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Dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design

We introduce a new design framework for implementing negative feedback regulation in synthetic biology, which we term ‘dichotomous feedback’. Our approach is different from current methods, in that it sequesters existing fluxes in the process to be controlled, and in this way takes advantage of the...

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Detalles Bibliográficos
Autores principales: Sootla, Aivar, Delalez, Nicolas, Alexis, Emmanouil, Norman, Arthur, Steel, Harrison, Wadhams, George H., Papachristodoulou, Antonis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019519/
https://www.ncbi.nlm.nih.gov/pubmed/35440202
http://dx.doi.org/10.1098/rsif.2021.0737
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author Sootla, Aivar
Delalez, Nicolas
Alexis, Emmanouil
Norman, Arthur
Steel, Harrison
Wadhams, George H.
Papachristodoulou, Antonis
author_facet Sootla, Aivar
Delalez, Nicolas
Alexis, Emmanouil
Norman, Arthur
Steel, Harrison
Wadhams, George H.
Papachristodoulou, Antonis
author_sort Sootla, Aivar
collection PubMed
description We introduce a new design framework for implementing negative feedback regulation in synthetic biology, which we term ‘dichotomous feedback’. Our approach is different from current methods, in that it sequesters existing fluxes in the process to be controlled, and in this way takes advantage of the process’s architecture to design the control law. This signal sequestration mechanism appears in many natural biological systems and can potentially be easier to realize than ‘molecular sequestration’ and other comparison motifs that are nowadays common in biomolecular feedback control design. The loop is closed by linking the strength of signal sequestration to the process output. Our feedback regulation mechanism is motivated by two-component signalling systems, where a second response regulator could be competing with the natural response regulator thus sequestering kinase activity. Here, dichotomous feedback is established by increasing the concentration of the second response regulator as the level of the output of the natural process increases. Extensive analysis demonstrates how this type of feedback shapes the signal response, attenuates intrinsic noise while increasing robustness and reducing crosstalk.
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spelling pubmed-90195192022-04-20 Dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design Sootla, Aivar Delalez, Nicolas Alexis, Emmanouil Norman, Arthur Steel, Harrison Wadhams, George H. Papachristodoulou, Antonis J R Soc Interface Life Sciences–Engineering interface We introduce a new design framework for implementing negative feedback regulation in synthetic biology, which we term ‘dichotomous feedback’. Our approach is different from current methods, in that it sequesters existing fluxes in the process to be controlled, and in this way takes advantage of the process’s architecture to design the control law. This signal sequestration mechanism appears in many natural biological systems and can potentially be easier to realize than ‘molecular sequestration’ and other comparison motifs that are nowadays common in biomolecular feedback control design. The loop is closed by linking the strength of signal sequestration to the process output. Our feedback regulation mechanism is motivated by two-component signalling systems, where a second response regulator could be competing with the natural response regulator thus sequestering kinase activity. Here, dichotomous feedback is established by increasing the concentration of the second response regulator as the level of the output of the natural process increases. Extensive analysis demonstrates how this type of feedback shapes the signal response, attenuates intrinsic noise while increasing robustness and reducing crosstalk. The Royal Society 2022-04-20 /pmc/articles/PMC9019519/ /pubmed/35440202 http://dx.doi.org/10.1098/rsif.2021.0737 Text en © 2022 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Life Sciences–Engineering interface
Sootla, Aivar
Delalez, Nicolas
Alexis, Emmanouil
Norman, Arthur
Steel, Harrison
Wadhams, George H.
Papachristodoulou, Antonis
Dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design
title Dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design
title_full Dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design
title_fullStr Dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design
title_full_unstemmed Dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design
title_short Dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design
title_sort dichotomous feedback: a signal sequestration-based feedback mechanism for biocontroller design
topic Life Sciences–Engineering interface
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019519/
https://www.ncbi.nlm.nih.gov/pubmed/35440202
http://dx.doi.org/10.1098/rsif.2021.0737
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