# Regulation of Lens Fiber Cell Structure and Function by Post Translational Modification of Intermediate Filaments

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $392,500

## Abstract

Project Summary/Abstract
The ocular lens is an excellent model in which to study cellular and molecular aging. The lens is
arranged as a series of concentric shells each 1 fiber cell thick. Lenses grow throughout life by
addition of new shells to existing shells. Because no cells are lost with age, the shells are
arranged in exact chronological order by birthdate, with the oldest at the center, and youngest at
the surface. In humans this is about 2,500 concentric shells. Even more remarkable, fiber cells
retain all their membranous organelles only until they complete formation of a new shell, at
which point they are destroyed. In human lenses, only the outer 100 or so of the 2,500 layers
has organelles. The other 2,400 layers are incapable of protein synthesis, and live the lifetime of
the organism without protein replacement. Despite the inability to synthesize new protein, fiber
cells undergo dramatic structural changes well past the point at which they have lost organelles.
On the basis of preliminary data, and previously published work, we hypothesize that these
structural changes are powered by a progression of post translational modifications (PTMs) to
lens-specific intermediate filament (IF) proteins. We hypothesize that these PTMs change
protein function which then orchestrates structural change. The field of lens biology is revealing
a large number of similar processes that progress in cells lacking biosynthetic potential. We
believe this proposal can directly test the cause (PTM) and effect (structural change) for at least
one set of these changes, and do so with cell‐level resolution. Successful completion of this
proposal will establish a mechanism by which cells can effect a progression of predictable
structural changes, over time, in the absence of protein synthesis. To do this, we will identify
PTMs, localize them with respect to structural change, then test the effect of the PTM directly by
using CRISPR to genetically modify zebrafish IF PTM sites, and then translate key observation
from zebrafish, into a mouse model.

## Key facts

- **NIH application ID:** 9900012
- **Project number:** 5R01EY027430-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** PAUL Gillespie FITZGERALD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900012

## Citation

> US National Institutes of Health, RePORTER application 9900012, Regulation of Lens Fiber Cell Structure and Function by Post Translational Modification of Intermediate Filaments (5R01EY027430-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9900012. Licensed CC0.

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