Resource Competition Shapes the Response of Genetic Circuits

Qian, Y, Huang, H-H, Jimenez, Jose and Del Vecchio, D (2017) Resource Competition Shapes the Response of Genetic Circuits ACS Synthetic Biology, 6 (7). pp. 1263-1272.

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Abstract

A common approach to design genetic circuits is to compose gene expression cassettes together. While appealing, this modular approach is challenged by the fact that expression of each gene depends on the availability of transcriptional/translational resources, which is in turn determined by the presence of other genes in the circuit. This raises the question of how competition for resources by different genes affects a circuit’s behavior. Here, we create a library of genetic activation cascades in E. coli bacteria, where we explicitly tune the resource demand by each gene. We develop a general Hill-function-based model that incorporates resource competition effects through resource demand coefficients. These coefficients lead to non-regulatory interactions among genes that reshape circuit’s behavior. For the activation cascade, such interactions result in surprising biphasic or monotonically decreasing responses. Finally, we use resource demand coefficients to guide the choice of ribosome binding site (RBS) and DNA copy number to restore the cascade’s intended monotonically increasing response. Our results demonstrate how unintended circuit’s behavior arises from resource competition and provide a model-guided methodology to minimize the resulting effects.

Item Type:	Article
Subjects :	Biosciences and Medicine
Divisions :	Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :	Name Email ORCID Qian, Y Huang, H-H Jimenez, Jose j.jimenez@surrey.ac.uk Del Vecchio, D
Date :	28 March 2017
DOI :	10.1021/acssynbio.6b00361
Copyright Disclaimer :	Copyright 2017 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Synthetic Biology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/page/asbcd6/about.html
Uncontrolled Keywords :	genetic circuit, context dependence, modularity, resource competition, modelguided design, activation cascade
Related URLs :	Publisher
Depositing User :	Symplectic Elements
Date Deposited :	26 Apr 2017 09:25
Last Modified :	16 Jan 2019 17:14
URI:	http://epubs.surrey.ac.uk/id/eprint/814030

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