A mathematical modelling framework for understanding chemorepulsive signal transduction in Dictyostelium

2012

BMC Systems Biology

Self Cite

BackgroundSpatial signal transduction plays a vital role in many intracellular processes such as eukaryotic chemotaxis, polarity generation and cell division. Furthermore it is being increasingly realized that the spatial dimension to signalling may play an important role in other apparently purely temporal signal transduction processes. It is increasingly being recognized that a conceptual basis for studying spatial signal transduction in signalling networks is necessary.ResultsIn this work we examine spatial signal transduction in a series of standard motifs/networks. These networks include coherent and incoherent feedforward, positive and negative feedback, cyclic motifs, monostable switches, bistable switches and negative feedback oscillators. In all these cases, the driving signal has spatial variation. For each network we consider two cases, one where all elements are essentially non-diffusible, and the other where one of the network elements may be highly diffusible. A careful analysis of steady state signal transduction provides many insights into the behaviour of all these modules. While in the non-diffusible case for the most part, spatial signalling reflects the temporal signalling behaviour, in the diffusible cases, we see significant differences between spatial and temporal signalling characteristics. Our results demonstrate that the presence of diffusible elements in the networks provides important constraints and capabilities for signalling.ConclusionsOur results provide a systematic basis for understanding spatial signalling in networks and the role of diffusible elements therein. This provides many insights into the signal transduction capabilities and constraints in such networks and suggests ways in which cellular signalling and information processing is organized to conform to or bypass those constraints. It also provides a framework for starting to understand the organization and regulation of spatial signal transduction in individual processes.

Section: Introductionmentioning

confidence: 99%

An investigation of spatial signal transduction in cellular networks

Alam-Nazki¹,

2012

BMC Systems Biology

Self Cite

“…From the modelling perspective, a series of modelling efforts have been aimed at understanding signal transduction in chemoattraction in E.coli as well as eukaryotes (for example see (Tindall et al, 2008;Iglesias & Devreotes, 2008) for surveys of the relevant efforts). A mechanistic modelling study of chemorepulsive sensing in Dictyostelium was performed by us in a recent paper (Alam-Nazki & Krishnan, 2010).…”

Section: Introductionmentioning

confidence: 99%

An investigation of design principles underlying repulsive and attractive gradient sensing and their switching

Journal of Theoretical Biology

Alam-Nazki

2011

Self Cite

Cite this article as: J. Krishnan and Aiman Alam-Nazki, An investigation of design principles underlying repulsive and attractive gradient sensing and their switching, Journal of Theoretical Biology, doi:10.1016Biology, doi:10. /j.jtbi.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

The behaviour of basic autocatalytic signalling modules in isolation and embedded in networks

The Journal of Chemical Physics

Mois

Suwanmajo

2014

In this paper, we examine the behaviour of basic autocatalytic feedback modules involving a species catalyzing its own production, either directly or indirectly. We first perform a systematic study of the autocatalytic feedback module in isolation, examining the effect of different factors, showing how this module is capable of exhibiting monostable threshold and bistable switch-like behaviour. We then study the behaviour of this module embedded in different kinds of basic networks including (essentially) irreversible cycles, open and closed reversible chains, and networks with additional feedback. We study the behaviour of the networks deterministically and also stochastically, using simulations, analytical work, and bifurcation analysis. We find that (i) there are significant differences between the behaviour of this module in isolation and in a network: thresholds may be altered or destroyed and bistability may be destroyed or even induced, even when the ambient network is simple. The global characteristics and topology of this network and the position of the module in the ambient network can play important and unexpected roles. (ii) There can be important differences between the deterministic and stochastic dynamics of the module embedded in networks, which may be accentuated by the ambient network. This provides new insights into the functioning of such enzymatic modules individually and as part of networks, with relevance to other enzymatic signalling modules as well.