An N-stage cascade of phosphorylation cycles as an insulation device for synthetic biological circuits

Single phosphorylation cycles have been found to have insulation device abilities, that is, they attenuate the effect of retroactivity applied by downstream systems and hence facilitate modular design in synthetic biology. It was recently discovered that this retroactivity attenuation property comes...

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Main Authors: Shah, Rushina Jaidip, Del Vecchio, Domitilla
Other Authors: Massachusetts Institute of Technology. Department of Mechanical Engineering
Format: Article
Published: Institute of Electrical and Electronics Engineers (IEEE) 2018
Online Access:http://hdl.handle.net/1721.1/119153
https://orcid.org/0000-0002-5322-8303
https://orcid.org/0000-0001-6472-8576
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author Shah, Rushina Jaidip
Del Vecchio, Domitilla
author2 Massachusetts Institute of Technology. Department of Mechanical Engineering
author_facet Massachusetts Institute of Technology. Department of Mechanical Engineering
Shah, Rushina Jaidip
Del Vecchio, Domitilla
author_sort Shah, Rushina Jaidip
collection MIT
description Single phosphorylation cycles have been found to have insulation device abilities, that is, they attenuate the effect of retroactivity applied by downstream systems and hence facilitate modular design in synthetic biology. It was recently discovered that this retroactivity attenuation property comes at the expense of an increased retroactivity to the input of the insulation device, wherein the device slows down the signal it receives from its upstream system. In this paper, we demonstrate that insulation devices built of cascaded phosphorylation cycles can break this tradeoff, allowing to attenuate the retroactivity applied by downstream systems while keeping a small retroactivity to the input. In particular, we show that there is an optimal number of cycles that maximally extends the linear operating region of the insulation device while keeping the desired retroactivity properties, when a common phosphatase is used. These findings provide optimal design strategies of insulation devices for synthetic biology applications.
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spelling mit-1721.1/1191532022-10-02T06:33:02Z An N-stage cascade of phosphorylation cycles as an insulation device for synthetic biological circuits Shah, Rushina Jaidip Del Vecchio, Domitilla Massachusetts Institute of Technology. Department of Mechanical Engineering Shah, Rushina Jaidip Del Vecchio, Domitilla Single phosphorylation cycles have been found to have insulation device abilities, that is, they attenuate the effect of retroactivity applied by downstream systems and hence facilitate modular design in synthetic biology. It was recently discovered that this retroactivity attenuation property comes at the expense of an increased retroactivity to the input of the insulation device, wherein the device slows down the signal it receives from its upstream system. In this paper, we demonstrate that insulation devices built of cascaded phosphorylation cycles can break this tradeoff, allowing to attenuate the retroactivity applied by downstream systems while keeping a small retroactivity to the input. In particular, we show that there is an optimal number of cycles that maximally extends the linear operating region of the insulation device while keeping the desired retroactivity properties, when a common phosphatase is used. These findings provide optimal design strategies of insulation devices for synthetic biology applications. National Institutes of Health (U.S.) (NIH P50 GMO98792) 2018-11-16T18:21:28Z 2018-11-16T18:21:28Z 2016-07 2018-11-09T18:05:08Z Article http://purl.org/eprint/type/ConferencePaper 978-1-5090-2591-6 978-1-5090-2590-9 978-1-5090-2592-3 http://hdl.handle.net/1721.1/119153 Shah, Rushina, and Domitilla Del Vecchio. “An N-Stage Cascade of Phosphorylation Cycles as an Insulation Device for Synthetic Biological Circuits.” 2016 European Control Conference (ECC) (June 2016), Aalborg, Denmark, Institute of Electrical and Electronics Engineers (IEEE), 2016. © 2016 EUCA https://orcid.org/0000-0002-5322-8303 https://orcid.org/0000-0001-6472-8576 http://dx.doi.org/10.1109/ECC.2016.7810557 2016 European Control Conference (ECC) Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Institute of Electrical and Electronics Engineers (IEEE) MIT Web Domain
spellingShingle Shah, Rushina Jaidip
Del Vecchio, Domitilla
An N-stage cascade of phosphorylation cycles as an insulation device for synthetic biological circuits
title An N-stage cascade of phosphorylation cycles as an insulation device for synthetic biological circuits
title_full An N-stage cascade of phosphorylation cycles as an insulation device for synthetic biological circuits
title_fullStr An N-stage cascade of phosphorylation cycles as an insulation device for synthetic biological circuits
title_full_unstemmed An N-stage cascade of phosphorylation cycles as an insulation device for synthetic biological circuits
title_short An N-stage cascade of phosphorylation cycles as an insulation device for synthetic biological circuits
title_sort n stage cascade of phosphorylation cycles as an insulation device for synthetic biological circuits
url http://hdl.handle.net/1721.1/119153
https://orcid.org/0000-0002-5322-8303
https://orcid.org/0000-0001-6472-8576
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