NIDA seeks to further advance its mission in the area of single cell biology.  Since 2020, the NIDA-funded Single Cell Opioid Responses in the Context of HIV (SCORCH) consortium has generated single-nucleus datasets from human and animal postmortem brain tissue under conditions of HIV infection, antiretroviral therapy (ART), and/or substance exposure (e.g. opioids, cocaine, methamphetamine, and cannabinoids).  Building on this Phase 1 foundation, NIDA will encourage research addressing critical questions on Substance Use Disorder (SUD) and interactions with HIV disease progression at the subcellular, cellular, or circuit levels in the Central Nervous System (CNS).  Many new cutting-edge single cell approaches (e.g. interrogation of RNA splicing, non-coding RNAs, epigenomic or proteomic features, subcellular or synaptic localization and function, spatial interactions, cell-cell communication, or cellular connectivity) now enable novel hypothesis-generating studies.  Along with data mining studies to identify candidate mechanisms or targets contributing to HIV/SUD interactions and hypothesis-driven studies to assess functional significance, we expect SCORCH Phase 2 to significantly advance our mechanistic understanding of SUDs and HIV in the CNS and identify targets for novel therapies.  Grant authorities that allow NIDA to forecast this opportunity are 42 U.S.C. §§ 241 and 284

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