TY - GEN
T1 - Investigating IKK dynamics in the NF-κB signalling pathway using X-Machines
AU - Williams, Richard A.
AU - Timmis, Jon
AU - Qwarnstrom, Eva E.
N1 - Funding Information:
ACKNOWLEDGMENT JT is part-funded by The Royal Society, The Royal Academy of Engineering, and the Engineering and Physical Sciences Research Council (Grant No. EP/K040820/1). The York Computational Immunology Laboratory is part-funded by the Wellcome Trust (Ref: 097829) through the Centre for Chronic Diseases and Disorders (C2D2) at the University of York. EEQ (The Cell Biology Laboratory in the Department of Infection, Immunity and Cardiovascular Disease, at the University of Sheffield) is part-funded by the Biotechnology and Biological Sciences Research Council (Grant No. BB/J009687/1) and the British Heart Foundation (Grant No. PG/11/103/29219).
Publisher Copyright:
© 2017 IEEE.
PY - 2017/7/5
Y1 - 2017/7/5
N2 - The transcription factor NF-κB is a biological component that is central to the regulation of genes involved in the innate immune system. 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. We have developed an agent-based model of the IL-1 stimulated NF-κB signalling pathway, which has been calibrated to wet-lab data at the single-cell level. Through rigorous software engineering, we believe our model provides an abstracted view of the underlying real-world system, and can be used in a predictive capacity through in silico experimentation. In this study, we have focused on the dynamics of the IKK complex and its activation of NF-κB. Our agent-based model suggests that the pathway is sensitive to: variations in the binding probability of IKK to the inhibited NF-κB-IκBα complex; and variations in the temporal rebinding delay of IKK.
AB - The transcription factor NF-κB is a biological component that is central to the regulation of genes involved in the innate immune system. 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. We have developed an agent-based model of the IL-1 stimulated NF-κB signalling pathway, which has been calibrated to wet-lab data at the single-cell level. Through rigorous software engineering, we believe our model provides an abstracted view of the underlying real-world system, and can be used in a predictive capacity through in silico experimentation. In this study, we have focused on the dynamics of the IKK complex and its activation of NF-κB. Our agent-based model suggests that the pathway is sensitive to: variations in the binding probability of IKK to the inhibited NF-κB-IκBα complex; and variations in the temporal rebinding delay of IKK.
UR - http://www.scopus.com/inward/record.url?scp=85027850438&partnerID=8YFLogxK
U2 - 10.1109/CEC.2017.7969320
DO - 10.1109/CEC.2017.7969320
M3 - Conference Proceeding (Non-Journal item)
AN - SCOPUS:85027850438
T3 - 2017 IEEE Congress on Evolutionary Computation, CEC 2017 - Proceedings
SP - 249
EP - 256
BT - 2017 IEEE Congress on Evolutionary Computation, CEC 2017 - Proceedings
PB - IEEE Press
T2 - 2017 IEEE Congress on Evolutionary Computation, CEC 2017
Y2 - 5 June 2017 through 8 June 2017
ER -