Titre
Mechanistic Modeling of Genetic Circuits for ArsR Arsenic Regulation.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Berset, Y.
Auteure/Auteur
Merulla, D.
Auteure/Auteur
Joublin, A.
Auteure/Auteur
Hatzimanikatis, V.
Auteure/Auteur
van der Meer, J.R.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2161-5063
Statut éditorial
Publié
Date de publication
2017-05-19
Volume
6
Numéro
5
Première page
862
Dernière page/numéro d’article
874
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Bioreporters are living cells that generate an easily measurable signal in the presence of a chemical compound. They acquire their functionality from synthetic gene circuits, the configuration of which defines the response signal and signal-to-noise ratio. Bioreporters based on the Escherichia coli ArsR system have raised significant interest for quantifying arsenic pollution, but they need to be carefully optimized to accurately work in the required low concentration range (1-10 μg arsenite L-1). To better understand the general functioning of ArsR-based genetic circuits, we developed a comprehensive mechanistic model that was empirically tested and validated in E. coli carrying different circuit configurations. The model accounts for the different elements in the circuits (proteins, DNA, chemical species), and their detailed affinities and interactions, and predicts the (fluorescent) output from the bioreporter cell as a function of arsenite concentration. The model was parametrized using existing ArsR biochemical data, and then complemented by parameter estimations from the accompanying experimental data using a scatter search algorithm. Model predictions and experimental data were largely coherent for feedback and uncoupled circuit configurations, different ArsR alleles, promoter strengths, and presence or absence of arsenic efflux in the bioreporters. Interestingly, the model predicted a particular useful circuit variant having steeper response at low arsenite concentrations, which was experimentally confirmed and may be useful as arsenic bioreporter in the field. From the extensive validation we expect the mechanistic model to further be a useful framework for detailed modeling of other synthetic circuits.
PID Serval
serval:BIB_7DB8AF3E6328
PMID
Date de création
2017-02-28T18:12:33.823Z
Date de création dans IRIS
2025-05-21T02:36:13Z