Non-coding RNA in the olfactory system of Drosophila

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Project summary Odor detection and identification are critical to animal survival. Major questions remain about the molecular mechanisms by which olfactory systems are modulated by environmental conditions and the internal state of the animal. Non-coding RNA (ncRNA) remains virtually unexplored in olfaction. Many structural and functional features of ncRNA could be exploited in olfactory coding and modulation, and a rapidly expanding body of evidence shows that ncRNA plays a profound role in other neural systems. Drosophila is a powerful model organism in which to investigate the potential role of ncRNA in the molecular basis of odor perception. This proposal concerns ncRNA in the Drosophila antenna, with a focus on one particularly intriguing ncRNA. In preliminary work, I characterized the antennal ncRNA landscape of D. melanogaster and identified 10 abundant ncRNAs that are enriched in the fly antenna, including 4 that are enriched in food- and/or pheromone-sensing sensilla. I found that one of these ncRNAs is upregulated when the animals are starved and I named it ANRUS, Antennal ncRNA Upregulated by Starvation. The proposed project is designed to characterize these antennal ncRNAs, with a focus on ANRUS. The first aim is to determine the expression pattern of ANRUS. I will perform single molecule fluorescence in situ hybridization to determine in which cells and cellular compartments this ncRNA is localized, which may give clues to its function. If detected in neurons, I will identify the neuronal class in which the ncRNA is expressed. The results may suggest that an ncRNA acts in the response to certain odors. Dynamics of ANRUS localization will be assessed across certain conditions (e.g. starvation, pre-exposure to odorant, isolation and age). Changes in subcellular localization may indicate a role in adaptation to the corresponding environmental or internal state. The second aim is to characterize flies lacking ANRUS. I have generated mutant flies lacking ANRUS, and preliminary electrophysiological measurements revealed that in flies lacking ANRUS, certain neurons fail to increase their olfactory sensitivity under starvation. I will further examine the mutant flies in electrophysiological and behavioral assays to test the hypothesis that this ncRNA plays an essential role in olfactory modulation and coding in starved flies. The overarching goal of this project is to broaden our understanding of the molecular basis of olfaction. Ultimately, this project could reveal new principles of sensory coding and new roles of ncRNAs.