Nathan Braniff | Applied Math, University of Waterloo
Calibrating Dynamic Gene Expression Models with Respect to Growth-Dependent Cell Physiology
Previous efforts to characterize synthetic gene circuits have largely ignored the effect of strain and growth conditions on circuit dynamics, obfuscating intrinsic parameters of the synthetic circuit with context effects. Here I propose to synthesize available information on E. coli physiology into a model able to predict the effects of growth rate and physiological changes on transcription and translation rates within a given strain. I will use this model to design optimal dynamic perturbation experiments using an optimal control algorithm. This approach can more accurately recover the parameters governing heterologous gene expression and also separate them from physiological variables and growth context. These could be used to predict genetic circuit behavior across strain and growth conditions as well as to better quantify host-circuit interactions.