Multi-chromatic control of mammalian gene expression and signaling

26.04.2013

Müller K, Engesser R, Schulz S, Steinberg T, Tomakidi P, Weber CC, Ulm R, Timmer J, Zurbriggen MD, Weber W.

Nucleic Acids Res. 2013;41(12):e124

Nucleic Acids Res.        online article

The emergence and future of mammalian synthetic biology depends on technologies for orchestrating and custom tailoring complementary gene expression and signaling processes in a predictable manner. Here we demonstrate for the first time multichromatic expression control in mammalian cells by differentially inducing up to three genes in a single cell culture in response to light of different wavelengths. To this end, we developed an ultraviolet B (UVB)-inducible expression system by designing a UVB-responsive split transcription factor based on the Arabidopsis thaliana UVB receptor UVR8 and the WD40 domain of COP1. The system allowed high (up to 800-fold) UVB-induced gene expression in human, monkey, hamster and mouse cells. Based on a quantitative model we determined critical system parameters. By combining this UVB-responsive system with blue and red light-inducible gene control technology we demonstrate multichromatic multi-gene control by differentially expressing three genes in a single cell culture in mammalian cells and we apply this system for the multichromatic control of angiogenic signaling processes. This portfolio of optogenetic tools enables the design and implementation of synthetic biological networks showing unmatched spatiotemporal precision for future research and biomedical applications.