# Structural basis of dynein-driven ciliary motility

> **NIH NIH R35** · YALE UNIVERSITY · 2021 · $410,650

## Abstract

Summary:
 Cilia and flagella are evolutionarily conserved appendage-like organelles that sense the
extracellular environment, drive the movement of individual cells, or transport fluids. Defects of ciliary
functions lead to numerous diseases termed the ciliopathies, which result in a variety of congenital
disorders and cause a broad spectrum of symptoms. The outer-arm dynein (OAD) is a key motor
protein that generates most mechanical forces to power the ciliary beating by ATP hydrolysis. OAD
mutations were found in over half of the primary ciliary dyskinesia (PCD) patients. These mutations
have orthologs in algae and ciliates, which also lead to cilia/flagellar dysfunctions, suggesting that the
lower species and humans have important commonalities on the mechanisms of ciliary motility.
However, lacking an atomic model of most ciliary components has been a main barrier to our
understanding the cilium system. We will use the model systems T. thermophila and C. reinhardtii to
elucidate the cilium assembly and dynein-driven ciliary motility in the following years, with an emphasis
on OAD and its regulation. We aim to reveal the mechanisms in atomic details by a combination of
cryo-EM/ET, correlative light and electron microscopy (CLEM), biochemistry, cell biology, single-
molecule biophysics, and computational modeling etc. Our aims for the following years are to
understand how OAD arrays are formed in cilia, how OADs coordinate with each other during beating,
how the OAD activity is regulated by other ciliary components (such as central pair) and extracellular
signals, and build an atomic model of axoneme. We will co-develop cryo-EM/ET methods to address
long-standing problems. The revealed mechanisms will provide more accurate information for our
future mutagenesis in mammalian systems and human disease models.

## Key facts

- **NIH application ID:** 10276301
- **Project number:** 1R35GM142959-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Kai Jack Zhang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,650
- **Award type:** 1
- **Project period:** 2021-09-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10276301

## Citation

> US National Institutes of Health, RePORTER application 10276301, Structural basis of dynein-driven ciliary motility (1R35GM142959-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10276301. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*