A mathematical modelling framework for understanding chemorepulsive signal transduction in Dictyostelium |
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Authors: | Aiman Alam-Nazki J. Krishnan |
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Affiliation: | a Department of Chemical Engineering and Chemical Technology, Imperial College London, South Kensington Campus, London SW7 2AZ, UKb Centre for Process Systems Engineering (CPSE), Imperial College London, South Kensington Campus, London SW7 2AZ, UKc Institute of Systems and Synthetic Biology, Imperial College London, South Kensington Campus, London SW7 2AZ, UK |
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Abstract: | Chemorepulsion is the process by which an organism or a cell moves in the direction of decreasing chemical concentration. While a few experimental studies have been performed, no mathematical models exist for this process. In this paper we have modelled gradient sensing, the first subprocess of chemorepulsion, in Dictyostelium discoideum-a well characterized model eukaryotic system. We take the first steps towards achieving a comprehensive mechanistic understanding of chemorepulsion in this system. We have used, as a basis, the biochemical network of the Keizer-Gunnink et al. (2007) to develop the mathematical modelling framework. This network describes the underlying pathways of chemorepellent gradient sensing in D. discoideum. Working within this modelling framework we address whether the postulated interactions of the pathways and species in this network can lead to a chemorepulsive response. We also analyse the possible role of additional regulatory effects (such as additional receptor regulation of enzymes in this network) and if this is necessary to achieve this behaviour. Thus we have investigated the receptor regulation of important enzymes and feedback effects in the network. This modelling framework generates important insights into and testable predictions regarding the role of key components and feedback loops in regulating chemorepulsive gradient sensing, and what factors might be important for generating a chemorepulsive response; it serves as a first step towards a comprehensive mechanistic understanding of this process. |
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Keywords: | Gradient sensing Chemorepellent Spatial signalling Fugetaxis Negative chemotaxis |
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