# Flagellar Motility and Assembly

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $664,076

## Abstract

Cilia and flagella are essentially identical cell organelles that have important roles in human health; as a result,
defects in ciliary proteins cause human diseases, termed “ciliopathies.” The long-term goals of this research
are to understand the structure, assembly, and function of these organelles. The studies will utilize
Chlamydomonas and mice as model organisms, and will concentrate on processes and proteins that are highly
conserved among ciliated organisms. A combination of genetic, biochemical, and cell biological approaches
will be taken. Investigations will focus on three related areas of particular importance for understanding the
basic biology of cilia and ciliopathies. First, experiments will determine the functions and specific locations
within the cilium of uncharacterized ciliary proteins. The cilium contains over 650 proteins, of which fewer than
half have been well characterized. The central pair of axonemal microtubules is apt to be particularly rich in
uncharacterized proteins, so initial efforts will examine it. A second focus will be on the fundamental
mechanism of intraflagellar transport (IFT), which is the movement of large, multi-subunit “trains” from the base
of the cilium to the ciliary tip and then back to the cell body. These trains are made up of complexes including
IFT-A and IFT-B, which carry cargos necessary for the assembly and maintenance of the cilium. Train
formation in the cell body involves recruitment of IFT-A and IFT-B to the base of the cilium, loading of cargo
onto the complexes, attachment of motors to the complexes, and injection of the completed train into the
cilium. When this process is defective, ciliary assembly fails, but little is known about the individual steps in
this process. Studies will use high-resolution structured-illumination microscopy and mutants in which train
formation is arrested at various steps to determine the order of these steps and the roles of individual proteins
in key parts of the process. Related studies will explore the specific function of IFT-A in ciliary assembly. In
addition, single-particle cryo-electron microscopy will be carried out to determine the structure of IFT-A and
IFT-B, which will be important for understanding how these complexes are arranged in the trains. A third focus
will be on the transition zone, a specialized region between the basal body and the ciliary axoneme. The
transition zone acts as a barrier that, in concert with IFT, is important for establishing and maintaining the
protein content of cilia. However, the transition zone is still largely a “black box.” Mutants with defects in
transition zone proteins will be investigated to learn more about the specific roles of these proteins in transition
zone function and assembly, and to determine the composition of the highly conserved Y-links, which connect
the transition zone microtubules to the overlying membrane and are critical to the transition zone's barrier
function. The results will fill...

## Key facts

- **NIH application ID:** 9923718
- **Project number:** 5R35GM122574-04
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** George B Witman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $664,076
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923718

## Citation

> US National Institutes of Health, RePORTER application 9923718, Flagellar Motility and Assembly (5R35GM122574-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9923718. Licensed CC0.

---

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