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Single cell determinants of brain in the context of viral persistence in SIV/cART/cocaine non-human primates

Award Number: U01DA058402
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Drug abuse and HIV infection co-exist and are difficult to study due to challenges in people living with HIV (PLWH) who abuse drugs. One of the prime areas of pathogenic interactions of HIV and drugs of abuse is the brain, which carries additional study limitations. To obtain rigorous data on the effects of HIV and cocaine on the brain, we will utilize well-studied nonhuman primate animal model, Simian immunodeficiency virus (SIV)- infected and uninfected control rhesus monkeys, in the presence or absence of cocaine. Single cell sequencing assays enable cell type-specific analysis of the role of specific cell types in both healthy brain function and disease. The overall objective of this proposal by multidisciplinary team of investigators is to reveal the single cell determinants of brain in the context of viral persistence in SIV/cART/cocaine non-human primates. Simultaneous single-cell RNA sequencing and single-cell Assay for Transposase- Accessible Chromatin sequencing (scMultiome-seq) will be carried out on cells isolated from the prefrontal cortex (PFC), striatum, and hippocampus from each animal. Data will be processed and analyzed to derive cell type-specific regulatory programs and changes in these programs that regulate neuropathogenesis in the primate brains. These studies will provide unique and valuable insights into SIV/cocaine/cART interactions in the brain while also providing crucial experimental validation of the findings in humans. Successful completion of these innovative single-cell studies and data analyses methods will generate a single cell transcriptome and epigenome atlas of cellular part list for three NIDA-relevant brain regions, PFC, striatum, and hippocampus. These results will illuminate novel insights into transcriptomic and epigenetic landscapes of CNS and how they are altered by HIV and cocaine use.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $2,226,145 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Abuse and Addiction Research Programs	000	2	2/28/2024	NON-COMPETING CONTINUATION	$2,226,145
														Subtotal = $2,226,145

Issue Date FY: 2023 ( Subtotal = $2,494,069 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Drug Abuse and Addiction Research Programs	000	1	5/19/2023	NEW	$2,494,069
														Subtotal = $2,494,069

Grand Total All Awards = $4,720,214

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Single cell determinants of brain in the context of viral persistence in SIV/cART/cocaine non-human primates

Award Number: U01DA058402

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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