In-Silico Analysis and Implementation of a Multicellular Feedback Control Strategy in a Synthetic Bacterial Consortium

Gianfranco Fiore, Antoni Matyjaszkiewicz, Fabio Annunziata, Claire Grierson, Nigel Savery, Lucia Marucci, Mario Di Bernardo

Research output: Contribution to journalArticle (Academic Journal)

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Abstract

Living organisms employ endogenous negative feedback loops to maintain homeostasis despite environmental fluctuations. A pressing open challenge in Synthetic Biology is to design and implement synthetic circuits to control host cells' behavior, in order to regulate and maintain desired conditions. To cope with the high degree of circuit complexity required to accomplish this task and the intrinsic modularity of classical control schemes, we suggest the implementation of synthetic endogenous feedback loops across more than one cell population. The distribution of the sensing, computation and actuation functions required to achieve regulation across different cell populations within a consortium allows the genetic engineering in a particular cell to be reduced, increases the robustness, and makes it possible to reuse the synthesized modules for different control applications. Here, we analyze, in-silico, the design of a synthetic feedback controller implemented across two cell populations in a consortium. We study the effects of distributing the various functions required to build a control system across two populations, prove the robustness and modularity of the strategy described and provide a computational proof-of-concept of its feasibility.
Original languageEnglish
Pages (from-to)507–517
Number of pages11
JournalACS Synthetic Biology
Volume6
Issue number3
Early online date20 Dec 2016
DOIs
Publication statusPublished - 17 Mar 2017

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Structured keywords

  • Bristol BioDesign Institute
  • BrisSynBio

Keywords

  • E. coli
  • feedback control
  • gene networks
  • mathematical modeling
  • synthetic biology
  • synthetic microbial consortia

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