Engineering liquid-liquid phase separation for the control of signalling processes

Prof. Dr. Wilfried Weber (CIBSS-PI, CIBSS Speakerteam member), Institute of Biology II (Faculty of Biology), University of Freiburg

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Optogenetic methods enable unprecedented spatiotemporal resolution in the control of cellular signalling reactions. By fusing photoreceptors responsive to red, green, blue and UV light to signalling molecules, we achieve control of molecular signalling reactions in space- and time-resolved and dose-dependent manner. Further, combining multiple photoreceptors within one cell, we can control multiple molecular reactions in a mutually orthogonal manner.

Currently, we are using photoreceptors to control liquid-liquid phase separation of transcription factors and demonstrate that the resulting “transcription factor droplets” correlate with modulated in transgene expression. We are currently expanding this concept on other transcription factors and signalling pathways to control cell fate and function. The precise perturbation of signalling reactions allows us to analyze how signals are propagated across spatiotemporal scales and how multiple signals are integrated with each other. We are collaborating on these projects with Jens Timmer and Bodo Grimbacher.