# Characterizing three-dimensional structures at the base of primary and motile cilia using cryo-electron tomography

> **NIH NIH F32** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $2,500

## Abstract

ABSTRACT
Cilia are nearly ubiquitous among eukaryotic cells and regulate important processes including motility, sensing,
and signaling. In humans, both motile and immotile (primary) cilia are critical for development and homeostasis,
with disruptions in ciliary function leading to a group of diseases known as ciliopathies. While the three-
dimensional structure of the axoneme of motile cilia has been well-characterized, the molecular structures of
primary cilia, as well as those that comprise the base of cilia (the basal body and transition zone) remain poorly
understood. Taking aim at these gaps, I will use innovative approaches, including cryo-correlative light and
electron microscopy, cryo-focused ion beam milling, cryo-electron tomography, and subtomogram averaging to
generate high-resolution structures of primary cilia from mouse embryonic fibroblasts and the basal
body/transition zone from Chlamydomonas cells. Furthermore, I will characterize the location, structure and
molecular interactions of the transition zone protein Nephrocystin-4 (NPHP4), which helps regulate molecular
trafficking into and out of the cilium and causes human ciliopathies when mutated. Specifically, I will visualize
and compare ciliary structures from wild type and nphp4-null Chlamydomonas and precisely analyze the size
and location of nphp4-mutant structural defects. This research will further our understanding of the three-
dimensional architecture and function of cilia and reveal structural changes underlying ciliary disease
mechanisms.

## Key facts

- **NIH application ID:** 10583292
- **Project number:** 3F32GM137470-02S1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Justine Marie Pinskey
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,500
- **Award type:** 3
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10583292

## Citation

> US National Institutes of Health, RePORTER application 10583292, Characterizing three-dimensional structures at the base of primary and motile cilia using cryo-electron tomography (3F32GM137470-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10583292. Licensed CC0.

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