Second generation genetically encoded photosensitizers and killers for systems neuroscience

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New developments of optogenetic reagents are constantly transforming neuroscience until today. In the course of this process, tools have been engineered that aim at efficient photo-ablation of cells in vivo. Some of these reagents demonstrated usefulness for certain applications in vivo. However, it appears that optogenetic ablation of cells with the aid of genetically encoded chromophores has not yet become a versatile tool in circuit neuroscience and that the method requires improvement to realize its full potential. We here propose a collaborative effort that aims at engineering highly sensitive second generation optogenetic tools for the reliable photo-ablation of genetically targeted cells in vivo. Building on two families of proteins that produce reactive oxygen species (ROS) upon illumination, the labs of Griesbeck and Reiff propose to join forces for the engineering (Griesbeck) and in vivo application/verification (Reiff) of new ROS-producing proteins with improved properties. Candidates will be quantitatively tested in physiological and behavioral experiments in Drosophila melanogaster in vivo. Thereby, we will focus on experiments on visual processing including the processing of optic flow, the visual control of navigation and neuronal computations underlying color vision. Improved proteins should include powerful features of classical optogenetic reagents like activation with high spatial resolution and cellular specificity, should as work on the subcellular level to probe the roles of spines or synapses within a circuit, and be largely orthogonal to existing optogenetic reporters. Thus, new ROS-generating proteins for light-induced ablation may become highly useful for neuroscience research in genetic model organisms, but also for a number of other applications in biology and biomedicine.