# Intracellular pattern formation

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2024 · $302,000

## Abstract

PROJECT SUMMARY/ABSTRACT
We will investigate how cytoskeletal organelles organize into patterns in the cell. The fields of motile cilia
in epithelial cells and the rows of stereocilia in the inner hair cells are examples of physiologically-
important organelle patterns. The known pathways do not satisfactorily explain how organelle patterns
form. The ciliated protists (ciliates) assemble unusually complex surface (cortical) patterns. Ciliates
faithfully duplicate their cortical pattern during cell division and, despite its complexity, the cortical pattern
remains nearly invariable in a population. Thus, even subtle deviations from the normal pattern (e.g. due
to a mutation or trauma) can be detected and analyzed over many generations. In the genetic model
ciliate Tetrahymena thermophila, hundreds of cortical organelles, including cilia, are arranged along the
anteroposterior and circumferential (left-right) axes. We recently identified causal mutations in several
classical Tetrahymena pattern mutants, in which organelles assemble at incorrect positions. We found
that orthologs of the Hippo pathway kinases and cyclin E are critical for patterning on the anteroposterior
axis. We identified a strong candidate for Hpo1, a protein that regulates the positions of organelles on
the cell’s circumferential axis. The molecular activities through which these pattern-regulating proteins
act, and the basis of their restricted cortical localizations, remain unknown. We will explore the molecular
composition of the pathways that drive pattern formation in Tetrahymena, study the properties of the
pattern-regulating proteins and develop genetic and biochemical screens to systematically unravel the
principles of intracellular patterning through unbiased approaches. The overarching goal for Aim 1 is to
uncover the molecular circuitry of “early” Hippo signaling that controls the initial positions of organelles
that form during cell division on the anteroposterior cell axis in Tetrahymena. Aim 2 will investigate how
the “late” Hippo signaling circuit and cyclin E interact (in a mutually antagonistic manner) to induce and
maintain cortical structures that form at the division plane. Aim 3 will investigate factors that regulate the
circumferential pattern, including Hpo1, a protein that localizes to the right side of the cell.

## Key facts

- **NIH application ID:** 10813158
- **Project number:** 5R01GM135444-04
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** JACEK GAERTIG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $302,000
- **Award type:** 5
- **Project period:** 2021-05-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813158

## Citation

> US National Institutes of Health, RePORTER application 10813158, Intracellular pattern formation (5R01GM135444-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10813158. Licensed CC0.

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