# Understanding developmental control of cell polarity using single-cell in vivo biochemistry

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2022 · $371,827

## Abstract

Project Summary / Abstract
Cell polarity is a fundamental feature of eukaryotic cells, and must be coordinated between cells and regulated
to allow for normal animal development and tissue homeostasis. Despite genetic identification of proteins
involved in cell polarity and a large body of knowledge about their interactions in vitro, it remains unclear how
polarity proteins are organized into signaling complexes in cells. This lack of knowledge has prevented the field
from understanding mechanisms of developmental control of polarity signaling in vivo.
The long-term goal of the proposed research is to resolve the network of protein-protein interactions that
supports animal cell polarity and to understand how this network can respond to developmental signals. To
enable progress towards this goal, the applicants have developed innovative experimental tools that allow
single-molecule measurements of native protein complex abundance in single cells. This project focuses on
two evolutionarily conserved protein kinases, called aPKC and PAR-1, that play central roles in polarity by
localizing to opposite ends of a polarized cell and dictating polarized cell behaviors. The applicants will make
use of the C. elegans early embryo, in which cells reproducibly polarize in response to multiple spatial and
temporal cues, to discover mechanistic links between developmental signals and the polarity machinery.
The central hypothesis of this work is that that developmental signals control cell polarity by altering the
molecular complexes in which aPKC and PAR-1 reside. This hypothesis will be explored by identifying
dynamic aPKC and PAR-1 complexes that control polarity (Aim 1); by determining how polarity signaling is
coordinated with cell cycle cues in the zygote (Aim 2); and by determining how developmental cues re-program
polarity signaling in later embryos. The work proposed in this application is significant because it will reveal
fundamental mechanisms controlling cell polarity, and because it places these mechanistic studies in a
developmental context. The proposed work is innovative, in the applicant’s opinion, because it uses novel
experimental methods to perform biochemical, mechanistic studies in vivo. By studying the biochemical control
of aPKC and PAR-1 in multiple cellular and developmental contexts in a single experimental system, this work
will identify fundamental mechanisms of PAR polarity signaling and to learn how these mechanisms are
deployed to achieve different outcomes during development.

## Key facts

- **NIH application ID:** 10455085
- **Project number:** 5R01GM138443-03
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Daniel J Dickinson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $371,827
- **Award type:** 5
- **Project period:** 2020-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455085

## Citation

> US National Institutes of Health, RePORTER application 10455085, Understanding developmental control of cell polarity using single-cell in vivo biochemistry (5R01GM138443-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10455085. Licensed CC0.

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