# Studies on cell polarity, chemotropism, and cell cycle control

> **NIH NIH R35** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2024 · $705,960

## Abstract

ABSTRACT
Our research is focused on fundamental questions related to cell polarity. Cell polarity describes the ability
of cells to spatially organize their internal constituents along a specific axis. It is critical for cell migration
(where cells need to generate a front and a back), and also for developing specialized cell shapes that are
needed for many cells to function. In addition, derangements of the polarity machinery can contribute to
several diseases, for example by enabling cancer metastases. Thus, an understanding of the mechanisms,
regulation, and consequences of cell polarity is of both fundamental and medical interest.
Studies on cell polarity have identified an evolutionarily ancient and conserved core machinery centered on
a primary regulator of polarity called Cdc42. However, many of the most interesting questions remain
unsolved. How is it that most cells only make a single “front” enriched in Cdc42, but some cells with more
complex shapes can specify several sites to act as fronts? How do cells read their environment to
determine the direction in which they should orient the polarity axis? Once polarity is established, how is the
precise downstream set of events orchestrated to give each cell type the right shape? And then, how do
cells know what shape they are?
We use the uniquely tractable yeast model system to investigate these questions, and apply a combination
of cutting-edge microscopy, genetics, and computational modeling. Our previous work identified a positive
feedback mechanism that explains how Cdc42 becomes concentrated at polarity sites to establish a polarity
axis. Our recent work on polarization during yeast mating, when yeast cells orient in response to spatial
gradients of pheromones, suggests a new paradigm, called Exploratory Polarization, for tracking chemical
gradients. And new findings on marine fungi reveal novel lifestyles whose cell biology has yet to be
characterized. For the next 5-year grant cycle, our major goals are to (i) address how cell polarity is
regulated by cell cycle and pheromone signaling; (ii) address remaining open questions about the new
exploratory polarization mechanism that enables mating cells to find each other, and (iii) to understand how
marine fungi that make several buds in each cell cycle can partition their nuclei and organelles among the
different buds. We are poised to make significant advances on the questions posed above, and to exploit
the answers to those questions to provide insights that extend well beyond the yeast system.

## Key facts

- **NIH application ID:** 10879004
- **Project number:** 5R35GM122488-09
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** DANIEL J LEW
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $705,960
- **Award type:** 5
- **Project period:** 2017-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879004

## Citation

> US National Institutes of Health, RePORTER application 10879004, Studies on cell polarity, chemotropism, and cell cycle control (5R35GM122488-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10879004. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*