Computational implementation of a tunable multicellular memory circuit for engineered eukaryotic consortia

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  • dc.contributor.author Sardanyés i Cayuela, Josepca
  • dc.contributor.author Bonforti, Adrianoca
  • dc.contributor.author Conde Pueyo, Núria, 1983-ca
  • dc.contributor.author Solé Vicente, Ricard, 1962-ca
  • dc.contributor.author Macía, Javierca
  • dc.date.accessioned 2016-01-26T14:27:29Z
  • dc.date.available 2016-01-26T14:27:29Z
  • dc.date.issued 2015
  • dc.description.abstract Cells are complex machines capable of processing information by means of an entangled network of molecular interactions. A crucial component of these decision-making systems is the presence of memory and this is also a specially relevant target of engineered synthetic systems. A classic example of memory devices is a 1-bit memory element known as the flip-flop. Such system can be in principle designed using a single-cell implementation, but a direct mapping between standard circuit design and a living circuit can be cumbersome. Here we present a novel computational implementation of a 1-bit memory device using a reliable multicellular design able to behave as a set-reset flip-flop that could be implemented in yeast cells. The dynamics of the proposed synthetic circuit is investigated with a mathematical model using biologically-meaningful parameters. The circuit is shown to behave as a flip-flop in a wide range of parameter values. The repression strength for the NOT logics is shown to be crucial to obtain a good flip-flop signal. Our model also shows that the circuit can be externally tuned to achieve different memory states and dynamics, such as persistent and transient memory. We have characterized the parameter domains for robust memory storage and retrieval as well as the corresponding time response dynamics.ca
  • dc.description.sponsorship This work was partially funded by the European Research Council Grant ERC SYNCOM 294294 (JM, RS, AB, NC), by grants of the Botin Foundation, by Banco Santander through its Santander Universities Global Division (RS, JS), and the Santa Fe Institute (RS).
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Sardanyés J, Bonforti A, Conde N, Solé R, Macia J. Computational implementation of a tunable multicellular memory circuit for engineered eukaryotic consortia. Frontiers in physiology. 2015; 6: 281. DOI 10.3389/fphys.2015.00281ca
  • dc.identifier.doi http://dx.doi.org/10.3389/fphys.2015.00281
  • dc.identifier.issn 1664-042X
  • dc.identifier.uri http://hdl.handle.net/10230/25661
  • dc.language.iso engca
  • dc.publisher Frontiersca
  • dc.relation.ispartof Frontiers in physiology. 2015;6:281
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/294294
  • dc.rights © 2015 Sardanyés, Bonforti, Conde, Solé and Macia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Computational modeling
  • dc.subject.keyword Eukaryotic memory circuits
  • dc.subject.keyword Flip-flop
  • dc.subject.keyword Multicellular circuits
  • dc.subject.keyword Synthetic biology
  • dc.subject.other Molècules -- Modelsca
  • dc.title Computational implementation of a tunable multicellular memory circuit for engineered eukaryotic consortiaca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca