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

Darlington, Alexander P S, Kim, Juhyun, Jimenez, Jose and Bates, Declan G (2018) Engineering Translational Resource Allocation Controllers: Mechanistic Models, Design Guidelines, and Potential Biological Implementations ACS Synthetic Biology, 7 (11). pp. 2485-2496.

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Abstract

The use of orthogonal ribosomes in combination with dynamic resource allocation controllers is a promising approach for relieving the negative effects of cellular resource limitations on the modularity of synthetic gene circuits. Here, we develop a detailed mechanistic model of gene expression and resource allocation, which when simplified to a tractable level of complexity, allows the rational design of translational resource allocation controllers. Analysis of this model reveals a fundamental design trade-off; that reducing coupling acts to decrease gene expression. Through a sensitivity analysis of the experimentally tuneable controller parameters, we identify how each controller design parameter affects the overall closed-loop behaviour of the system, leading to a detailed set of design guidelines for optimally managing this trade-off. Based on our designs, we evaluated a number of alternative potential experimental implementations of the proposed system using commonly available biological components. Finally, we show that the controller is capable of dynamically allocating ribosomes as needed to restore modularity in a number of more complex synthetic circuits, such as the repressilator, and activation cascades composed of multiple interacting modules.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Darlington, Alexander P S
Kim, Juhyunjuhyun.kim@surrey.ac.uk
Jimenez, Josej.jimenez@surrey.ac.uk
Bates, Declan G
Date : 15 September 2018
DOI : 10.1021/acssynbio.8b00029
Copyright Disclaimer : Copyright © 2018 American Chemical Society
Uncontrolled Keywords : Resource competition; Orthogonal ribosomes; Feedback control; Modularity
Depositing User : Melanie Hughes
Date Deposited : 23 Oct 2018 10:42
Last Modified : 16 Sep 2019 02:08
URI: http://epubs.surrey.ac.uk/id/eprint/849756

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