Speaker
Description
Gene regulatory networks (GRNs) underpin many of the most important processes in cellular biology – including cell fate, patterning and adaptation. Whilst the biological realism of GRN models has improved in recent years, there has been little consideration of cell cycle effects on the dynamics of these models. For the classic, bistable toggle switch, we find that the inclusion of cell growth and division can significantly alter the basins of attraction of the two stable states in the model as a result of a shift in the separatrix that divides those basins in the phase plane. Given the highly non-linear nature of the original toggle switch model, we formulate a Boolean modelling framework which allows us to derive analytical expressions for the separatrices in an approximate Boolean model, both with and without division. These expressions allow us to describe "regions of disagreement" in the phase plane in which attraction to the opposite steady state ensues when the cell cycle is incorporated into the Boolean toggle switch. Furthermore, we assess the discrepancies between these regions in the original toggle switch model and our Boolean approximation in dependence of system parameters such as synthesis rates and Hill exponents.
