# Control of Cell Growth and Size

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2021 · $536,947

## Abstract

The goal of our work is to discover fundamental mechanisms that control cell growth and size in all
eukaryotic cells. Our recent work has focused on two key questions:
1. How do cells measure and limit growth to control cell size? In all cells, key cell cycle transitions
 occur only when sufficient growth has occurred, which ensures that proliferating cells maintain a specific
 size. Thus, cells must convert growth to a proportional signal that triggers cell cycle progression when it
 reaches a threshold. The mechanisms by which cells measure growth and trigger cell cycle transitions
 have remained deeply mysterious. Our recent work suggests that vesicles that drive plasma membrane
 growth deliver phosphatidylserine to the growing membrane, which recruits conserved signaling proteins
 to generate a signal that is proportional to the extent of growth. Furthermore, we discovered a signaling
 pathway that could read the growth-dependent signal and trigger cell cycle progression when it reaches
 a threshold. Growth-dependent signaling suggests a simple and broadly applicable solution to control of
 cell growth and size.
2. What are the signals that control cell growth and size? Observations reaching back over 60 years
 point to close relationships between control of cell growth and size. Thus, growth rate is proportional to
 nutrient availability, cell size is proportional to growth rate, and growth rate is proportional to cell size.
 These relationships appear to hold across all orders of life, which suggest that they reflect fundamental
 principles, yet the underlying mechanisms have remained elusive. We discovered that signals arising
 from a conserved TORC2 signaling network enforce proportional relationships between nutrient
 availability, cell growth, and cell size. For example, our work suggests that TORC2-dependent signals
 that set growth rate also set the threshold amount of growth required for cell cycle progression, which
 would provide a simple mechanistic explanation for the proportional relationship between cell size and
 growth rate.
Together, these new discoveries support transformational hypotheses that could broadly explain how cell
growth and size are controlled. In our future work, we will test the key hypotheses arising from our
discoveries, while also carrying out mechanistic analysis to further map the remarkable signaling networks
that control cell growth and size. We will also begin translating our discoveries in yeast into an
understanding of how cell growth and size are controlled in vertebrate cells.

## Key facts

- **NIH application ID:** 10200843
- **Project number:** 5R35GM131826-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Douglas R. Kellogg
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $536,947
- **Award type:** 5
- **Project period:** 2019-06-28 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200843

## Citation

> US National Institutes of Health, RePORTER application 10200843, Control of Cell Growth and Size (5R35GM131826-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200843. Licensed CC0.

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