Magnetogenetics for Drosophila

Abstract

Magnetically sensitive genetically encoded channels enable remote activation of specific neural networks deep within the brain of freely moving animals. Recent progress coupling various TRP channels and the biogenic magnetic nanoparticle ferritin in mammalian cells shows significant promise for creating such “magnetogenetic” technology, but this approach relies on ferritin assembly by endogenously expressed subunits. This reliance on endogenously expressed ferritin subunits makes it difficult to study the efficacy of ferritin formation and iron loading and prevents transfer of the technology developed with mammalian ferritin to species like Drosophila that express divergent ferritin proteins. In addition, magnetogenetics in Drosophila provides two key advantages for optimizing the magnetic sensitivity of the proteins: 1) because Drosophila ferritin is secreted and circulates throughout the animal within hemolymph, the particles can be more easily isolated for characterization, 2) once isolated, we can bind these ferritin nanoparticles to other proteins with minimal reduction of iron loading. By developing magnetogenetic channels for Drosophila with an extracellular binding site for functionalized ferritin or superparamagnetic nanoparticles, we can study the responses of the channels to low frequency magnetic stimulation with fewer unknowns and create driver lines expressing functionalized magnetogenetic ferritin nanoparticles. Drosophila also enable this technology to be rapidly tested in various cell types by taking advantage of large depositories of UAS/Gal4 drosophila lines. We believe developing these magnetogenetic channels and functionalized biogenic magnetic nanoparticles will create a testbed for behavioral studies in drosophila and enable researchers to rapidly test responses to stimuli throughout the animal while gaining a deeper understanding of the physics behind magnetogenetics.