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.