%0 Journal Article
%T Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway
%A Maria Luisa Guerriero
%A Anna Dudka
%A Nicholas Underhill-Day
%A John K Heath
%A Corrado Priami
%J BMC Systems Biology
%D 2009
%I BioMed Central
%R 10.1186/1752-0509-3-40
%X Here we use a high-level narrative language in designing a computational model of the gp130/JAK/STAT signalling pathway and show that the model reproduces the dynamic behaviour of the pathway derived by biological observation. We then "experiment" on the model by simulation and sensitivity analysis to define those parameters which dominate the dynamic behaviour of the pathway. The model predicts that nuclear compartmentalisation and phosphorylation status of STAT are key determinants of the pathway and that alternative mechanisms of signal attenuation exert their influence on different timescales.The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself.Biological signalling pathways of even modest complexity cannot be comprehensively analysed within a feasible timescale by currently available experimental tools. However appropriate pathway models can be used to generate, explore and refine hypotheses guiding the formulation and prioritisation of experimental interventions. This has conventionally been approached by the use of models inspired by chemical kinetics and articulated mathematically in the form of ordinary differential equations. Recently an alternative approach, "molecules as computation", has been proposed in which a pathway is formulated as an executable computer programme [1,2] which can be interrogated to deter
%U http://www.biomedcentral.com/1752-0509/3/40