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Analysis and extension of a biochemical network model using robust control theory

Kim, Jung-Su, Valeyev, Najl V., Postlethwaite, Ian, Heslop-Harrison, Pat, Cho, Ki-Ho, Bates, Declan G. (2010) Analysis and extension of a biochemical network model using robust control theory. International Journal of Robust and Nonlinear Control, 20 (9). pp. 1017-1026. ISSN 1049-8923. (doi:10.1002/rnc.1528) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1002/rnc.1528

Abstract

Mathematical models of biological processes which have been observed in vivo to be highly robust to intracellular and environmental variations should themselves display appropriate levels of robustness when analysed in silico. This paper uses techniques from robust control theory to analyse and extend a mathematical model of the interacting proteins underlying adenosine 3?, 5?-cyclic monophosphate (cAMP) oscillations in aggregating Dictyostelium cells. Starting with a previously proposed ‘minimal’ model, we show how robustness analysis using the structured singular value can identify points of structural fragility in the network. By combining these results with insights from recent results from the experimental literature, we show how the original model can be augmented with some important additional modules, comprising networks involving IP3 and Ca2+. By analysing the robustness of our new extended model, we are able to show that dynamic interactions between the different modules play a pivotal role in generating robust cAMP oscillations; thus, significantly improving our understanding of the design principles underlying this complex biological system.

Item Type: Article
DOI/Identification number: 10.1002/rnc.1528
Additional information: Special Issue: Focus on Robustness in Systems Biology: Methods and Applications
Uncontrolled keywords: robustness analysis;structured singular value;Dictyostelium;systems biology
Subjects: T Technology
Divisions: Faculties > Sciences > School of Engineering and Digital Arts
Depositing User: Tina Thompson
Date Deposited: 28 Oct 2013 16:42 UTC
Last Modified: 29 May 2019 11:11 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/35734 (The current URI for this page, for reference purposes)
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