Dr. Georg Fritz
Quantitative and Computational Microbiology, LOEWE-Zentrum für Synthetische Mikrobiologie, Hans-Meerwein-Straße 6, 35032 Marburg, Germany
Title: Engineering orthogonal synthetic timer circuits in bacteria
The rational design of synthetic circuits is often restricted by cross-reactions between circuit components and physiological processes within the heterologous host. In our work seek to overcome these restrictions by using extracytoplasmic function σ factors (ECFs), which represent ideal orthogonal regulators because of their high promoter specificity. After evaluating several heterologous ECF switches in E. coli and B. subtilis, computational modelling allows us to predict cascades with multiple ECFs. These "autonomous timer circuits" activate a series of target genes with defined time delays, which we find in excellent agreement with experimental data. Our results not only serve as a proof of concept for the application of ECFs as organism-independent building blocks in synthetic biology, but could also be used in biotechnological applications, e.g. to introduce a timing hierarchy in the expression of biosynthetic pathway components.