Introducing Spatial Information into Predictive NF-kappa B Modelling - An Agent-Based Approach

Authored by Mike Holcombe, Rod Smallwood, Mark Pogson, Eva Qwarnstrom

Date Published: 2008-06-04

DOI: 10.1371/journal.pone.0002367

Sponsors: Biotechnology and Biological Sciences Research Council (BBSRC) United Kingdom Engineering and Physical Sciences Research Council (EPSRC)

Platforms: No platforms listed

Model Documentation: Other Narrative

Model Code URLs: Model code not found

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-kappa B 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-kappa B is directly affected by actin filaments of the cytoskeleton sequestering excess inhibitors, therefore regulating steady-state and feedback behaviour.

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