title: In-Silico Analysis and Implementation of a Multicellular Feedback Control Strategy in a Synthetic Bacterial Consortium.
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.
authors.affiliation: Department of Engineering Mathematics, University of Bristol , Merchant Venturers' Building, Woodland Road, Bristol BS8 1UB, U.K.|BrisSynBio, Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, U.K.
authors.forename: Gianfranco
authors.identifier: 0000-0002-5713-5323
authors.initials: G
authors.lastname: Fiore
authors.affiliation: Department of Engineering Mathematics, University of Bristol , Merchant Venturers' Building, Woodland Road, Bristol BS8 1UB, U.K.|BrisSynBio, Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, U.K.
authors.forename: Antoni
authors.identifier: 0000-0002-8647-5773
authors.initials: A
authors.lastname: Matyjaszkiewicz
authors.affiliation: BrisSynBio, Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, U.K.|School of Biochemistry, University of Bristol , Biomedical Sciences Building, University Walk, Bristol BS8 1TD, U.K.
authors.forename: Fabio
authors.initials: F
authors.lastname: Annunziata
authors.affiliation: BrisSynBio, Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, U.K.|School of Biological Sciences, University of Bristol , Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, U.K.
authors.forename: Claire
authors.initials: C
authors.lastname: Grierson
authors.affiliation: BrisSynBio, Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, U.K.|School of Biochemistry, University of Bristol , Biomedical Sciences Building, University Walk, Bristol BS8 1TD, U.K.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Savery
authors.affiliation: Department of Engineering Mathematics, University of Bristol , Merchant Venturers' Building, Woodland Road, Bristol BS8 1UB, U.K.|BrisSynBio, Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, U.K.
authors.forename: Lucia
authors.initials: L
authors.lastname: Marucci
authors.affiliation: Department of Engineering Mathematics, University of Bristol , Merchant Venturers' Building, Woodland Road, Bristol BS8 1UB, U.K.|BrisSynBio, Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, U.K.|Department of Electrical Engineering and Information Technology, University of Naples Federico II , 80125, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: di Bernardo
mesh_terms: D003198:Computer Simulation; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D005818:Genetic Engineering / Q000379:methods; D006706:Homeostasis / Q000235:genetics; D059013:Microbial Consortia / Q000235:genetics*; D058615:Synthetic Biology / Q000379:methods
keywords: E. coli; feedback control; gene networks; mathematical modeling; synthetic biology; synthetic microbial consortia