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    ABSTRACT: Adaptive signalling is a common and important element in cellular systems. Threshold processes are also ubiquitous in signal transduction. This study takes a modular systems approach to systematically understand the interaction of adaptive modules and threshold modules (both monostable and bistable). The authors employ representative modules of adaptive and threshold elements and use these to examine and analyse various aspects of their interaction including the order of interconnection, the role of relative time scales, the difference between monostable and bistable thresholds in this context and how threshold modules may act as a switch induced by transient signals. Numerical simulations, bifurcation analysis and analytical work are employed to address these questions. Overall, the authors' analysis is a first step towards a detailed systems engineering understanding of the different kinds of interactions between these ubiquitous elements in cellular signal transduction. [Includes supplementary material].
    No preview · Article · Mar 2011 · IET Systems Biology
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    ABSTRACT: Translation is the final stage of gene expression where messenger RNA is used as a template for protein polymerization from appropriate amino acids. Release of the completed protein requires a release factor protein acting at the termination/stop codon to liberate it. In this paper we focus on a complex feedback control mechanism involved in the translation and synthesis of release factor proteins, which has been observed in different systems. These release factor proteins are involved in the termination stage of their own translation. Further, mutations in the release factor gene can result in a premature stop codon. In this case translation can result either in early termination and the production of a truncated protein or readthrough of the premature stop codon and production of the complete release factor protein. Thus during translation of the release factor mRNA containing a premature stop codon, the full length protein negatively regulates its production by its action on a premature stop codon, while positively regulating its production by its action on the regular stop codon. This paper develops a mathematical modelling framework to investigate this complex feedback control system involved in translation. A series of models is established to carefully investigate the role of individual mechanisms and how they work together. The steady state and dynamic behaviour of the resulting models are examined both analytically and numerically.
    Full-text · Article · Feb 2010 · Journal of Theoretical Biology
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