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Engineering Translational Resource Allocation Controllers: Mechanistic Models, Design Guidelines, and Potential

Alexander P S Darlington1, Juhyun Kim2, José I Jiménez2

  • 1Warwick Integrative Synthetic Biology Centre, School of Engineering , University of Warwick , Coventry CV4 7AL , U.K.

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|October 23, 2018
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Summary
This summary is machine-generated.

Synthetic biology faces challenges with cellular resource limitations. This study introduces dynamic resource allocation controllers to improve synthetic gene circuit modularity by managing ribosome distribution, offering design guidelines for optimal performance.

Keywords:
feedback controlmodularityorthogonal ribosomesresource competition

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Area of Science:

  • Synthetic Biology
  • Systems Biology
  • Biotechnology

Background:

  • Cellular resource limitations negatively impact synthetic gene circuit modularity.
  • Orthogonal ribosomes offer a potential solution for managing cellular resources.

Purpose of the Study:

  • To develop a mechanistic model for gene expression and resource allocation.
  • To design and analyze dynamic translational resource allocation controllers.
  • To provide design guidelines for optimizing synthetic gene circuits.

Main Methods:

  • Development of a detailed mechanistic model of gene expression and resource allocation.
  • Simplification of the model for rational controller design.
  • Sensitivity analysis of controller parameters.
  • Evaluation of experimental implementations using biological components.

Main Results:

  • Identified a design trade-off where reducing coupling decreases gene expression.
  • Determined how controller parameters influence closed-loop system behavior.
  • Demonstrated the controller's ability to dynamically allocate ribosomes.
  • Showcased restoration of modularity in complex synthetic circuits like repressilators and activation cascades.

Conclusions:

  • Dynamic resource allocation controllers can mitigate cellular resource limitations in synthetic gene circuits.
  • The developed model and guidelines facilitate the rational design of these controllers.
  • The controller effectively restores modularity in complex synthetic circuit architectures.