# The Mechanism of Cell Size Regulation

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $335,000

## Abstract

PROJECT SUMMARY
How cells regulate their size is an long-standing biological mystery. Proper size regulation is
essential for cell viability. Dysregulation of cell size leads to cellular pathology and is
associated with human disease, particular malignancies. Yet, little is know about the
mechanisms of cell size regulation. We have recently made a important discovery regarding
cell size regulation in fission yeast: two direct activators of mitosis, the Cdc13 cyclin and the
Cdc25 phosphatase, are expressed in a size-dependent manner. This manner of expression is
unusual because most proteins maintain a constant concentration as cells grow. However, this
unusual behavior of two key cell cycle regulators supports the accumulating-activator
hypothesis of cell size control. The accumulating-activator hypothesis posits that size-
dependent accumulation of a limiting mitotic activator regulates cell size. The abundance of
such an activator restrains mitosis when cells are small and express low amounts of the
activator, but drives mitosis when cells are large and express high amounts of the activator. We
will directly test the hypothesis that Cdc25 and Cdc13 are redundant accumulating activators in
fission yeast. If they are, it will provide the first experimentally validated, mechanistic model
for size control in any organism. Even if size control is more complicated than just the
accumulation of Cdc25 and Cdc13, understanding the size-dependent accumulation of these
two key cell cycle regulators will provide important insight into the open question of how
proteins can be expressed in a size dependent manner. Therefore, we will dissect the regulation
of expression of both Cdc25, which we have shown to be regulated transcriptionally, and
Cdc13, which we have shown to be regulated post-transcriptionally.

## Key facts

- **NIH application ID:** 10125170
- **Project number:** 5R01GM134300-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** NICHOLAS R RHIND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $335,000
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10125170

## Citation

> US National Institutes of Health, RePORTER application 10125170, The Mechanism of Cell Size Regulation (5R01GM134300-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10125170. Licensed CC0.

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