An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli

Autores
Corbat, Agustín Andrés; Silberberg, Mauro; Grecco, Hernan Edgardo
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Apoptosis, a form of programmed cell death central to all multicellular organisms, plays a key role during organism development and is often misregulated in cancer. Devising a single model applicable to distinct stimuli and conditions has been limited by lack of robust observables. Indeed, previous numerical models have been tailored to fit experimental datasets in restricted scenarios, failing to predict response to different stimuli. We quantified the activity of three caspases simultaneously upon intrinsic or extrinsic stimulation to assemble a comprehensive dataset. We measured and modeled the time between maximum activity of intrinsic, extrinsic and effector caspases, a robust observable of network dynamics, to create the first integrated Apoptotic Reaction Model (ARM). Observing how effector caspases reach maximum activity first irrespective of stimuli used, led us to identify and incorporate a missing feedback into a successful model for extrinsic stimulation. By simulating different recently performed experiments, we corroborated that ARM adequately describes them. This integrated model provides further insight into the indispensable feedback from effector caspase to initiator caspases.
Fil: Corbat, Agustín Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina
Fil: Silberberg, Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina
Fil: Grecco, Hernan Edgardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Max Planck Institute of Molecular Physiology; Alemania
Materia
APOPTOTIC NETWORK
CASPASE ACTIVITY
HOMO-FRET-BASED BIOSENSOR
MATHEMATICAL MODELING
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/182307
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuliCorbat, Agustín AndrésSilberberg, MauroGrecco, Hernan EdgardoAPOPTOTIC NETWORKCASPASE ACTIVITYHOMO-FRET-BASED BIOSENSORMATHEMATICAL MODELINGhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Apoptosis, a form of programmed cell death central to all multicellular organisms, plays a key role during organism development and is often misregulated in cancer. Devising a single model applicable to distinct stimuli and conditions has been limited by lack of robust observables. Indeed, previous numerical models have been tailored to fit experimental datasets in restricted scenarios, failing to predict response to different stimuli. We quantified the activity of three caspases simultaneously upon intrinsic or extrinsic stimulation to assemble a comprehensive dataset. We measured and modeled the time between maximum activity of intrinsic, extrinsic and effector caspases, a robust observable of network dynamics, to create the first integrated Apoptotic Reaction Model (ARM). Observing how effector caspases reach maximum activity first irrespective of stimuli used, led us to identify and incorporate a missing feedback into a successful model for extrinsic stimulation. By simulating different recently performed experiments, we corroborated that ARM adequately describes them. This integrated model provides further insight into the indispensable feedback from effector caspase to initiator caspases.Fil: Corbat, Agustín Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: Silberberg, Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: Grecco, Hernan Edgardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Max Planck Institute of Molecular Physiology; AlemaniaCold Spring Harbor Laboratory Press2021-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182307Corbat, Agustín Andrés; Silberberg, Mauro; Grecco, Hernan Edgardo; An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli; Cold Spring Harbor Laboratory Press; bioRxiv; 5-2021; 1-222692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2021.05.21.444824v1info:eu-repo/semantics/altIdentifier/doi/10.1101/2021.05.21.444824info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:24Zoai:ri.conicet.gov.ar:11336/182307instacron: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:34982025-09-29 09:36:24.473CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli
title An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli
spellingShingle An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli
Corbat, Agustín Andrés
APOPTOTIC NETWORK
CASPASE ACTIVITY
HOMO-FRET-BASED BIOSENSOR
MATHEMATICAL MODELING
title_short An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli
title_full An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli
title_fullStr An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli
title_full_unstemmed An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli
title_sort An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli
dc.creator.none.fl_str_mv Corbat, Agustín Andrés
Silberberg, Mauro
Grecco, Hernan Edgardo
author Corbat, Agustín Andrés
author_facet Corbat, Agustín Andrés
Silberberg, Mauro
Grecco, Hernan Edgardo
author_role author
author2 Silberberg, Mauro
Grecco, Hernan Edgardo
author2_role author
author
dc.subject.none.fl_str_mv APOPTOTIC NETWORK
CASPASE ACTIVITY
HOMO-FRET-BASED BIOSENSOR
MATHEMATICAL MODELING
topic APOPTOTIC NETWORK
CASPASE ACTIVITY
HOMO-FRET-BASED BIOSENSOR
MATHEMATICAL MODELING
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Apoptosis, a form of programmed cell death central to all multicellular organisms, plays a key role during organism development and is often misregulated in cancer. Devising a single model applicable to distinct stimuli and conditions has been limited by lack of robust observables. Indeed, previous numerical models have been tailored to fit experimental datasets in restricted scenarios, failing to predict response to different stimuli. We quantified the activity of three caspases simultaneously upon intrinsic or extrinsic stimulation to assemble a comprehensive dataset. We measured and modeled the time between maximum activity of intrinsic, extrinsic and effector caspases, a robust observable of network dynamics, to create the first integrated Apoptotic Reaction Model (ARM). Observing how effector caspases reach maximum activity first irrespective of stimuli used, led us to identify and incorporate a missing feedback into a successful model for extrinsic stimulation. By simulating different recently performed experiments, we corroborated that ARM adequately describes them. This integrated model provides further insight into the indispensable feedback from effector caspase to initiator caspases.
Fil: Corbat, Agustín Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina
Fil: Silberberg, Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina
Fil: Grecco, Hernan Edgardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina. Max Planck Institute of Molecular Physiology; Alemania
description Apoptosis, a form of programmed cell death central to all multicellular organisms, plays a key role during organism development and is often misregulated in cancer. Devising a single model applicable to distinct stimuli and conditions has been limited by lack of robust observables. Indeed, previous numerical models have been tailored to fit experimental datasets in restricted scenarios, failing to predict response to different stimuli. We quantified the activity of three caspases simultaneously upon intrinsic or extrinsic stimulation to assemble a comprehensive dataset. We measured and modeled the time between maximum activity of intrinsic, extrinsic and effector caspases, a robust observable of network dynamics, to create the first integrated Apoptotic Reaction Model (ARM). Observing how effector caspases reach maximum activity first irrespective of stimuli used, led us to identify and incorporate a missing feedback into a successful model for extrinsic stimulation. By simulating different recently performed experiments, we corroborated that ARM adequately describes them. This integrated model provides further insight into the indispensable feedback from effector caspase to initiator caspases.
publishDate 2021
dc.date.none.fl_str_mv 2021-05
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/11336/182307
Corbat, Agustín Andrés; Silberberg, Mauro; Grecco, Hernan Edgardo; An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli; Cold Spring Harbor Laboratory Press; bioRxiv; 5-2021; 1-22
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182307
identifier_str_mv Corbat, Agustín Andrés; Silberberg, Mauro; Grecco, Hernan Edgardo; An Integrative Apoptotic Reaction Model for extrinsic and intrinsic stimuli; Cold Spring Harbor Laboratory Press; bioRxiv; 5-2021; 1-22
2692-8205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2021.05.21.444824v1
info:eu-repo/semantics/altIdentifier/doi/10.1101/2021.05.21.444824
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
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 13.070432

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