# Identifying new ultrasound-sensitive proteins

> **NIH NIH R21** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2020 · $227,300

## Abstract

Abstract
Understanding brain function and developing therapies for neurological conditions requires an ability to
manipulate specific cell types non-invasively. The Chalasani lab has been developing a new technology using
low-frequency ultrasound to activate neurons engineered to express mechanosensitive channels
(“sonogenetics”). They have validated this approach in the nematode C. elegans and have obtained preliminary
data demonstrating its efficacy in rodents. This proposal is aimed at identifying additional ultrasound-sensitive
ion channels that are activated by different intensities and/or frequencies of ultrasound. Preliminary studies
conducted at the Marine Biological Laboratories identified five aquatic invertebrates (hydra, hydroid, barnacle,
octopus, and squid) that exhibit behavioral responses to ultrasound without microbubbles, which are typically
used to amplify the ultrasound stimulus. For instance, the colonial cnidarian hydroid (Hydractinia) responded to
a single 10-ms pulse of ultrasound (1.06–2.22 MPa peak negative pressure) by withdrawing its polyps. Using
publicly available sequencing data, the Edsinger lab obtained full-length sequence for the mechanosensory TRP
channel from this Hydractinia species. The Chalasani lab then synthesized the corresponding gene and showed
that it can be used to confer ultrasound responsiveness to mammalian cells both in vitro (assessed via calcium
indicators and electrophysiology) and in vivo (assessed using a feeding-behavior assay in mice). Success of this
pipeline motivates the two laboratories to analyze mechanosensory channel sequences (TRP-Ns, Piezo,
DEG/ENaC, and K2P) from the four other ultrasound-responsive species. The Edsinger lab will use either public
information, next generation sequencing data, or single-molecule long-read sequencing data to identify the
homologs of these mechanosensory proteins from the ultrasound-responsive species (Aim 1). The Chalasani
lab will synthesize these genes and test their ability to confer ultrasound sensitivity to HEK293 cells, to
mammalian neurons in vitro, and to neurons that regulate feeding behavior in vivo in mice (Aim 2). These studies
will expand the sonogenetics toolbox, identifying channels that are sensitive to a range of ultrasound intensities
in a microbubble-independent manner. Such a toolbox is vital for adapting this technology for use in a range of
species, including humans.

## Key facts

- **NIH application ID:** 9957129
- **Project number:** 5R21MH119646-02
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Sreekanth H. Chalasani
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $227,300
- **Award type:** 5
- **Project period:** 2019-06-17 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957129

## Citation

> US National Institutes of Health, RePORTER application 9957129, Identifying new ultrasound-sensitive proteins (5R21MH119646-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9957129. Licensed CC0.

---

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