Introducing Spatial Information into Predictive NF-κB Modelling – An Agent-Based Approach
Open Access
- 4 June 2008
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 3 (6), e2367
- https://doi.org/10.1371/journal.pone.0002367
Abstract
Nature is governed by local interactions among lower-level sub-units, whether at the cell, organ, organism, or colony level. Adaptive system behaviour emerges via these interactions, which integrate the activity of the sub-units. To understand the system level it is necessary to understand the underlying local interactions. Successful models of local interactions at different levels of biological organisation, including epithelial tissue and ant colonies, have demonstrated the benefits of such ‘agent-based’ modelling [1]–[4]. Here we present an agent-based approach to modelling a crucial biological system – the intracellular NF-κB signalling pathway. The pathway is vital to immune response regulation, and is fundamental to basic survival in a range of species [5]–[7]. Alterations in pathway regulation underlie a variety of diseases, including atherosclerosis and arthritis. Our modelling of individual molecules, receptors and genes provides a more comprehensive outline of regulatory network mechanisms than previously possible with equation-based approaches [8]. The method also permits consideration of structural parameters in pathway regulation; here we predict that inhibition of NF-κB is directly affected by actin filaments of the cytoskeleton sequestering excess inhibitors, therefore regulating steady-state and feedback behaviour.Keywords
This publication has 20 references indexed in Scilit:
- Formal agent-based modelling of intracellular chemical interactionsBiosystems, 2006
- Trail geometry gives polarity to ant foraging networksNature, 2004
- Agent-Based Computational Modeling of Wounded Epithelial Cell MonolayersIEEE Transactions on Nanobioscience, 2004
- The epitheliome: agent-based modelling of the social behaviour of cellsBiosystems, 2004
- Coupled computational simulation and empirical research into the foraging system of Pharaoh’s ant (Monomorium pharaonis)Biosystems, 2004
- RelA Control of IκBα PhosphorylationPublished by Elsevier BV ,2003
- Overview of the Alliance for Cellular SignalingNature, 2002
- Dynamic Shuttling of Nuclear Factor κB between the Nucleus and Cytoplasm as a Consequence of Inhibitor DissociationPublished by Elsevier BV ,2000
- Activation of Nuclear Factor κB in Single Living CellsPublished by Elsevier BV ,1999
- I kappa B interacts with the nuclear localization sequences of the subunits of NF-kappa B: a mechanism for cytoplasmic retention.Genes & Development, 1992