General analyses of gene expression dependencies on genetic burden

Over the last decade, the combining of newly developed molecular tools for DNA editing with engineering principles has allowed the creation of complex cellular devices, usually based on complex genetic circuits, for many different purposes. However, when the technological evolution of genetic circui...

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Detalles Bibliográficos
Autores: González Colell, Marc, Macía, Javier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/45408
Acceso en línea:http://hdl.handle.net/10230/45408
http://dx.doi.org/10.3389/fbioe.2020.01017
Access Level:acceso abierto
Palabra clave:Gene expression
Genetic burden
Gentic circuits
Mathematical model
Synthetic biological circuits
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spelling General analyses of gene expression dependencies on genetic burdenGonzález Colell, MarcMacía, JavierGene expressionGenetic burdenGentic circuitsMathematical modelSynthetic biological circuitsOver the last decade, the combining of newly developed molecular tools for DNA editing with engineering principles has allowed the creation of complex cellular devices, usually based on complex genetic circuits, for many different purposes. However, when the technological evolution of genetic circuitry is compared with previous technologies such as electronic circuitry, clear limitations regarding the technological scalability of genetic circuitry are observed due to the lack of predictability. To overcome this problem, it is necessary to create new theoretical frameworks for designing genetic circuits in a feasible and reliable manner, taking into account those limitations. Among a number of such limitations, the so-called genetic burden is one of the main constraints. Surprisingly, despite its relevance, little attention has been paid to genetic burden, and it is often not considered when designing genetic circuits. In this study, a new general mathematical formalism is presented, describing the effects of genetic burden on gene expression. The mathematical analysis shows that alterations in gene expression due to genetic burden can be qualitatively described independently of the specific genetic features of the system under consideration. The mathematical model was experimentally tested in different genetic circuits. The experimental evidence coincides with the expected behaviors described by the model in complex scenarios. For instance, observed modulations in the expression levels of constitutive genes in response to changes in the levels of external inducers of gene expression that do not directly modulate them, or the emergence of limitations in gene overexpression, can be understood in terms of genetic burden. The present mathematical formalism provides a useful general framework for gene circuit design that will help to advance synthetic biological systems.Frontiers202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/45408http://dx.doi.org/10.3389/fbioe.2020.01017reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésFront Bioeng Biotechnol. 2020; 8:1017© 2020 González-Colell and Macía. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/454082026-06-12T07:21:37Z
dc.title.none.fl_str_mv General analyses of gene expression dependencies on genetic burden
title General analyses of gene expression dependencies on genetic burden
spellingShingle General analyses of gene expression dependencies on genetic burden
González Colell, Marc
Gene expression
Genetic burden
Gentic circuits
Mathematical model
Synthetic biological circuits
title_short General analyses of gene expression dependencies on genetic burden
title_full General analyses of gene expression dependencies on genetic burden
title_fullStr General analyses of gene expression dependencies on genetic burden
title_full_unstemmed General analyses of gene expression dependencies on genetic burden
title_sort General analyses of gene expression dependencies on genetic burden
dc.creator.none.fl_str_mv González Colell, Marc
Macía, Javier
author González Colell, Marc
author_facet González Colell, Marc
Macía, Javier
author_role author
author2 Macía, Javier
author2_role author
dc.subject.none.fl_str_mv Gene expression
Genetic burden
Gentic circuits
Mathematical model
Synthetic biological circuits
topic Gene expression
Genetic burden
Gentic circuits
Mathematical model
Synthetic biological circuits
description Over the last decade, the combining of newly developed molecular tools for DNA editing with engineering principles has allowed the creation of complex cellular devices, usually based on complex genetic circuits, for many different purposes. However, when the technological evolution of genetic circuitry is compared with previous technologies such as electronic circuitry, clear limitations regarding the technological scalability of genetic circuitry are observed due to the lack of predictability. To overcome this problem, it is necessary to create new theoretical frameworks for designing genetic circuits in a feasible and reliable manner, taking into account those limitations. Among a number of such limitations, the so-called genetic burden is one of the main constraints. Surprisingly, despite its relevance, little attention has been paid to genetic burden, and it is often not considered when designing genetic circuits. In this study, a new general mathematical formalism is presented, describing the effects of genetic burden on gene expression. The mathematical analysis shows that alterations in gene expression due to genetic burden can be qualitatively described independently of the specific genetic features of the system under consideration. The mathematical model was experimentally tested in different genetic circuits. The experimental evidence coincides with the expected behaviors described by the model in complex scenarios. For instance, observed modulations in the expression levels of constitutive genes in response to changes in the levels of external inducers of gene expression that do not directly modulate them, or the emergence of limitations in gene overexpression, can be understood in terms of genetic burden. The present mathematical formalism provides a useful general framework for gene circuit design that will help to advance synthetic biological systems.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/45408
http://dx.doi.org/10.3389/fbioe.2020.01017
url http://hdl.handle.net/10230/45408
http://dx.doi.org/10.3389/fbioe.2020.01017
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Front Bioeng Biotechnol. 2020; 8:1017
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
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