Bridging the gap between modules in isolation and as part of networks: a systems framework for elucidating interaction and regulation of signalling modules
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Accepted version
Author(s)
Menon, G
Krishnan, J
Type
Journal Article
Abstract
While signalling and biochemical modules have been the focus of numerous studies, they are typically studied in isolation, with no examination of the effects of the ambient network. In this paper we formulate and develop a systems framework, rooted in dynamical systems, to understand such effects, by studying the interaction of signalling modules. The modules we consider are (i) basic covalent modification, (ii) monostable switches, (iii) bistable switches, (iv) adaptive modules, and (v) oscillatory modules. We systematically examine the interaction of these modules by analyzing (a) sequential interaction without shared components, (b) sequential interaction with shared components, and (c) oblique interactions. Our studies reveal that the behaviour of a module in isolation may be substantially different from that in a network, and explicitly demonstrate how the behaviour of a given module, the characteristics of the ambient network, and the possibility of shared components can result in new effects. Our global approach illuminates different aspects of the structure and functioning of modules, revealing the importance of dynamical characteristics as well as biochemical features; this provides a methodological platform for investigating the complexity of natural modules shaped by evolution, elucidating the effects of ambient networks on a module in multiple cellular contexts, and highlighting the capabilities and constraints for engineering robust synthetic modules. Overall, such a systems framework provides a platform for bridging the gap between non-linear information processing modules, in isolation and as parts of networks, and a basis for understanding new aspects of natural and engineered cellular networks.
Date Issued
2016-07-19
Date Acceptance
2016-06-02
Citation
Journal of Chemical Physics, 2016, 145
ISSN
1089-7690
Publisher
American Institute of Physics (AIP)
Journal / Book Title
Journal of Chemical Physics
Volume
145
Copyright Statement
Copyright © 2016 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in The Journal of Chemical Physics 145, 035103 (2016); doi: 10.1063/1.4953914 and may be found at https://dx.doi.org/10.1063/1.4953914.
Subjects
Chemical Physics
02 Physical Sciences
03 Chemical Sciences
09 Engineering
Publication Status
Published
Article Number
035103