Microbial cells have evolved various ways in which they respond to changes in environmental conditions - frequently causing the adjustment of gene expression patterns. One focus of our research is to reverse-engineer the molecular mechanisms behind such natural gene regulation strategies and to provide model-driven hypotheses for the evolutionary consequences associated with them. For instance, by using a combination of theoretical and experimental methods we decipher some of the regulatory mechanisms behind stochastic phenomena in the expression of carbon utilization systems in Escherichia coli and study the dynamics and interconnections of cell envelope stress response systems in Bacillus subtilis.
In addition to our reverse-engineering efforts, our second major research focus is the forward design and implementation of small, well-defined synthetic circuits with novel functionalities. Based on the quantitative experimental characteristics of individual biological parts, we perform in silico simulations to explore the signal processing potential of those circuit modules. In doing so, our analysis serves as a theoretical guide for the optimal design of synthetic gene regulation strategies, which can ultimately be applied, for instance, to drive the heterologous expression of biosynthetic pathways. However, the success of implementing new functionalities into microbes is challenged by the inherent interconnectivity of virtually any compound within a living cell. Therefore, a central goal of our work is to better understand the context-dependence of synthetic biology building blocks. On a more general level, this will enable us to infer some of the design rules of bacterial gene regulation, which will be applied to construct “orthogonal”, i.e., context-independent, regulatory circuits.