Cluster of Excellence –
University of Freiburg

Remote control of cell signaling

Chemically responsive synthetic regulators to control gene expression

Based on microbial genetic regulators such as small molecule-responsive repressor proteins we designed synthetic molecular tools to control the expression of transgenes in mammalian cells. Using this approach we developed mutually compatible gene switches responsive to different inducers such as macrolide antibiotics, quorum-sensing messengers, amino acids, volatile aldehydes or vitamins. We applied these molecular switches to construct synthetic biological networks to dynamically control gene expression programs in mammalian cells or to discover new compounds that specifically suppress antibiotic resistance in Mycobacterium tuberculosis. These compounds were the basis for the establishment of the preclinical stage company BioVersys (www.bioversys.com).

 

Optically responsive synthetic regulators to control cell signalling

In addition to the above-described chemically responsive synthetic regulators and molecular tools we engineered microbial and plant photoreceptors to achieve optical control of signaling processes in mammalian cells and zebrafish. For example, we published the first red and UV light-responsive gene switch in mammalian cells that was combined with blue light-responsive promoters to achieve independent expression control of three different genes within one single cell by simple illumination with red, blue or UV light. In addition, members of our group published the first light-regulated protein kinase in mammalian cells or a molecular tool for shuttling proteins between the nucleus and the cytoplasm in response to illumination with red and far-red light, respectively.