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  • NFkB_XMachines

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Towards a platform model of the IL-1 stimulated NF-kB signalling pathway using communicating stream X-machines

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The Nuclear Factor-kappa B (NF-κB) signalling pathway is one of the key signalling pathways involved in the control and regulation of the immune system [3]. Activation of the NF-κB transcription factor is a tightly regulated event, with NF-κB normally sequestered in the cytosol of non-stimulated cells. Following activation of a cell membrane receptor and propagation of the signal via intracellular signalling to the IκB Kinase (IKK), phosphorylation-induced degradation of IκB inhibitors occurs to facilitate the release of NF-κB and its translocation to the nucleus. Dysregulation of the pathway is known to be involved in a large number of inflammatory diseases.

Although considerable research has been performed since its discovery in 1986, we are still not in a position to control the signalling pathway, and thus limit the effects of NF-κB within promotion of inflammatory diseases. Through adherence to the CoSMoS framework, we are developing a computational model of the IL-1 stimulated NF-κB intracellular signalling pathway, to assist in promoting our understanding of the mechanistic behaviours within the signalling network, and therefore identify potential targets for therapeutic interventions. We have previously developed a separate domain model [4, 5] as advocated by the CoSMoS framework, which captures the essential processes and entities of the system under study using; in particular, the emergent behaviour, at an appropriate level of abstraction using a mixture of cartoon and UML diagrams, along with statistical techniques to define the temporal-spatial dynamics.