Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia
Engineered synthetic biological devices have been designed to perform a variety of functions from sensing molecules and bioremediation to energy production and biomedicine. Notwithstanding, a major limitation of in vivo circuit implementation is the constraint associated to the use of standard methodologies for circuit design. Thus, future success of these devices depends on obtaining circuits with scalable complexity and reusable parts. Here we show how to build complex computational devices using multicellular consortia and space as key computational elements. This spatial modular design grants scalability since its general architecture is independent of the circuit’s complexity, minimizes wiring requirements and allows component reusability with minimal genetic engineering. The potential use of this approach is demonstrated by implementation of complex logical functions with up to six inputs, thus demonstrating the scalability and flexibility of this method. The potential implications of our results are outlined.
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2016-02-01
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Engineered synthetic biological devices have been designed to perform a variety of functions from sensing molecules and bioremediation to energy production and biomedicine. Notwithstanding, a major limitation of in vivo circuit implementation is the constraint associated to the use of standard methodologies for circuit design. Thus, future success of these devices depends on obtaining circuits with scalable complexity and reusable parts. Here we show how to build complex computational devices using multicellular consortia and space as key computational elements. This spatial modular design grants scalability since its general architecture is independent of the circuit’s complexity, minimizes wiring requirements and allows component reusability with minimal genetic engineering. The potential use of this approach is demonstrated by implementation of complex logical functions with up to six inputs, thus demonstrating the scalability and flexibility of this method. The potential implications of our results are outlined. |
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European Commission Macía, Javier Manzoni, Romilde Conde-Pueyo, Núria Urrios, Arturo Nadal, Eulàlia de Solé, Ricard V. Posas, Francesc |
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Macía, Javier Manzoni, Romilde Conde-Pueyo, Núria Urrios, Arturo Nadal, Eulàlia de Solé, Ricard V. Posas, Francesc |
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Macía, Javier Manzoni, Romilde Conde-Pueyo, Núria Urrios, Arturo Nadal, Eulàlia de Solé, Ricard V. Posas, Francesc Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia |
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Macía, Javier |
title |
Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia |
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Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia |
title_full |
Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia |
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Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia |
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Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia |
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implementation of complex biological logic circuits using spatially distributed multicellular consortia |
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Public Library of Science |
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2016-02-01 |
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http://hdl.handle.net/10261/151818 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100000781 http://dx.doi.org/10.13039/501100006373 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100002809 http://dx.doi.org/10.13039/501100003043 http://dx.doi.org/10.13039/501100003741 http://dx.doi.org/10.13039/100010784 http://dx.doi.org/10.13039/100011419 |
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dig-ibe-es-10261-1518182021-12-28T16:20:39Z Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia Macía, Javier Manzoni, Romilde Conde-Pueyo, Núria Urrios, Arturo Nadal, Eulàlia de Solé, Ricard V. Posas, Francesc European Commission European Research Council Santa Fe Institute (US) Fundación Botín Banco Santander Ministerio de Economía y Competitividad (España) Generalitat de Catalunya Fundación "la Caixa" EMBO Institución Catalana de Investigación y Estudios Avanzados Engineered synthetic biological devices have been designed to perform a variety of functions from sensing molecules and bioremediation to energy production and biomedicine. Notwithstanding, a major limitation of in vivo circuit implementation is the constraint associated to the use of standard methodologies for circuit design. Thus, future success of these devices depends on obtaining circuits with scalable complexity and reusable parts. Here we show how to build complex computational devices using multicellular consortia and space as key computational elements. This spatial modular design grants scalability since its general architecture is independent of the circuit’s complexity, minimizes wiring requirements and allows component reusability with minimal genetic engineering. The potential use of this approach is demonstrated by implementation of complex logical functions with up to six inputs, thus demonstrating the scalability and flexibility of this method. The potential implications of our results are outlined. [Author Summary] Synthetic biological circuits have been built for different purposes. Nevertheless, the way these devices have been designed so far present several limitations: complex genetic engineering is required to implement complex circuits, and once the parts are built, they are not reusable. We proposed to distribute the computation in several cellular consortia that are physically separated, thus ensuring implementation of circuits independently of their complexity and using reusable components with minimal genetic engineering. This approach allows an easy implementation of multicellular computing devices for secretable inputs or biosensing purposes. This work was supported by an ERC Advanced Grant Number 294294 from the EU seventh framework program (SYNCOM) to RS and FP, and the Santa Fe Institute to RS. FP and RS laboratories are also supported by Fundación Botín, by Banco Santander through its Santander Universities Global Division. The laboratory of FP and EdN is supported by grants from the Spanish Government (BFU2012-33503/ BFU2015-64437 P and FEDER to FP; BFU2014-52333-P and FEDER to EdN) and the Catalan Government (2014 SGR 599). The research leading to these results has received funding from “la Caixa” Foundation in collaboration with “Centre per a la Innovació de la Diabetis Infantil Sant Joan de Déu (CIDI)”. FP and EdN are recipients of an ICREA Acadèmia (Generalitat de Catalunya). RM was a former EMBO postdoctoral fellow. AU is a recipient of a “La Caixa” fellowship. Peer reviewed 2017-06-22T08:48:34Z 2017-06-22T08:48:34Z 2016-02-01 artículo http://purl.org/coar/resource_type/c_6501 PLoS Computational Biology 12(2): e1004685 (2016) 1553-734X http://hdl.handle.net/10261/151818 10.1371/journal.pcbi.1004685 1553-7358 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100000781 http://dx.doi.org/10.13039/501100006373 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100002809 http://dx.doi.org/10.13039/501100003043 http://dx.doi.org/10.13039/501100003741 http://dx.doi.org/10.13039/100010784 http://dx.doi.org/10.13039/100011419 26829588 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/EC/FP7/294294 info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2015-64437-P info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2014-52333-P Publisher's version https://doi.org/10.1371/journal.pcbi.1004685 Sí open Public Library of Science |