# Cell-cycle-dependent cell polarity control

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE KNOXVILLE · 2021 · $297,857

## Abstract

PROJECT SUMMARY/ABSTRACT
Polarized cells in retain their shape in every cell cycle and this is essential to their proper function. Anomalies
in polarized cell shape can result in cancer, metabolic disorders, and loss of tissue integrity. Here, we will
investigate a long-standing question of how cells consistently regain their polarity after each round of division.
This investigation will be conducted using the fission yeast, Schizosaccharomyces pombe model system that
provides many well characterized genetic tools to manipulate conserved proteins that influence cell shape
following division. Cdc42 is the major regulator of polarized growth. In fission yeast, cells halt polarized Cdc42
activation and consequent growth at the cell ends during mitosis. After completion of division, these cell ends
resume Cdc42 activation and cell growth. After division, Cdc42 activation and polarized growth always
resumes in a monopolar manner from the old end that pre-exists from the previous generation. The cell
transitions to bipolar growth when Cdc42 activation also resumes at the newly formed cell end in the G2 phase
of the cell cycle. Our preliminary data indicate that resumption of Cdc42 activation at the old end after division
and transition to bipolar activation in G2 are cell cycle dependent. Our central hypothesis is that Cdc42 is
differentially regulated at the cell ends by distinct cell-cycle-dependent cues to establish the cell polarization
pattern. We will test this hypothesis by pursuing the following specific aims, [1] Determine how Cdc42
activation resumes at the cell ends in the G1/S phase; [2] Elucidate how a memory of growth from the previous
cell cycle enables the pre-existing old end to initiate Cdc42 activation first; [3] Explain how the transition from
monopolar to bipolar growth occur in G2 phase. With this project we expect to mechanistically understand how
Cdc42 activation and associated growth patterns are modulated in different cell cycle stages. We will examine
how signals from one cell cycle inform the growth pattern in the next generation. This will provide much needed
insights into the principles that preserve polarized cell shape in complex systems. Due to the conserved nature
of the proteins involved in this investigation, we expect that our findings will be relevant cell shape control in
higher eukaryotes and provide potential therapeutic or diagnostic targets for diseases such as cancer.

## Key facts

- **NIH application ID:** 10112928
- **Project number:** 5R01GM136847-02
- **Recipient organization:** UNIVERSITY OF TENNESSEE KNOXVILLE
- **Principal Investigator:** Maitreyi Das
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $297,857
- **Award type:** 5
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112928

## Citation

> US National Institutes of Health, RePORTER application 10112928, Cell-cycle-dependent cell polarity control (5R01GM136847-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10112928. Licensed CC0.

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