Scientific Publications
An integrative approach to computational modelling of the gene regulatory network controlling Clostridium botulinum type A1 toxin production
PLOS Computational Biology, 12, e1005205
Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information. In this paper we present modelling based on the integration of diverse information from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Here, we integrate these regulatory elements, together with a population dynamics model to build the first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level as a means of creating opportunities that could be used to manage and control botulism, and potentially contribute to improved methods for the production of toxin used for therapeutics.
PLOS Computational Biology, 12, e1005205
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