# Molecular mechanisms underlying the establishment of cell polarity.

> **NIH NIH R35** · AUGUSTA UNIVERSITY · 2023 · $11,305

## Abstract

Project Summary (parent grant): R35GM145340
A fundamental feature of eukaryotic life is the establishment and maintenance of cellular
polarity. Molecular motors help to establish polarity by transporting mRNAs, proteins, vesicles,
and organelles to specific sites within the cell. A variety of organisms from the single-celled
yeast to humans use mRNA localization coupled with translational regulation as a way to
asymmetrically sort proteins. The prevalence of this phenomenon is best illustrated in
developing embryos, neurons and epithelial, in which thousands of mRNAs are spatially
localized. When this process is compromised, it can result in developmental and neurological
disorders. Despite the importance of this topic and the prevalence of this phenomenon, we lack
a mechanistic understanding of mRNA localization. A critical gap in our understanding pertains
to how mRNAs destined for localization are recognized by the cell and distinguished from non-
localizing mRNAs. In addition to sequences present within localizing mRNAs, the proteins that
bind these mRNAs are key to their cellular fate. This complex of proteins is responsible for
linking localizing mRNAs with molecular motors and for regulating their translation. However,
identifying these critical proteins has proven to be extremely challenging. By its very nature, the
process of mRNA localization is highly dynamic. Consequently, the protein-protein and protein-
RNA interactions required for assembling localizing messenger ribonucleoprotein (mRNP)
particles are weak and transient. This has made their identification using classical biochemical
approaches almost impossible; the complex falls apart during the purification step. In this
application, we propose novel strategies to address this critical knowledge gap. The model we
propose to use for these studies is the well characterized Drosophila melanogaster egg
chamber. In Objective 1 of this application, we propose to use proximity biotin ligation to define
the core components of transport particles and to examine the conservation of these factors
between flies and mammals. In Objective 2, we propose to test the hypothesis that granular
structures referred to as P bodies coordinate the localization of mRNAs with their translational
regulation.

## Key facts

- **NIH application ID:** 10693594
- **Project number:** 3R35GM145340-01S1
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Graydon Gonsalvez
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $11,305
- **Award type:** 3
- **Project period:** 2022-06-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693594

## Citation

> US National Institutes of Health, RePORTER application 10693594, Molecular mechanisms underlying the establishment of cell polarity. (3R35GM145340-01S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10693594. Licensed CC0.

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