A Framework for Engineering Stress Resilient Plants Using Genetic Feedback Control and Regulatory Network Rewiring

Mathias Foo, Iulia Gherman, Peijun Zhang, Declan Bates, Katherine Denby

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    11 Citations (Scopus)
    216 Downloads (Pure)

    Abstract

    Crop disease leads to significant waste worldwide, both pre- and postharvest, with subsequent economic and sustainability consequences. Disease outcome is determined both by the plants’ response to the pathogen and by the ability of the pathogen to suppress defense responses and manipulate the plant to enhance colonization. The defense response of a plant is characterized by significant transcriptional reprogramming mediated by underlying gene regulatory networks, and components of these networks are often targeted by attacking pathogens. Here, using gene expression data from Botrytis cinerea-infected Arabidopsis plants, we develop a systematic approach for mitigating the effects of pathogen-induced network perturbations, using the tools of synthetic biology. We employ network inference and system identification techniques to build an accurate model of an Arabidopsis defense subnetwork that contains key genes determining susceptibility of the plant to the pathogen attack. Once validated against time-series data, we use this model to design and test perturbation mitigation strategies based on the use of genetic feedback control. We show how a synthetic feedback controller can be designed to attenuate the effect of external perturbations on the transcription factor CHE in our subnetwork. We investigate and compare two approaches for implementing such a controller biologically—direct implementation of the genetic feedback controller, and rewiring the regulatory regions of multiple genes—to achieve the network motif required to implement the controller. Our results highlight the potential of combining feedback control theory with synthetic biology for engineering plants with enhanced resilience to environmental stress.
    Original languageEnglish
    Article number7
    Pages (from-to)1553-1564
    Number of pages12
    JournalACS Synthetic Biology
    Volume7
    Issue number6
    Early online date10 May 2018
    DOIs
    Publication statusPublished - 15 Jun 2018

    Bibliographical note

    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://dx.doi.org/10.1021/acssynbio.8b00037

    Keywords

    • feedback control
    • synthetic gene circuits
    • plant−pathogen interaction
    • plant synthetic biology
    • plant defense response
    • network rewiring

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