FOR 1279:  “Protein-based Photoswitches” as Optogenetic Tools

• Subject Area: Biology
• Term: from 2010 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 119438981

The goal of the Research Unit is to promote the understanding of light-activated ion channels and enzymes and to provide new and versatile tools for neuroscience and cell biology (optogenetics). We will focus on four protein prototypes: channelrhodopsin (ChR), a photoactivated cyclase (PAC), a blue-light activated transcription factor (Aureochrome) and an azobenzene-coupled light-activated ionotropic glutamate receptor (LiGluR).
These model proteins have exceptional properties that allow modification of very general characteristics of eukaryotic cells with light, namely the membrane potential (depolarising and hyperpolarising), cyclic nucleotide levels and expression of specific genes. For the production and analysis of these proteins we will employ organic chemistry, electrophysiology, genetics, biochemistry, structural biology, spectroscopy, light-evoked animal behaviour and theory.
Based on new structural and functional information and theoretical considerations, the proteins will be tailored with respect to absorption, substrate specificity, kinetics and improved expression in host systems. After quality tests in oocytes, HEK-cells, COS-cells and hippocampal neurons, proteins will be studied in Drosophila, C. elegans or zebrafish, and finally collaboratively in mammalian model systems.

• DFG Programme: Research Units

Projects

• Analysis and engineering of natural photoreceptors to Light-manipulate cyclic nucleotides, Ca2+ and membrane voltage in animal cells (Applicant Nagel, Georg )
• Central Coordination Project (Applicant Hegemann, Peter )
• Channelrhodopsin colour tuning (Applicants Elstner, Marcus ;  Hegemann, Peter )
• Characterization of biomodal light-switchable rhodopsins and tailoring for optogentic application (Applicant Hegemann, Peter )
• Developing and implementing novel light-switches in the nervous system of the nematode (Applicant Gottschalk, Alexander )
• Development of Light-Gated Ion Channels With Red-Shifted Action Spectra (Applicants Elstner, Marcus ;  Trauner, Dirk )
• Light-Regulated Sensor Histidine Kinases - Structure, Dynamics & Optogenetics (Applicant Möglich, Andreas )
• Optogenetic modulation of stress signaling - towards a new animal model for depression (Applicant Ryu, Ph.D., Soojin )
• Signal transduction in LOV and BLUF blue light photoreceptors. (Applicant Schlichting, Ilme )
• Spatio-temporal observation of structural changes in the optogenetic proteins halorhodopsin and YF1 (Applicants Heberle, Joachim ;  Schlesinger, Ramona )

• Spokesperson: Professor Dr. Peter Hegemann