# Deciphering mechanisms that drive collective cell migration

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $328,708

## Abstract

PROJECT SUMMARY
Collective cell migration is the most prevalent form of cell migration in the body; it is involved in the construction
and repair of almost all human tissues. Previous work by the PIs has provided novel insight on the hierarchy of
individual cell behaviors and intracellular signals that drive collective migration. This work identified activation of
the intracellular signal PLCg1 as strongly correlated with increased collective migration and cell migration
persistence. The proposed study aims to elucidate the mechanisms by which PLCg1 drives collective migration
and will yield both novel tools and knowledge that may be applied to control this process. We will achieve this
goal by:
 1) Determining the mechanism(s) by which PLCg1 activation yields cytoskeletal remodeling. We will develop
 a FRET-based PLCg1 reporter and identify the downstream effectors of PLCg1 that drive cytoskeletal
 rearrangement, a critical component of cell movement.
 2) Elucidating the biophysical mechanisms by which PLCg1 activation translates into directed collective
 migration. We will develop cellular models with varying levels of constitutively active PLCg1 and apply
 traction force microscopy to analyze how cytoskeletal forces are transmitted to yield collective cell
movement.
 3) Determining optimal patterns and extent of PLCg1 activation needed for robust collective migration. We
 will develop an optogenetic approach to stimulate different spatio-temporal dynamics of PLCg1 activation
 during directed keratinocyte migration.
By employing a combination of innovative molecular and biophysical tools, we aim to uncover mechanistic
knowledge that allows us to gain control over collective epithelial migration. Identifying the pathway(s) by which
PLCg1 activation connects to downstream signals, as well as its spatial and temporal dynamics within the
collective sheet, provides opportunities to regulate both healthy and pathological collective migration across a
range of tissues and pathologies. Elucidation of these pathways and cues provides an important foundation for
targeting specific elements to induce collective movement in conditions where it is impaired (e.g., chronic would
healing) or to halt collective movement in conditions where it is pathological (e.g., cancer).

## Key facts

- **NIH application ID:** 10928248
- **Project number:** 5R01GM143795-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Pamela K Kreeger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $328,708
- **Award type:** 5
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10928248

## Citation

> US National Institutes of Health, RePORTER application 10928248, Deciphering mechanisms that drive collective cell migration (5R01GM143795-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10928248. Licensed CC0.

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