The Single Cell Opioid Responses in the Context of HIV (SCORCH) Program: Data Mining and Functional Validation R21 opportunity, issued by the National Institute on Drug Abuse (NIDA) under the National Institutes of Health (NIH), supports research that advances understanding of how HIV infection and addictive substances interact at the molecular level in the central nervous system. The grant specifically seeks projects that employ single-cell analysis technologies to mine existing data sets and/or conduct functional validation of key cell types, transcripts, enhancers, or transcriptional networks relevant to HIV/antiretroviral therapy (ART) and substance use disorders (SUDs).
The SCORCH consortium was established to generate and share harmonized single-nucleus RNA sequencing (snRNA-seq) and assay for transposase-accessible chromatin sequencing (snATAC-seq) data from human, non-human primate, and rodent brains. Data generation emphasizes comparison across four brain states: control, drug-exposed/SUD, HIV-positive, and HIV-positive with drug exposure. The objective is to uncover cell-type specific molecular mechanisms of HIV/ART and addiction that could reveal therapeutic targets. This NOFO encourages applications focused on mining SCORCH and related datasets using modern computational methods or performing high-throughput functional validation through transcriptomic, epigenomic, or spatial genomic approaches.
Projects must align with one or both of two major aims: identifying biologically relevant targets from single-cell datasets, and validating their roles using experimental models such as CRISPR interference, spatial genomics, or knock-in/out models. The program excludes studies focused solely on alcohol exposure or those lacking focus on HIV/SUD-relevant cell biology. Applicants must demonstrate expertise in single-cell data analysis, CNS impacts of HIV, and neurobiology of addictive substances.
The program uses the R21 Exploratory/Developmental mechanism for high-risk/high-reward studies that do not require preliminary data. The two-year project budget is capped at $275,000 in direct costs, with a limit of $200,000 in any one year. Clinical trials are not permitted. NIDA anticipates funding six to seven R21 or R01 projects per year under this and a companion NOFO, with total program funding of $3 million annually in FY2026 and FY2027.
The next application due date is March 19, 2026, with optional letters of intent due February 19, 2025. Applications must be submitted electronically through ASSIST, Grants.gov Workspace, or an institutional system-to-system platform. All required institutional registrations, including SAM, eRA Commons, and Grants.gov, must be completed before submission. The earliest project start date is expected in December 2026 following peer and advisory council reviews.
For inquiries, contact Dr. John Satterlee at satterleej@nida.nih.gov or 301-435-1020. Full application instructions, including data management and sharing plan requirements and scientific review criteria, are detailed in the official NOFO. This opportunity expired on November 20, 2025, but NIH may still accept submissions under its late or continuous submission policies on a case-by-case basis.