Use of optogenetics to understand cell-signaling events

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Samuel Juillot, Hannes Beyer, Matias Zurbringgen, Wilfried Weber

BIOSS Centre for Biological Signalling Studies, Germany

Signaling processes are at the heart of cellular responses to environmental cues. Thanks to a precisely controlled exchange of signals between nucleic acids, proteins, organelles and cells, many mechanisms of living cells are perfectly regulated, like the metabolic machinery, cell growth, differentiation, death and the survival in a dynamic environment. Thus, deregulations of signaling pathways result in emergence of diseases like cancer, immunological disorders or metabolic diseases. Most of cell-signaling events are composed into three parts: first there is (i) the reception of an external signal, then (ii) the recruitment of proteins at the plasma membrane in order to allow transduction of the signal and finally (iii) the nuclear translocation of transcription factors. In this work, we designed synthetics modules based on optogenetics to understand cell-signaling processes. Light is an ideal tool to gain spatiotemporal control of biological processes. We used genetically engineered phytochromes, which are plant photoreceptors that naturally convert the information contained in light into biological signal. This family of chromoproteins is particularly attractive for biological applications because these proteins sense and respond to changes in the red-light (660 nm) and far-red-light (740 nm) that are well tolerated by biological systems and that have good tissue penetrance. Phytochrome B (phyB) from Arabidopsis thaliana is one of the best characterized members of this family and is known to interact with its Phytochrome Interacting Factor 3 (PIF3). Based on these two proteins, we designed different systems that control signaling events into mammalian cells with red/far-red-light activation. These cell-signaling events can be controlled in each step of the process at high spatial and temporal resolution.