# Dissecting alternate modes and regulation of ciliary motility

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $457,934

## Abstract

PROJECT SUMMARY
The overall goal of this research is to increase our understanding of how cilia beat by dissecting the molecular
mechanisms and regulation of ciliary motility on a molecular level. Cilia and flagella are conserved and ubiquitous
microtubule-based organelles with important roles in cell locomotion, fluid transport, sensation, cell signaling and
development, which are critical processes for the survival and proper function of many eukaryotic cells and
tissues. In humans, defects in the motility and assembly of cilia are responsible for numerous congenital
diseases, such as primary ciliary dyskinesia, chronic respiratory disease, impaired fertility, brain developmental
defects, congenital heart disease and randomization of the left-right body axis. Cilia motility is driven by the
coordinated activities of thousands of dynein molecules, comprised of multiple isoforms. Our previous studies of
wild type and mutant cilia, and actively beating cilia have opened a new window into the functional organization
of motile cilia. However, long-standing fundamental questions remain about how regulatory signals change
dynein’s activity on a molecular level, what are the roles of the different regulatory complexes during ciliary
motility, and how dyneins are spatially and temporally coordinated to generate the oscillatory beating typical for
cilia. Building on a strong premise of both published and preliminary new data, this proposal directly addresses
these critical gaps through three specific aims that are directed at (Aim 1) revealing mechanisms by which
dynein’s action is regulated to initiate and propagate ciliary waves, (Aim 2) determine the patterns of dynein
activity that generate different ciliary waveforms, and (Aim 3) characterizing ciliary components that assemble
only on specific doublets to ask if their inherently asymmetric distribution contributes to producing ciliary beating.
We use a powerful and innovative combination of modern approaches that include cryo-electron tomography to
image mutant cilia and tagged proteins with molecular resolution, genetics and proteomics, an alternate model
organism to study cilia, and a state-of-the-art “cutting” technique to look “deeper inside” cells than previously
possible. We expect that our combined studies will provide important new conceptual and mechanistic insights
into ciliary motility and regulation, which will also impact our understanding of ciliary diseases.

## Key facts

- **NIH application ID:** 9903364
- **Project number:** 5R01GM083122-11
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Daniela Nicastro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $457,934
- **Award type:** 5
- **Project period:** 2007-09-28 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903364

## Citation

> US National Institutes of Health, RePORTER application 9903364, Dissecting alternate modes and regulation of ciliary motility (5R01GM083122-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9903364. Licensed CC0.

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