PhD position on targeted scintillator nanoparticles for X-ray-mediated optogenetics in behaving mice (P2207)

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Join our interdisciplinary team of chemists, neurobiologists and X-ray physicists to work on the next generation of wireless, minimally invasive X-ray mediated optogenetic tools.

Manipulating the activity of well-defined groups of neurons is an important tool for probing the function and connectivity of neuronal circuits [1,2]. In optogenetics, light-switchable transmembrane proteins are expressed in specific groups of neurons which can be depolarized (excited) or hyperpolarized (inhibited) by visible light with high temporal precision [3]. But the penetration depth of visible light is limited to a few hundreds of micrometres from the brain surface [4]. Conventional optogenetics requires an invasive surgery to implant tethered optical fibres that are relatively thick and increase the risk of brain tissue damage and neuroinflammation. Therefore, X-ray mediated optogenetic manipulation has been proposed as a minimal invasive alternative [5]. We aim to develop functionalized and biocompatible scintillator nanoparticles (SNPs) that can adhere to cell membrane-localised light-switchable proteins in neurons. If exposed to X-ray radiation, these SNPs will emit visible light which activates the light-switchable proteins. This project is part of a larger interdisciplinary effort at the PSI with the goal of developing a pipeline for low-dose focal X-ray mediated optogenetics and in vivo two-photon calcium imaging in behaving mice. Biocompatible, functionalized scintillator nanoparticles could become a very interesting non-invasive alternative for optogenetic therapies of neurological diseases in humans.