# Mechanisms controlling cell size and shape

> **NIH NIH R35** · DARTMOUTH COLLEGE · 2024 · $585,939

## Abstract

PROJECT SUMMARY
The overall goal of NIGMS-funded research in my lab is to define the molecular and cellular
mechanisms that control cell size and shape. Defects in cell size and shape are associated with
human diseases including cancer, so defining the underlying mechanisms can identify future
therapeutic targets. We use the fission yeast S. pombe as a model system to study these
fundamental processes. These rod-shaped eukaryotic cells grow by linear extension due to
polarized secretion at growing cell tips, and enter mitosis at a highly reproducible size due to
regulated activation of the ubiquitous cyclin-dependent kinase Cdk1. Decades of genetic screens
have identified an extensive “parts list” for regulation of cell size and shape. Our current challenge
is to assemble these parts into defined signaling networks that spatially control cell growth and
activate Cdk1 in a size-dependent manner. For this work, we take a multidisciplinary approach
that combines genetics, quantitative live-cell microscopy, phosphoproteomics, and biochemical
reconstitution.
In this proposal, we will address four key unanswered questions. First, how do cortical multiprotein
clusters called “nodes” control fission yeast cell size at division? We discovered that nodes
contain conserved cell cycle regulators including the protein kinases Cdr2, Cdr1, and Wee1, but
we do not know the mechanisms of assembly or signal transduction within nodes. Second, what
is the role of multiple cell cycle pathways in monitoring aspects of cell size such as volume and
surface area? We will focus on the mitotic inducers Cdc25 and Cdc13/cyclin, with the goal of
generating systems-level knowledge supported by mathematical modeling. Third, how do cell
polarity mechanisms that function far away from the growing cell tips contribute to cell shape? We
will exploit our recent discoveries that implicate RNA granules and SNARE protein clusters as
novel “at-a-distance” regulators of cell polarity and shape. Fourth, how do cell size and shape
influence spatial patterning of nodes in cells? We have identified cell tips, cortical anchors, and
the nucleus as critical regulators of node positioning. We will combine genetic mutants with
quantitative fluorescence microscopy and particle-based simulations to define the underlying
design principles of this system. Based on extensive conservation of these pathways and
processes between yeast and mammals, we fully expect that discoveries from our work will impact
and guide future work in other organisms and biological systems.

## Key facts

- **NIH application ID:** 10934507
- **Project number:** 5R35GM149248-02
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** James B Moseley
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $585,939
- **Award type:** 5
- **Project period:** 2023-09-25 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10934507

## Citation

> US National Institutes of Health, RePORTER application 10934507, Mechanisms controlling cell size and shape (5R35GM149248-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10934507. Licensed CC0.

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