Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast

Autores
Schaber, Jörg; Baltanas, Rodrigo; Bush, Alan; Klipp, Edda; Colman Lerner, Alejandro Ariel
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The high osmolarity glycerol (HOG) pathway in yeast serves as a prototype signalling system foreukaryotes. We used an unprecedented amount of data to parameterise 192 models capturingdifferent hypotheses about molecular mechanisms underlying osmo-adaptation and selected a bestapproximating model. This model implied novel mechanisms regulating osmo-adaptation in yeast.The model suggested that (i) the main mechanism for osmo-adaptation is a fast and transient nontranscriptionalHog1-mediated activation of glycerol production, (ii) the transcriptional responseserves to maintain an increased steady-state glycerol production with lowsteady-state Hog1 activity,and (iii) fast negative feedbacks of activated Hog1 on upstream signalling branches serves tostabilise adaptation response. The best approximating model also indicated that homoeostaticadaptive systems with two parallel redundant signalling branches show a more robust and fasterresponse than single-branch systems. We corroborated this notion to a large extent by dedicatedmeasurements of volume recovery in single cells. Our study also demonstrates that systematicallytesting a model ensemble against data has the potential to achieve a better and unbiasedunderstanding of molecular mechanisms.
Fil: Schaber, Jörg. Institute For Experimental Internal Medicine; Alemania
Fil: Baltanas, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Bush, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Klipp, Edda. Humboldt-Universität zu Berlin; Alemania
Fil: Colman Lerner, Alejandro Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Materia
signal transduction
mathematical modeling
stress response
yeast
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/272667
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeastSchaber, JörgBaltanas, RodrigoBush, AlanKlipp, EddaColman Lerner, Alejandro Arielsignal transductionmathematical modelingstress responseyeasthttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The high osmolarity glycerol (HOG) pathway in yeast serves as a prototype signalling system foreukaryotes. We used an unprecedented amount of data to parameterise 192 models capturingdifferent hypotheses about molecular mechanisms underlying osmo-adaptation and selected a bestapproximating model. This model implied novel mechanisms regulating osmo-adaptation in yeast.The model suggested that (i) the main mechanism for osmo-adaptation is a fast and transient nontranscriptionalHog1-mediated activation of glycerol production, (ii) the transcriptional responseserves to maintain an increased steady-state glycerol production with lowsteady-state Hog1 activity,and (iii) fast negative feedbacks of activated Hog1 on upstream signalling branches serves tostabilise adaptation response. The best approximating model also indicated that homoeostaticadaptive systems with two parallel redundant signalling branches show a more robust and fasterresponse than single-branch systems. We corroborated this notion to a large extent by dedicatedmeasurements of volume recovery in single cells. Our study also demonstrates that systematicallytesting a model ensemble against data has the potential to achieve a better and unbiasedunderstanding of molecular mechanisms.Fil: Schaber, Jörg. Institute For Experimental Internal Medicine; AlemaniaFil: Baltanas, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Bush, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Klipp, Edda. Humboldt-Universität zu Berlin; AlemaniaFil: Colman Lerner, Alejandro Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaNature Publishing Group2012-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/272667Schaber, Jörg; Baltanas, Rodrigo; Bush, Alan; Klipp, Edda; Colman Lerner, Alejandro Ariel; Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast; Nature Publishing Group; Molecular Systems Biology; 8; 1; 11-2012; 1-171744-4292CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://msb.embopress.org/content/8/1/622.abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1038/msb.2012.53info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:00:56Zoai:ri.conicet.gov.ar:11336/272667instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:00:56.802CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast
title Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast
spellingShingle Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast
Schaber, Jörg
signal transduction
mathematical modeling
stress response
yeast
title_short Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast
title_full Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast
title_fullStr Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast
title_full_unstemmed Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast
title_sort Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast
dc.creator.none.fl_str_mv Schaber, Jörg
Baltanas, Rodrigo
Bush, Alan
Klipp, Edda
Colman Lerner, Alejandro Ariel
author Schaber, Jörg
author_facet Schaber, Jörg
Baltanas, Rodrigo
Bush, Alan
Klipp, Edda
Colman Lerner, Alejandro Ariel
author_role author
author2 Baltanas, Rodrigo
Bush, Alan
Klipp, Edda
Colman Lerner, Alejandro Ariel
author2_role author
author
author
author
dc.subject.none.fl_str_mv signal transduction
mathematical modeling
stress response
yeast
topic signal transduction
mathematical modeling
stress response
yeast
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The high osmolarity glycerol (HOG) pathway in yeast serves as a prototype signalling system foreukaryotes. We used an unprecedented amount of data to parameterise 192 models capturingdifferent hypotheses about molecular mechanisms underlying osmo-adaptation and selected a bestapproximating model. This model implied novel mechanisms regulating osmo-adaptation in yeast.The model suggested that (i) the main mechanism for osmo-adaptation is a fast and transient nontranscriptionalHog1-mediated activation of glycerol production, (ii) the transcriptional responseserves to maintain an increased steady-state glycerol production with lowsteady-state Hog1 activity,and (iii) fast negative feedbacks of activated Hog1 on upstream signalling branches serves tostabilise adaptation response. The best approximating model also indicated that homoeostaticadaptive systems with two parallel redundant signalling branches show a more robust and fasterresponse than single-branch systems. We corroborated this notion to a large extent by dedicatedmeasurements of volume recovery in single cells. Our study also demonstrates that systematicallytesting a model ensemble against data has the potential to achieve a better and unbiasedunderstanding of molecular mechanisms.
Fil: Schaber, Jörg. Institute For Experimental Internal Medicine; Alemania
Fil: Baltanas, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Bush, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Klipp, Edda. Humboldt-Universität zu Berlin; Alemania
Fil: Colman Lerner, Alejandro Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
description The high osmolarity glycerol (HOG) pathway in yeast serves as a prototype signalling system foreukaryotes. We used an unprecedented amount of data to parameterise 192 models capturingdifferent hypotheses about molecular mechanisms underlying osmo-adaptation and selected a bestapproximating model. This model implied novel mechanisms regulating osmo-adaptation in yeast.The model suggested that (i) the main mechanism for osmo-adaptation is a fast and transient nontranscriptionalHog1-mediated activation of glycerol production, (ii) the transcriptional responseserves to maintain an increased steady-state glycerol production with lowsteady-state Hog1 activity,and (iii) fast negative feedbacks of activated Hog1 on upstream signalling branches serves tostabilise adaptation response. The best approximating model also indicated that homoeostaticadaptive systems with two parallel redundant signalling branches show a more robust and fasterresponse than single-branch systems. We corroborated this notion to a large extent by dedicatedmeasurements of volume recovery in single cells. Our study also demonstrates that systematicallytesting a model ensemble against data has the potential to achieve a better and unbiasedunderstanding of molecular mechanisms.
publishDate 2012
dc.date.none.fl_str_mv 2012-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/272667
Schaber, Jörg; Baltanas, Rodrigo; Bush, Alan; Klipp, Edda; Colman Lerner, Alejandro Ariel; Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast; Nature Publishing Group; Molecular Systems Biology; 8; 1; 11-2012; 1-17
1744-4292
CONICET Digital
CONICET
url http://hdl.handle.net/11336/272667
identifier_str_mv Schaber, Jörg; Baltanas, Rodrigo; Bush, Alan; Klipp, Edda; Colman Lerner, Alejandro Ariel; Modelling reveals novel roles of two parallel signalling pathways and homeostatic feedbacks in yeast; Nature Publishing Group; Molecular Systems Biology; 8; 1; 11-2012; 1-17
1744-4292
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://msb.embopress.org/content/8/1/622.abstract
info:eu-repo/semantics/altIdentifier/doi/10.1038/msb.2012.53
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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