# Optical Tools to Study Purinergic Signaling - Administrative Supplement

> **NIH NIH R01** · WELLESLEY COLLEGE · 2022 · $241,000

## Abstract

Project Summary/Abstract
Extracellular ATP and ADP are mediators of purinergic signaling in cell-to-cell communication in virtually every
tissue. Autocrine and paracrine purinergic signaling contributes to normal cellular functions such as immune cell
chemotaxis and cell volume regulation, and purinergic signaling also contributes to pathology in injury, infection,
sepsis, and a number of diseases. Notably, extracellular ATP and ADP mediate purinergic signaling between
cells with both short-term and long-term effects. However, it has been a challenge to study the cellular and
molecular mechanisms by which ATP and ADP control distinct signaling events because their levels are spatially
heterogeneous and purinergic signaling can vary significantly from cell-to-cell. Clearly, direct measurements of
extracellular nucleotides are needed, but current methods are not well adapted to measuring fluctuations in the
low extracellular nucleotide concentrations expected in live specimens. To overcome this barrier, we will use
protein engineering to develop high affinity cell-surface sensors that can be used to resolve the complex spatial
and temporal dynamics of ATP and ADP release, clearance, and purinergic receptor activation. To demonstrate
the application of our sensors and also guide their optimization, we will study neuron-glia purinergic signaling in
the brain. In particular, we will use our sensors to learn how metabolic state affects the function of microglia, the
resident immune cells in the brain, in regulating the regional purinergic dynamics that impact local neuronal
activity. The proposed series of multiplexed imaging studies that pair our purinergic sensors with sensors of
downstream signaling should directly visualize core elements of neuron-glia purinergic communication in an
integrated manner. This should provide valuable insight into novel mechanisms responsible for the coupling
between brain energy metabolism and excitability. Furthermore, the genetically-encoded tools developed
through this proposal should be broadly applicable to deeper study of any purinergic system.

## Key facts

- **NIH application ID:** 10580281
- **Project number:** 3R01GM134380-01A1S2
- **Recipient organization:** WELLESLEY COLLEGE
- **Principal Investigator:** Mathew Tantama
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $241,000
- **Award type:** 3
- **Project period:** 2022-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10580281

## Citation

> US National Institutes of Health, RePORTER application 10580281, Optical Tools to Study Purinergic Signaling - Administrative Supplement (3R01GM134380-01A1S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10580281. Licensed CC0.

---

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