Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy

Although blood sampling and medical imaging are well-established techniques in clinical diagnostics, they often require long post-processing procedures. Fast and simple quantification of signaling molecules can enable efficient health monitoring and improve diagnoses. Thyroid hormones (THs) treatmen...

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Authors: Martí Baena, Quim, Pascuet Fontanet, Andreu, Berjaga Buisan, Tomas, Caravaca Rodríguez, Miriam, Puig Costa-Jussà, Jaume, Sánchez Mejías, Avencia, Ivančić, Dimitrije, Mogas Díez, Sira, Güell Cargol, Marc, 1982-, Macía, Javier
Format: article
Status:Published version
Publication Date:2024
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/60748
Online Access:http://hdl.handle.net/10230/60748
http://dx.doi.org/10.3389/fsysb.2024.1270071
Access Level:Open access
Keyword:Synthetic biology
Mathematical modeling
Hypothyroidism
Thyroid hormones
Biosensor
Intein
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spelling Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapyMartí Baena, QuimPascuet Fontanet, AndreuBerjaga Buisan, TomasCaravaca Rodríguez, MiriamPuig Costa-Jussà, JaumeSánchez Mejías, AvenciaIvančić, DimitrijeMogas Díez, SiraGüell Cargol, Marc, 1982-Macía, JavierSynthetic biologyMathematical modelingHypothyroidismThyroid hormonesBiosensorInteinAlthough blood sampling and medical imaging are well-established techniques in clinical diagnostics, they often require long post-processing procedures. Fast and simple quantification of signaling molecules can enable efficient health monitoring and improve diagnoses. Thyroid hormones (THs) treatment relies on trial-and-error dose adjustments, and requires constant tracking via blood tests. Thus, a fast and reliable method that can constantly track THs levels could substantially improve patient quality of life by reducing their visits to doctors. Synthetic biosensors have shown to be inexpensive and easy tools for sensing molecules, with their use in healthcare increasing over time. This study describes the construction of an engineered THs bacterial biosensor, consisting of a split-intein-based TH receptor ligand binding domain (LBD) biosensor that reconstitutes green fluorescence protein (GFP) after binding to TH. This biosensor could quantitatively measure THs concentrations by evaluating fluorescence intensity. In vitro sensing using Escherichia coli produced GFP over a wide dynamic range. The biosensor was further optimized by adding a double LBD, which enhanced its dynamic range until it reached healthy physiological conditions. Moreover, a mathematical model was developed to assess the dynamic properties of the biosensor and to provide a basis for the characterization of other intein-mediated biosensors. This type of biosensor can be used as the basis for novel treatments of thyroid diseases and can be adapted to measure the concentrations of other hormones, giving rise to a series of mathematically characterized modular biosensors.Funding for this study and for the open access charge was in the form of grants from the Spanish Ministry of Economy and Competitiveness (MINECO PID 2020-119538RB-I00). This work was supported by “Unidad de Excelencia María de Maeztu” and funded by the AEI (CEX 2018-000792-M).Frontiers202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/60748http://dx.doi.org/10.3389/fsysb.2024.1270071reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésFront Syst Biol. 2024;4:1270071info:eu-repo/grantAgreement/ES/2PE/PID2020-119538RB-I00info:eu-repo/grantAgreement/ES/2PE/CEX2018-000792-M© 2024 Martí-Baena, Pascuet-Fontanet, Berjaga-Buisan, Caravaca-Rodríguez, Puig-Costa-Jussà, Sanchez-Mejias, Ivančić, Mogas-Díez, Güell and Macia. 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/http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/607482026-05-29T05:05:01Z
dc.title.none.fl_str_mv Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy
title Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy
spellingShingle Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy
Martí Baena, Quim
Synthetic biology
Mathematical modeling
Hypothyroidism
Thyroid hormones
Biosensor
Intein
title_short Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy
title_full Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy
title_fullStr Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy
title_full_unstemmed Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy
title_sort Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy
dc.creator.none.fl_str_mv Martí Baena, Quim
Pascuet Fontanet, Andreu
Berjaga Buisan, Tomas
Caravaca Rodríguez, Miriam
Puig Costa-Jussà, Jaume
Sánchez Mejías, Avencia
Ivančić, Dimitrije
Mogas Díez, Sira
Güell Cargol, Marc, 1982-
Macía, Javier
author Martí Baena, Quim
author_facet Martí Baena, Quim
Pascuet Fontanet, Andreu
Berjaga Buisan, Tomas
Caravaca Rodríguez, Miriam
Puig Costa-Jussà, Jaume
Sánchez Mejías, Avencia
Ivančić, Dimitrije
Mogas Díez, Sira
Güell Cargol, Marc, 1982-
Macía, Javier
author_role author
author2 Pascuet Fontanet, Andreu
Berjaga Buisan, Tomas
Caravaca Rodríguez, Miriam
Puig Costa-Jussà, Jaume
Sánchez Mejías, Avencia
Ivančić, Dimitrije
Mogas Díez, Sira
Güell Cargol, Marc, 1982-
Macía, Javier
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Synthetic biology
Mathematical modeling
Hypothyroidism
Thyroid hormones
Biosensor
Intein
topic Synthetic biology
Mathematical modeling
Hypothyroidism
Thyroid hormones
Biosensor
Intein
description Although blood sampling and medical imaging are well-established techniques in clinical diagnostics, they often require long post-processing procedures. Fast and simple quantification of signaling molecules can enable efficient health monitoring and improve diagnoses. Thyroid hormones (THs) treatment relies on trial-and-error dose adjustments, and requires constant tracking via blood tests. Thus, a fast and reliable method that can constantly track THs levels could substantially improve patient quality of life by reducing their visits to doctors. Synthetic biosensors have shown to be inexpensive and easy tools for sensing molecules, with their use in healthcare increasing over time. This study describes the construction of an engineered THs bacterial biosensor, consisting of a split-intein-based TH receptor ligand binding domain (LBD) biosensor that reconstitutes green fluorescence protein (GFP) after binding to TH. This biosensor could quantitatively measure THs concentrations by evaluating fluorescence intensity. In vitro sensing using Escherichia coli produced GFP over a wide dynamic range. The biosensor was further optimized by adding a double LBD, which enhanced its dynamic range until it reached healthy physiological conditions. Moreover, a mathematical model was developed to assess the dynamic properties of the biosensor and to provide a basis for the characterization of other intein-mediated biosensors. This type of biosensor can be used as the basis for novel treatments of thyroid diseases and can be adapted to measure the concentrations of other hormones, giving rise to a series of mathematically characterized modular biosensors.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
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/10230/60748
http://dx.doi.org/10.3389/fsysb.2024.1270071
url http://hdl.handle.net/10230/60748
http://dx.doi.org/10.3389/fsysb.2024.1270071
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Front Syst Biol. 2024;4:1270071
info:eu-repo/grantAgreement/ES/2PE/PID2020-119538RB-I00
info:eu-repo/grantAgreement/ES/2PE/CEX2018-000792-M
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:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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