# Extracellular optogenetic control in the study of epithelial collective cell signaling

> **NIH NIH F32** · PRINCETON UNIVERSITY · 2020 · $10,885

## Abstract

Project Summary
 Cell signaling in multicellular tissues is extraordinarily complex, ensuring that cells coordinate their
proliferation, survival and movement for proper tissue function. One model context for multicellular signaling is
the skin, an important organ that remains highly proliferative throughout the life of the animal and must balance
this constant proliferation and repair with tight regulation to prevent tumorigenesis. Recent work using a live-cell
Erk biosensor has revealed complex tissue-level signaling dynamics in epidermal tissues, both in cell culture
and in living mammals. Taken together with previous studies showing that Erk signaling is both necessary and
sufficient for wound healing and skin cell proliferation suggests that cells share crucial information through the
local transmission of complex, dynamic growth factor signals.
 The current proposal aims to shed new light on growth factor signaling by developing optogenetic tools to
activate and inhibit growth factor receptors with high precision. Current optogenetic approaches modulate
signaling dynamics by altering intracellular protein activity, which requires substantial genome engineering and
thus has limited use in vivo or as a therapeutic approach. In contrast, we have devised two new photosensitive
tools to modulate cell signaling from the extracellular environment. We will engineer light-controllable ligands
and inhibitors against receptor tyrosine kinases, to enable spatial and temporal control over the signals
transmitted between cells. We will then use these tools to dissect complex Erk dynamics in primary mouse
keratinocytes, a model system for the mammalian epidermis. Achieving a better understanding of the complex
signals transmitted between cells will enable future studies to dissect their roles in wound healing and skin
cancer. Additionally, the development of new optogenetic systems for manipulating extracellular binding events
could lead to highly generalizable tools with the potential to control many other cellular processes.

## Key facts

- **NIH application ID:** 10213975
- **Project number:** 3F32GM128304-02S2
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Agnieszka Gil
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $10,885
- **Award type:** 3
- **Project period:** 2018-06-01 → 2020-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213975

## Citation

> US National Institutes of Health, RePORTER application 10213975, Extracellular optogenetic control in the study of epithelial collective cell signaling (3F32GM128304-02S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10213975. Licensed CC0.

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