Multi-time-scale biomolecular ‘quasi-integral’ controllers for set-point regulation and trajectory tracking

Recent trends in synthetic biology to move from prototypes to applications have triggered higher expectations on the robustness, predictability and responsiveness of biomolecular circuits. Therefore, a systematic approach to designing biomolecular controllers for regulating gene expression is needed...

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Main Authors: Qian, Yili, Grunberg, Theodore Wu, 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/1721.1/119164
https://orcid.org/0000-0002-1097-0401
https://orcid.org/0000-0001-6472-8576
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author Qian, Yili
Grunberg, Theodore Wu
Del Vecchio, Domitilla
author2 Massachusetts Institute of Technology. Department of Mechanical Engineering
author_facet Massachusetts Institute of Technology. Department of Mechanical Engineering
Qian, Yili
Grunberg, Theodore Wu
Del Vecchio, Domitilla
author_sort Qian, Yili
collection MIT
description Recent trends in synthetic biology to move from prototypes to applications have triggered higher expectations on the robustness, predictability and responsiveness of biomolecular circuits. Therefore, a systematic approach to designing biomolecular controllers for regulating gene expression is needed. Although a number of integral control motifs (ICMs) have been proposed for set-point regulation, their performance in vivo is challenged by integration leakiness due to dilution, which cannot be neglected in growing cells. In this paper, we study a class of quasi-integral controllers designed based on existing ICMs and multiple time-scale separations. We demonstrate that by engineering all controller reactions to be much faster than dilution, set-point regulation can be achieved even in the presence of a leaky integrator. Furthermore, by engineering controller parameters for a second layer of time-scale separation, arbitrarily small tracking error can be achieved under certain technical conditions. We demonstrate a realization of our design principle through a small RNA feedback circuit.
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spelling mit-1721.1/1191642022-10-02T04:44:21Z Multi-time-scale biomolecular ‘quasi-integral’ controllers for set-point regulation and trajectory tracking Qian, Yili Grunberg, Theodore Wu Del Vecchio, Domitilla Massachusetts Institute of Technology. Department of Mechanical Engineering Qian, Yili Grunberg, Theodore Wu Del Vecchio, Domitilla Recent trends in synthetic biology to move from prototypes to applications have triggered higher expectations on the robustness, predictability and responsiveness of biomolecular circuits. Therefore, a systematic approach to designing biomolecular controllers for regulating gene expression is needed. Although a number of integral control motifs (ICMs) have been proposed for set-point regulation, their performance in vivo is challenged by integration leakiness due to dilution, which cannot be neglected in growing cells. In this paper, we study a class of quasi-integral controllers designed based on existing ICMs and multiple time-scale separations. We demonstrate that by engineering all controller reactions to be much faster than dilution, set-point regulation can be achieved even in the presence of a leaky integrator. Furthermore, by engineering controller parameters for a second layer of time-scale separation, arbitrarily small tracking error can be achieved under certain technical conditions. We demonstrate a realization of our design principle through a small RNA feedback circuit. United States. Air Force. Office of Scientific Research (grant FA9550-14-1-0060) National Institutes of Health (U.S.). Civil, Mechanical and Manufacturing Innovation (award # 1727189) 2018-11-16T21:27:07Z 2018-11-16T21:27:07Z 2018-06 2018-11-09T15:55:47Z Article http://purl.org/eprint/type/ConferencePaper 978-1-5386-5428-6 978-1-5386-5427-9 978-1-5386-5429-3 2378-5861 http://hdl.handle.net/1721.1/119164 Qian, Yili, Theodore W. Grunberg, and Domitilla Del Vecchio. “Multi-Time-Scale Biomolecular ‘quasi-Integral’ Controllers for Set-Point Regulation and Trajectory Tracking.” 2018 Annual American Control Conference (ACC) (June 2018), ilwaukee, WI, USA, Institute of Electrical and Electronics Engineers (IEEE), 2018. https://orcid.org/0000-0002-1097-0401 https://orcid.org/0000-0001-6472-8576 http://dx.doi.org/10.23919/ACC.2018.8431762 American Control Conference (ACC), 2018 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 Qian, Yili
Grunberg, Theodore Wu
Del Vecchio, Domitilla
Multi-time-scale biomolecular ‘quasi-integral’ controllers for set-point regulation and trajectory tracking
title Multi-time-scale biomolecular ‘quasi-integral’ controllers for set-point regulation and trajectory tracking
title_full Multi-time-scale biomolecular ‘quasi-integral’ controllers for set-point regulation and trajectory tracking
title_fullStr Multi-time-scale biomolecular ‘quasi-integral’ controllers for set-point regulation and trajectory tracking
title_full_unstemmed Multi-time-scale biomolecular ‘quasi-integral’ controllers for set-point regulation and trajectory tracking
title_short Multi-time-scale biomolecular ‘quasi-integral’ controllers for set-point regulation and trajectory tracking
title_sort multi time scale biomolecular quasi integral controllers for set point regulation and trajectory tracking
url http://hdl.handle.net/1721.1/119164
https://orcid.org/0000-0002-1097-0401
https://orcid.org/0000-0001-6472-8576
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