# New Chemical Tools for Exploring Cellular Physiology

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $220,906

## Abstract

Abstract
New Chemical Tools for Visualizing Cellular Physiology
The cell membrane is the only organelle shared by all varieties of cellular life. Unequal distribution of ions
and chemical species across the plasma membrane results in the generation of an electrochemical
potential, and rapid changes in this membrane potential, or voltage, drive the unique physiology of
excitable cells like neurons and cardiomyocytes. However, all cells, even non-excitable cells, possess a
membrane potential, and mounting evidence supports a role for membrane potential in controlling
fundamental cellular physiology—for example, cell cycle, migration, proliferation, and differentiation—in
non-excitable cells. Despite the central role of membrane potential to the cellular physiology of both
excitable and non-excitable cells, our understanding of membrane potential in these systems remains
incomplete, due in large part to a lack of tools for studying cellular physiology with high spatial and
temporal resolution. Measurements of membrane potential rely on highly invasive, low throughput direct
voltage recording through electrodes (patch clamping) or by indirectly monitoring the down-stream effects
of membrane potential via imaging (Ca2+ imaging). We propose to use the power of synthetic organic
chemistry to design fluorescent voltage sensors to probe membrane potential dynamics in neurons and
cardiomyocytes, in addition to non-excitable cells. In a complementary approach, we are developing
small molecule-based activity integrators that integrate Ca2+ transients over time to enable high resolution
reconstruction of cellular activity during a specified time window—at length scales (superresolution
microscopy, electron microscopy) that are not accessible with currently available sensors.
Although many of the tools we are developing have applications in neuroscience, these strategies and
techniques can be applied to fundamental cellular physiology. Additionally, my research program places
a heavy emphasis on synthetic chemistry and molecular design to achieve our goals. I anticipate we will
uncover fundamental insights in areas related to photoinduced electron transfer, supramolecular
chemistry, physical organic chemistry, and biophysics as we design and develop these new tools.

## Key facts

- **NIH application ID:** 9981758
- **Project number:** 5R35GM119855-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Evan Walker Miller
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $220,906
- **Award type:** 5
- **Project period:** 2016-07-22 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981758

## Citation

> US National Institutes of Health, RePORTER application 9981758, New Chemical Tools for Exploring Cellular Physiology (5R35GM119855-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9981758. Licensed CC0.

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