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Contextual dependencies expand the re-usability of genetic inverters

Lookup NU author(s): Dr Lewis Grozinger, Ruud Stoof, Dr Angel Goni-Moreno

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2021, The Author(s).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.


Publication metadata

Author(s): Tas H, Grozinger L, Stoof R, de Lorenzo V, Goni-Moreno A

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2021

Volume: 12

Issue: 1

Online publication date: 13/01/2021

Acceptance date: 02/12/2020

Date deposited: 25/08/2023

ISSN (electronic): 2041-1723

Publisher: Nature Research

URL: https://doi.org/10.1038/s41467-020-20656-5

DOI: 10.1038/s41467-020-20656-5


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Funding

Funder referenceFunder name
2019-T1/BIO-14053
BioRoboost
Agencia Estatal de Investigación
Comunidad de Madrid
Engineering and Physical Sciences Research Council
EP/R019002/1EPSRC
European Structural and Investment Funds
European Union
H2020-NMBP-BIO-CSA-2018/ 820699
InGEMICS-CM
FSE, FECER
MINECO/FEDER
H2020-FET-OPEN-RIA-2017-1-766975
H2020-Grant 870294
H2020-NMBP/0500
MADONNA
MIX-UP
PCI2019-111859-2 ERA-COBIOTECH 2018
S2017/BMD-3691
Severo Ochoa Program for Centres of Excellence in R&D
SYCOLIM
SynBio3D
SYNBIO4FLAV
RTI2018-095584-B-C42
SETH
SEV-2016-0672
Spanish Ministry of Science and Innovation

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