The National Institute on Drug Abuse (NIDA) is issuing the Single Cell Opioid Responses in the Context of HIV (SCORCH) Program: Data Mining and Functional Validation (R21) funding opportunity to support exploratory research on molecular responses to substance use disorders (SUDs) and HIV/antiretroviral therapy (ART) at the single-cell level. This opportunity seeks to fund studies that mine existing single-cell datasets to identify specific cell types, transcripts, enhancers, or transcriptional networks linked to molecular responses relevant to HIV, ART, and SUDs. Additionally, it supports functional validation of these targets to confirm their role in disease mechanisms. The program does not require preliminary data and focuses on high-risk, high-reward studies that can advance understanding of HIV and addiction at a cellular resolution.

The SCORCH program, a consortium established by NIDA, has already generated brain single-nucleus RNA sequencing (snRNA-seq) and ATAC-seq data from different cohorts, including control, drug-exposed, HIV-positive, and HIV-positive with SUD samples across human, rodent, and non-human primate models. This NOFO (R21) encourages the integration of SCORCH data with other publicly available datasets and supports projects using machine learning, artificial intelligence, and cross-species data integration to elucidate conserved pathways. Functional validation can involve various molecular techniques, including CRISPR, RNA editing, and spatial genomics, to test the impact of identified molecular targets on SUD and HIV pathways.

Applicants must include a Plan for Enhancing Diverse Perspectives (PEDP) in their application, outlining strategies for integrating diverse scientific expertise and perspectives into the research team. This PEDP requirement is part of the NIH’s commitment to fostering inclusive research environments that leverage diverse backgrounds and expertise to drive scientific innovation and discovery.

The program anticipates awarding approximately six to seven projects (including those funded under a related R01 mechanism) each year in 2026 and 2027, with a combined budget cap of $275,000 in direct costs over the two-year project period. Eligible applicants include higher education institutions, nonprofit organizations, for-profit organizations, local governments, and other entities, including foreign institutions. Projects must be scientifically distinct from each other, and applicants are encouraged to form interdisciplinary teams with expertise in single-cell analysis, HIV, CNS pathology, and addiction research to maximize the potential impact of the studies.

Applications will be evaluated based on the significance and innovation of the research, the rigor and feasibility of the proposed approach, and the qualifications of the research team. Reviewers will also assess the project’s PEDP to ensure that diversity is integrated meaningfully into the research process. Applications that do not include a PEDP will be deemed incomplete and withdrawn from review.

The first application due date is March 19, 2025, with subsequent review and funding cycles through March 2026. Applications must be submitted via Grants.gov, and all applicants are advised to ensure compliance with NIH submission guidelines. For assistance, applicants may contact NIH staff listed in the funding announcement. The award period is up to two years, and awardees will be required to report annually on the implementation of their PEDP and data-sharing plans as part of NIH’s commitment to fostering scientific transparency and accessibility.