Dynamics of toxin-antitoxin stress response networks: an interdisciplinarycomputational and in-vivo approach.

Mathematical modeling is key for understanding the properties of dynamic processes in science and engineering. It allows transition from a descriptive approach to science and engineering to a predictive stage, where accurate predictions from models are compared to observations and/or experimental results. In biological systems, this step is particularly challenging. In living cells, highly complex networks of interacting genes/proteins operate under non-equilibrium conditions. Understanding how a cell operates and stays alive is equivalent to understanding these molecular networks and their dynamical behavior.
The genomes of bacteria and archaea contain small operons encoding a "toxin" and its corresponding neutralizing "antitoxin". These gene pairs form a so-called toxin-antitoxin (TA) module of which the physiological function is heavily debated. We propose TA modules as model systems to study gene regulation and its integration with other levels of regulation at the translation and post-translational level. For this we will use a combined experimental and computational approach. The outcome of these studies should provide direct insights into the most likely physiological role of three distinct families of TA modules and how the regulatory mechanisms present at different levels (transcription, translation, activity) interact. In addition, it will provide valuable information on whether TA activation would be a suitable target for the development of antibacterial drugs.