# Determining how cell growth triggers cell division

> **NIH NIH R35** · STANFORD UNIVERSITY · 2022 · $610,135

## Abstract

The overarching goal of this project is to understand how cell growth triggers cell division in yeast and in
mammalian cells. Solving this question of has the potential to revolutionize our understanding of how cell division
is regulated in both natural developmental contexts and in disease. Our work has fundamental implications for
understanding how the most basic aspect of cell morphology, cell size, is controlled, and may identify novel
molecular mechanisms that can rationally be targeted in cancer therapies.
My laboratory recently made a breakthrough discovery in understanding how growth triggers division in budding
yeast. While it was expected that growth would act to increase the activities of the cyclin-dependent kinases
(Cdk) known to promote cell division, this is not the case. Rather, we found that cell growth acts in the opposite
manner. Cell growth triggers division by diluting a protein that inhibits cell division, Whi5.
This MIRA project aims to leverage our breakthrough discovery in understanding how growth triggers division in
yeast to understand the underlying transcriptional mechanism in yeast and to understand how this works in
mammalian cells. This is now possible thanks to the rapid advances in mammalian genome editing technologies
that allow us to tag cell cycle regulators at their endogenous loci. We can now measure, for the first time, the
dynamics of concentration changes of almost any protein expressed from its endogenous locus in individual
growing and dividing cells. To determine the mechanisms linking growth to division, we will examine how cell
size and growth impacts the concentration of key cell cycle regulators at single cell resolution. In addition, we
aim to examine transcription as a function of cell size genomewide in both yeast and diverse human cell types
to identify the underlying molecular mechanisms.

## Key facts

- **NIH application ID:** 10323005
- **Project number:** 5R35GM134858-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jan M Skotheim
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $610,135
- **Award type:** 5
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10323005

## Citation

> US National Institutes of Health, RePORTER application 10323005, Determining how cell growth triggers cell division (5R35GM134858-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10323005. Licensed CC0.

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