SYNTHETIC ECFDEVICES · Extracytoplasmic Function (ECF) Sigma Factors: From Regulatory Specificity to Synthetic Switches

Bacillus subtilis is a model organism for basic and applied research that has been intensively studied for more than two decades in the course of EU-funded research consortia and – with the FP7-project BaSynthec – has recently entered the age of Synthetic Biology (SynBio). This emerging interdisciplinary research area has a huge potential for biotechnological applications and is a major focus of upcoming EU-funded research initiatives, as reflected by the first transnational ERASynBio call this year and the focus of the EU-program Horizon 2020 on innovation and biotechnology. Based on the comprehensive knowledge of B. subtilis biology, its potential as an important chassis for future SynBio applications is unquestioned. But the lack of standardized tools for designing and implementing in vivo expression programs for metabolic engineering currently limits its use. It is the aim of this project to contribute to such a genetic toolbox by exploiting the enormous potential of Extracytoplasmic Function σ factors (ECFs). These transcriptional regulators provide a huge reservoir for developing SynBio switches. But since their diversity, specificity and ubiquitous distribution has only recently been discovered by the host group, ECFs have so far not been used for SynBio purposes. Using the comprehensive knowledge of the host group on B. subtilis genetics, ECF biology, and SynBio rationales, this project aims at developing innovative orthogonal ECF-based switches and devices for controlling complex expression programs in B. subtilis, based on novel actinobacterial ECF groups. The success of this project, set at the interface between basic molecular research and SynBio application, furthermore builds on the applicant’s strong expertise in bacterial genetics, the superb infrastructure of the research environment at the LMU Biocenter, and the support provided to the applicant by the host institution.