Trade-offs in Robustness to Perturbations of Bacterial Population Controllers *

Synthetic biology applications have the potential to have lasting impact; however, there is considerable difficulty in scaling up engineered genetic circuits. One of the current hurdles is resource sharing, where different circuit components become implicitly coupled through the host cell's poo...

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Main Authors: McBride, Cameron, Del Vecchio, Domitilla
Format: Article
Language:English
Published: Institute of Electrical and Electronics Engineers (IEEE) 2021
Online Access:https://hdl.handle.net/1721.1/138544
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author McBride, Cameron
Del Vecchio, Domitilla
author_facet McBride, Cameron
Del Vecchio, Domitilla
author_sort McBride, Cameron
collection MIT
description Synthetic biology applications have the potential to have lasting impact; however, there is considerable difficulty in scaling up engineered genetic circuits. One of the current hurdles is resource sharing, where different circuit components become implicitly coupled through the host cell's pool of resources, which may destroy circuit function. One potential solution around this problem is to distribute genetic circuit components across multiple cell strains and control the cell population size using a population controller. In these situations, perturbations in the availability of cellular resources, such as due to resource sharing, will affect the performance of the population controller. In this work, we model a genetic population controller implemented by a genetic circuit while considering perturbations in the availability of cellular resources. We analyze how these intracellular perturbations and extracellular disturbances to cell growth affect cell population size. We find that it is not possible to tune the population controller's gain such that the population density is robust to both extracellular disturbances and perturbations to the pool of available resources.
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spelling mit-1721.1/1385442021-12-18T03:01:37Z Trade-offs in Robustness to Perturbations of Bacterial Population Controllers * McBride, Cameron Del Vecchio, Domitilla Synthetic biology applications have the potential to have lasting impact; however, there is considerable difficulty in scaling up engineered genetic circuits. One of the current hurdles is resource sharing, where different circuit components become implicitly coupled through the host cell's pool of resources, which may destroy circuit function. One potential solution around this problem is to distribute genetic circuit components across multiple cell strains and control the cell population size using a population controller. In these situations, perturbations in the availability of cellular resources, such as due to resource sharing, will affect the performance of the population controller. In this work, we model a genetic population controller implemented by a genetic circuit while considering perturbations in the availability of cellular resources. We analyze how these intracellular perturbations and extracellular disturbances to cell growth affect cell population size. We find that it is not possible to tune the population controller's gain such that the population density is robust to both extracellular disturbances and perturbations to the pool of available resources. 2021-12-17T17:37:06Z 2021-12-17T17:37:06Z 2020 2021-12-17T17:34:40Z Article http://purl.org/eprint/type/ConferencePaper https://hdl.handle.net/1721.1/138544 McBride, Cameron and Del Vecchio, Domitilla. 2020. "Trade-offs in Robustness to Perturbations of Bacterial Population Controllers *." Proceedings of the American Control Conference, 2020-July. en 10.23919/ACC45564.2020.9148039 Proceedings of the American Control Conference 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 McBride, Cameron
Del Vecchio, Domitilla
Trade-offs in Robustness to Perturbations of Bacterial Population Controllers *
title Trade-offs in Robustness to Perturbations of Bacterial Population Controllers *
title_full Trade-offs in Robustness to Perturbations of Bacterial Population Controllers *
title_fullStr Trade-offs in Robustness to Perturbations of Bacterial Population Controllers *
title_full_unstemmed Trade-offs in Robustness to Perturbations of Bacterial Population Controllers *
title_short Trade-offs in Robustness to Perturbations of Bacterial Population Controllers *
title_sort trade offs in robustness to perturbations of bacterial population controllers
url https://hdl.handle.net/1721.1/138544
work_keys_str_mv AT mcbridecameron tradeoffsinrobustnesstoperturbationsofbacterialpopulationcontrollers
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