The role of sensory cilia architecture in shaping chemosensory neuron responses

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Project summary Animals must detect environmental chemicals in order to locate food sources, recognize predators, and identify mates. Molecules necessary for odorant detection are housed within the cilia of olfactory sensory neurons. Defects in olfactory cilia structure, or the trafficking and localization of sensory molecules, result in anosmia, suggesting that understanding the biology of these processes is highly relevant to human health. Cilia structures range in complexity, and these morphologies dictate protein composition and the organization of signaling molecules within them. Cilia structure can also be further modified by the environment, but the molecular mechanisms driving these alterations remain unclear. Although cilia morphology is thought to be a critical determinant for shaping sensory responses, the role of cilia architecture in sensory signal transduction, and in particular for responses to olfactory cues, is poorly understood. The C. elegans sensory nervous system is an ideal model in which to address these questions. Individual chemosensory neurons in C. elegans exhibit diverse cilia morphologies, and each neuron type responds to a defined set of chemicals to drive attraction or aversion behaviors. As in other organisms, C. elegans cilia house all olfactory receptors and signaling molecules. Moreover, a subset of olfactory neuron cilia can be remodeled by sensory activity. These features, combined with its genetic tractability and amenability to in vivo imaging, provide a unique opportunity to elucidate key mechanisms responsible for shaping cilia morphology and function. This proposal will systematically explore how specialized cilia morphologies contribute to the unique response profiles of individual chemosensory neurons in C. elegans, and will identify the cellular and molecular mechanisms by which these cilia morphologies are further modified by sensory activity. This work will provide a framework for understanding the pathogenesis of cilia-related defects in chemosensory signaling. The experiments described in this proposal will provide me with valuable training in high-resolution microscopy, high-resolution quantitative analyses of chemosensory behaviors, and quantitative analyses of neuronal function via in vivo calcium imaging. Further, my proposal includes concrete plans to enhance my training in mentorship, networking, and scientific communication, areas that are critical for my goal to become an independent researcher.