UBC Math Bio Seminar: Jalal Khouhak

Cell-free protein synthesis systems (CFPSS) constitute a powerful tool to study translation dynamics. We consider two different eukaryotic CFPSS (extracted from Rabbit Reticulocyte and Plasmodium Falciparum lysates), and compare how their translation dynamics is regulated, by performing a series of experiments measuring time series of protein level, after adding mRNA at different concentrations and pre-incubation times. The two systems produce different dynamics, which we quantify and interpret as the result of differences in reactions. In the Rabbit system, translation reaction establishes quickly, but the system is sensitive to a translation-independent degradation of resources. In contrast, in the P. Falciparum system, a significant delay for initiating translation is observed, while we did not find any significant impact of the pre-incubation time. We further introduce a system of differential equations to mathematically model the translation dynamics, as a function of the mRNA concentration and available resources, according to these observations. Upon fitting the model parameters to the experimental data, our model successfully captures the dynamics of both systems, with a significant difference in the transition rate from inactive to active mRNA between Rabbit and P. Falciparum. Overall, our study highlights the existence of different factors that can impact the dynamics and limit translation across eukaryotic CFPSS, with more experiments needed in the future to exactly identify them.