Model-based analysis of interferon-beta induced signaling pathway.

Bioinformatics
Jaroslaw SmiejaMarek Kimmel

Abstract

Interferon-beta induced JAK-STAT signaling pathways contribute to mucosal immune recognition and an anti-viral state. Though the main molecular mechanisms constituting these pathways are known, neither the detailed structure of the regulatory network, nor its dynamics has yet been investigated. The objective of this work is to build a mathematical model for the pathway that would serve two purposes: (1) to reproduce experimental results in simulation of both early and late response to Interferon-beta stimulation and (2) to explain experimental phenomena generating new hypotheses about regulatory mechanisms that cannot yet be tested experimentally. Experimentally determined time dependent changes in the major components of this pathway were used to build a mathematical model describing pathway dynamics in the form of ordinary differential equations. The experimental results suggested existence of unknown negative control mechanisms that were tested numerically using the model. Together, experimental and numerical data show that the epithelial JAK-STAT pathway might be subjected to previously unknown dynamic negative control mechanisms: (1) activation of dormant phosphatases and (2) inhibition of nuclear import of IRF1.

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Citations

Apr 25, 2012·Immunologic Research·Vipin NarangAlexandre Gouaillard
Jul 11, 2013·BMC Systems Biology·Inna PertsovskayaPablo Villoslada
Oct 20, 2010·International Journal of Molecular Sciences·Ildefonso Martínez de la Fuente
Jul 6, 2014·Current Infectious Disease Reports·Daire O'SheaAdrian Egli
Jun 9, 2012·Journal of Theoretical Biology·Mikołaj Rybiński, Anna Gambin
Oct 15, 2009·European Journal of Pharmacology·Andrzej SwierniakJaroslaw Smieja
Oct 5, 2013·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Wei Zhang, Xiufen Zou
Sep 27, 2013·JAK-STAT·Anna GambinMikołaj Rybiński
May 12, 2012·Journal of Theoretical Biology·Aylin Günel
Apr 4, 2017·PLoS Computational Biology·Irene Otero-MurasJoerg Stelling
Oct 25, 2016·Journal of Pharmacokinetics and Pharmacodynamics·Sihem Ait-Oudhia, Donald E Mager
Nov 6, 2018·Nature Communications·Tomasz JetkaMichał Komorowski
May 22, 2021·Expert Review of Proteomics·Morgan Mann, Allan R Brasier
Aug 9, 2021·Trends in Immunology·Laura C Van EyndhovenJurjen Tel

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