Modelling of the GAL1 Genetic Circuit in Yeast Using Three Equations

Abstract

Synthetic gene circuits can be used to modify and control existing biological processes and thus e.g. increase drug yields. Currently their use is hampered by the, largely, trial and error approach used to design them. Lack of reliable quantitative dynamical models of genetic circuits e.g. prevents the use of well established control design methods. We aim toward creation of a pipeline for automated closed-loop identification of dynamic models of synthetically engineered genetic circuits in microorganisms. As a step towards this aim, we here study modelling of the input-output behaviour of the yGIL337 strain of S. cerevisiae. In this strain expression of the fluorescent reporter can be turned on by growing the yeast in galactose and off by glucose. We perform parameter estimation on a system of three ordinary differential equations of Michaelis-Menten type based on in vivo data from a microfluidic experiment by Fiore et al. (2013) after redoing the data preprocessing. The parameter estimation is done using AMIGO2–a state of the art Matlab toolbox for iterative identification of dynamical models. We show that the goodness-of-fit of our model is comparable to the five models proposed by Fiore et al. and we hypothesise that the system is an adaptive feedback system.