Oscillations in Gene Regulatory Networks: The Importance of Spatial Aspects

Dr Cicely Macnamara (University of Glasgow)

Thursday 25th November, 2021 14:00-15:00 Room 110/ ZOOM (ID: 939 7280 8469)

Abstract

Transcription factors typically exert control over molecular levels through feedback mechanisms - proteins bind to promoters in the nucleus and either up-regulate or down-regulate production of mRNA. Many gene regulatory networks (GRNs) contain negative feedback loops whereby promoter binding by proteins reduces the transcription rate of a gene. This can be either direct and self-repressing if the promoter binding affects the protein's own gene, or indirect if the effect is on a subsequent gene in a given network. Typically, negative feedback leads to mRNA and protein levels oscillating over time but also spatially since the molecules must move between the nucleus and cytoplasm. In the models presented in this talk I shall focus on capturing this oscillatory spatio-temporal behaviour. Firstly, a PDE model of the Hes1 system is proposed in order to investigate the importance of spatial aspects, specifically diffusion and the location of gene and protein production sites. The model may be easily extended to examine spatio-temporal models of synthetic GRNs e.g. n-gene repressilators and activator-repressor systems and these will be discussed. Finally, a stochastic spatio-temporal model is formulated since such a model connects more accurately with both the underlying biology (by incorporating promoter binding) and experimental data (such systems are observed to be noisy and in many cases the actual numbers of molecules involved are quite low).

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