Contextual dependencies expand the re-usability of genetic inverters
The implementation of Boolean logic circuits in cells have become a very active field within synthetic biology. Although these are mostly focussed on the genetic components alone, the context in which the circuit performs is crucial for its outcome. We characterise 20 genetic NOT logic gates in up to 7 bacterial-based contexts each, to generate 135 different functions. The contexts we focus on are combinations of four plasmid backbones and three hosts, two Escherichia coli and one Pseudomonas putida strains. Each gate shows seven different dynamic behaviours, depending on the context. That is, gates can be fine-tuned by changing only contextual parameters, thus improving the compatibility between gates. Finally, we analyse portability by measuring, scoring, and comparing gate performance across contexts. Rather than being a limitation, we argue that the effect of the genetic background on synthetic constructs expands functionality, and advocate for considering context as a fundamental design parameter.
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Nature Publishing Group
2021-01-13
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Subjects: | Bacteria (microorganisms), Escherichia coli, Pseudomonas putida, |
Online Access: | http://hdl.handle.net/10261/283932 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/100012818 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100004837 https://api.elsevier.com/content/abstract/scopus_id/85099408249 |
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Bacteria (microorganisms) Escherichia coli Pseudomonas putida Bacteria (microorganisms) Escherichia coli Pseudomonas putida Tas, Huseyin Grozinger, Lewis Stoof, Ruud de Lorenzo, Victor Goñi-Moreno, Ángel Contextual dependencies expand the re-usability of genetic inverters |
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The implementation of Boolean logic circuits in cells have become a very active field within synthetic biology. Although these are mostly focussed on the genetic components alone, the context in which the circuit performs is crucial for its outcome. We characterise 20 genetic NOT logic gates in up to 7 bacterial-based contexts each, to generate 135 different functions. The contexts we focus on are combinations of four plasmid backbones and three hosts, two Escherichia coli and one Pseudomonas putida strains. Each gate shows seven different dynamic behaviours, depending on the context. That is, gates can be fine-tuned by changing only contextual parameters, thus improving the compatibility between gates. Finally, we analyse portability by measuring, scoring, and comparing gate performance across contexts. Rather than being a limitation, we argue that the effect of the genetic background on synthetic constructs expands functionality, and advocate for considering context as a fundamental design parameter. |
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Ministerio de Economía y Competitividad (España) |
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Ministerio de Economía y Competitividad (España) Tas, Huseyin Grozinger, Lewis Stoof, Ruud de Lorenzo, Victor Goñi-Moreno, Ángel |
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Bacteria (microorganisms) Escherichia coli Pseudomonas putida |
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Tas, Huseyin Grozinger, Lewis Stoof, Ruud de Lorenzo, Victor Goñi-Moreno, Ángel |
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Tas, Huseyin |
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Contextual dependencies expand the re-usability of genetic inverters |
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Contextual dependencies expand the re-usability of genetic inverters |
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Contextual dependencies expand the re-usability of genetic inverters |
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Contextual dependencies expand the re-usability of genetic inverters |
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Contextual dependencies expand the re-usability of genetic inverters |
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contextual dependencies expand the re-usability of genetic inverters |
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Nature Publishing Group |
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2021-01-13 |
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http://hdl.handle.net/10261/283932 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/100012818 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100004837 https://api.elsevier.com/content/abstract/scopus_id/85099408249 |
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AT tashuseyin contextualdependenciesexpandthereusabilityofgeneticinverters AT grozingerlewis contextualdependenciesexpandthereusabilityofgeneticinverters AT stoofruud contextualdependenciesexpandthereusabilityofgeneticinverters AT delorenzovictor contextualdependenciesexpandthereusabilityofgeneticinverters AT gonimorenoangel contextualdependenciesexpandthereusabilityofgeneticinverters |
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dig-inia-es-10261-2839322023-02-03T21:35:44Z Contextual dependencies expand the re-usability of genetic inverters Tas, Huseyin Grozinger, Lewis Stoof, Ruud de Lorenzo, Victor Goñi-Moreno, Ángel Ministerio de Economía y Competitividad (España) European Commission Ministerio de Ciencia e Innovación (España) Comunidad de Madrid Agencia Estatal de Investigación (España) Tas, Huseyin [0000-0003-4804-2237] Grozinger, Lewis [0000-0002-9024-701X] Stoof, Ruud [0000-0001-9456-9975] de Lorenzo, Victor [0000-0002-6041-2731] Goñi-Moreno, Ángel [0000-0002-2097-2507] Bacteria (microorganisms) Escherichia coli Pseudomonas putida The implementation of Boolean logic circuits in cells have become a very active field within synthetic biology. Although these are mostly focussed on the genetic components alone, the context in which the circuit performs is crucial for its outcome. We characterise 20 genetic NOT logic gates in up to 7 bacterial-based contexts each, to generate 135 different functions. The contexts we focus on are combinations of four plasmid backbones and three hosts, two Escherichia coli and one Pseudomonas putida strains. Each gate shows seven different dynamic behaviours, depending on the context. That is, gates can be fine-tuned by changing only contextual parameters, thus improving the compatibility between gates. Finally, we analyse portability by measuring, scoring, and comparing gate performance across contexts. Rather than being a limitation, we argue that the effect of the genetic background on synthetic constructs expands functionality, and advocate for considering context as a fundamental design parameter. This work was funded by the SETH (RTI2018-095584-B-C42) (MINECO/FEDER), SYCOLIM (PCI2019-111859-2 ERA-COBIOTECH 2018) Project of the Spanish Ministry of Science and Innovation. MADONNA (H2020-FET-OPEN-RIA-2017-1-766975), BioRoboost (H2020-NMBP-BIO-CSA-2018/ 820699), SYNBIO4FLAV (H2020-NMBP/0500) and MIX-UP (H2020-Grant 870294) Contracts of the European Union, the InGEMICS-CM (S2017/BMD-3691) Project of the Comunidad de Madrid - European Structural and Investment Funds - (FSE, FECER), and the SynBio3D project of the UK Engineering and Physical Sciences Research Council (EP/R019002/1). G-M was also supported by grants from Comunidad de Madrid (Atracción de Talento Program, grant 2019-T1/BIO-14053) and the Severo Ochoa Program for Centres of Excellence in R&D from the Agencia Estatal de Investigación of Spain, grant SEV-2016-0672 (2017-2021). Peer reviewed 2022-11-28T11:13:20Z 2022-11-28T11:13:20Z 2021-01-13 artículo Nature Communications 12(1): 355 (2021) 2041-1723 http://hdl.handle.net/10261/283932 10.1038/s41467-020-20656-5 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/100012818 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100004837 33441561 2-s2.0-85099408249 https://api.elsevier.com/content/abstract/scopus_id/85099408249 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095584-B-C42/ES/PROGRAMACION GENETICA DE PSEUDOMONAS PUTIDA PARA UNA EFICACIA CATALITICA SOSTENIDA A TRAVES DE LA ESCALA DE DISPONIBILIDAD DE AGUA/ info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PCI2019-111859-2/ES/COMUNIDADES MICROBIANAS SINTETICAS PARA LA PRODUCCION DE PRODUCTOS DERIVADOS DEL LIMONENO/ info:eu-repo/grantAgreement/EC/H2020/766975 info:eu-repo/grantAgreement/EC/H2020/820699 info:eu-repo/grantAgreement/EC/H2020/870294 S2017/BMD-3691 S2019-T1/BIO-14053 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2021/SEV-2016-0672 Nature communications Publisher's version Sí open Nature Publishing Group |