# Molecular Mechanisms of Connecting Cilium Function in the Vertebrate Eye

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $460,148

## Abstract

Project Summary
The long-term goal of this project is to improve our understanding of the molecular mechanisms of inherited
retinal diseases (IRDs) and to develop personalized treatments. Strikingly, ciliopathies have been identified
as one of the major causes of IRDs with 25% of the known disease-causing genes involved in proper cilia
formation and function in photoreceptor cells. However, despite the large number of retinal disease genes
related to cilium function, the precise disease mechanisms remain largely unknown. We have recently
discovered a novel subdomain of the photoreceptor connecting cilium (CC), named the photoreceptor-
specific transition zone (PSTZ), which plays a critical role in CC stability and function. Establishment of the
PSTZ depends on Spata7, a known LCA disease gene, and other members of the RPGR complex. In this
proposal, we plan to utilize Spata7 as an entry point to better understand the function of this novel structure
in the connecting cilium of photoreceptor cells. Our Specific Aims are to:
Specific Aim 1: Investigate the mechanism of PSTZ establishment
Specific Aim 2: Determine the role of RPGR complex members in PSTZ structure and function
Specific Aim 3: Determine the role of Spata7 in RPGR complex assembly and in
 establishment versus maintenance of CC structure and function
Together these studies will provide a systematic evaluation of the PSTZ structure, key protein composition,
regulation, and function, thereby providing novel insights concerning the molecular mechanisms of protein
trafficking through the connecting cilium of photoreceptor cells. Given the central role primary cilia play not
only in retinal disease, but also many other syndromic pathologies, these aims have the potential to make a
high impact in our understanding of and ability to diagnose and treat human disease.

## Key facts

- **NIH application ID:** 10172910
- **Project number:** 5R01EY028970-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Graeme Mardon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $460,148
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172910

## Citation

> US National Institutes of Health, RePORTER application 10172910, Molecular Mechanisms of Connecting Cilium Function in the Vertebrate Eye (5R01EY028970-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10172910. Licensed CC0.

---

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