circuit behaviors.
  • This approach benefits the rational design of synthetic gene networks by accounting for circuit-host interactions.