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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2022
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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. |
format | Online Article Text |
id | pubmed-9019519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
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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