# ATAC-ing dopaminergic cell identity with single-cell resolution

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $228,750

## Abstract

Dopamine neurons are a critical component of reward pathways in the brain. Historically, dopamine neurons
were considered a relatively homogeneous population mediating association of reinforcement signals from
food, water, and reproduction with coinciding sensory stimuli. However, recent studies have shown that these
neurons form subpopulations with distinct physiological profiles, neural projections, and biological functions.
These distinct subpopulations also have different roles in the progression of the addiction cycle, from use to
abuse, abstinence and relapse. The goal of this application is to engineer novel genetic tools that will allow
precise manipulation of distinct subpopulations of dopamine circuits, with specificity down to single pairs of
neurons. To this end we will first apply a new technique, single-cell ATAC-seq, to determine all open
chromatin/accessible DNA enhancer elements of every one of the ~250 dopamine neurons in the Drosophila
brain. Second, we will determine which open enhancer fragments, or combinations thereof, will uniquely
identify single dopamine cells/cell-types. And third, based on this analysis, we will engineer numerous new
genetic tools and test them for their in vivo efficacy and specificity. While these Aims are linear and fully
interdependent, the grant overall applies the very new technique of single-cell ATAC-seq to “break new
ground” and “accelerate the pace of discoveries to advance addiction research”. The proposal essentially tests
the hypothesis that this unbiased, genome-wide approach can be harnessed to generate new tools for
precision intervention. Because the approach itself can be scaled, applied to any cell type, and translated to
mammals, this application is fully consistent with the spirit of the Cutting-Edge Basic Research Awards
(CEBRA) mechanism, which will “support high-risk, high impact research” (PAR-18-437).

## Key facts

- **NIH application ID:** 9980840
- **Project number:** 5R21DA049635-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Adrian Rothenfluh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,750
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980840

## Citation

> US National Institutes of Health, RePORTER application 9980840, ATAC-ing dopaminergic cell identity with single-cell resolution (5R21DA049635-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9980840. Licensed CC0.

---

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