# Maintenance and Disassembly of Olfactory Cilia

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $481,988

## Abstract

TITLE: Maintenance and Disassembly of Olfactory Cilia
The long-term goal of this project is to determine the role of cilia in the regulation and maintenance of olfactory
function and their alterations in cilia-related disorders. Olfactory dysfunction is common, affecting at least 16
million people in the U.S. alone. Our lab and others have found olfactory dysfunction to be a clinical manifestation
of a class of human genetic disorders termed ciliopathies. Bardet-Biedl syndrome (BBS) is one such disorder, in
which the altered cilia morphology of olfactory sensory neurons (OSNs) renders the cells unresponsive to odors.
Despite the identification of numerous genes underlying ciliopathies, curative therapies (including for olfactory
dysfunctions) are not yet available to patients. We reported that gene replacement to restore cilia and hence
sensory input in a limited number of differentiated OSNs was sufficient to rescue peripheral odor responses in
mouse models of a subset of ciliopathies. However, to better understand cilia biology in the olfactory system and
advance potential therapies, we must define the cellular mechanisms underlying olfactory penetrance of
ciliopathies. We must also determine whether these mechanisms are conserved across different ciliopathies
and might thus be amenable to the same therapeutic strategies. OSN cilia compartmentalize all of necessary
signaling machinery for odor detection and even though OSN cilia can be lost in both physiological and
pathological conditions, the cellular mechanisms that maintain the integrity of this essential OSN cell
compartment remain poorly understood. Cilia in other cells and organisms contain a multiprotein complex at its
base, termed the transition zone (TZ), that functions as a regulatory gate to control the unique protein and lipid
composition of cilia. Surprisingly little is known about the TZ in OSNs. This grant application will elucidate the
composition and subcellular organization of the OSN cilia TZ and how aberrant protein and lipid translocation
into cilia contributes to the disassembly of cilia. Our preliminary data suggest that alterations in intracellular
Ca2+ contribute to cilia disassembly by disrupting TZ components. We hypothesize that sustained elevations of
intracellular Ca2+ result in TZ remodeling of OSN cilia that is permissive for changes in cilia membrane lipid
distribution and actin infiltration, both of which are necessary for cilia disassembly in ciliopathies. Therefore,
we propose the following Specific Aims: (1) Determine the composition and organization of the OSN cilia TZ and
alterations accompanying disassembly in ciliopathies; (2) Determine the effects of elevated intracellular Ca2+ on
OSN cilia disassembly; (3) Determine the role of membrane PIP2 redistribution and F-actin infiltration in cellular
mechanisms of OSN cilia disassembly. Successful completion of this work will provide critical new insights
into the pathogenesis of human sensory perception dise...

## Key facts

- **NIH application ID:** 10348789
- **Project number:** 5R01DC019345-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Jeffrey Martens
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $481,988
- **Award type:** 5
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348789

## Citation

> US National Institutes of Health, RePORTER application 10348789, Maintenance and Disassembly of Olfactory Cilia (5R01DC019345-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10348789. Licensed CC0.

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