Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain
About This Grant
Neurogenomic studies by the SCORCH (Single Cell Opioid Response in the Context of HIV) consortium strongly suggest that brains of individuals living with HIV in the context of opioid or (polys)substance use disorder (OUD/SUD) comorbidity harbor a molecular environment permissive for HIV viral replication and risk for cytotoxic damage. This conclusion also applied to donors who showed systemic, antiretroviral drug- mediated suppression of the virus. There was a stepwise progression of transcriptomic dysregulation in OUD+HIV+ brain, culminating in widespread neuronal pathology and pronounced inflammatory signatures in microglia from individuals with poor viral suppression. The goals of the current project are two-fold. First, we aim for single molecule validation of SCORCH single cell results, by analyzing~12-20kb single molecule fiber- seq libraries from cingulate cortex of SCORCH brains carefully annotated for OUD/SUD and systemic (HIV) suppression status. We will embark on single fiber-level multiomic profiling with differential analyses to uncover effects of HIV infection on nucleosome phasing, positioning and offset at transcription start sites, together with endogenous m5CpG methylation and transcription factor footprints. Integrating single cell (RNA+ATAC-seq) data already generated from the same set of SCORCH brain cohort, with our new single molecule multiomic fiber-seq mappings is expected to provide unprecedented neurogenomic insights into the HIV and substance-exposed brain. Second, we aim for additional functional validation of SCORCH data, by employing HIV-induced lineage tracing (HILT) in human induced pluripotent stem cell (hiPSC)-derived Neuron-Astrocyte-Microglia (hiPSC N-A-Mg) tricultures, in conjunction with CRISPRi for multiplexed microglial promoter repression focused on genes that are both (i) dysregulated in SCORCH SUD+ postmortem brain and (ii) implicated in HIV expression or replication. We will assess viral integration frequency, numbers and proportions of infected microglia, and compare transcriptomes and chromatin of infected/integrated HIV+ microglia with those from exposed bystander cells. This project is a first step to validate SCORCH genomic discoveries on the single molecule level, followed by the design of novel therapeutic tools targeting opioid/substance-dysregulated genes that could foster HIV infection and spread in the brain.
Grant Summary
Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain is a NIDA - National Institute on Drug Abuse grant providing up to $2.4M for university, nonprofit, healthcare org. Applications are due 2030-01-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $2.4M
2030-01-31
- 1Confirm your organization is eligible for Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain from NIDA - National Institute on Drug Abuse, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIDA - National Institute on Drug Abuse before the deadline.
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Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain: Frequently Asked Questions
Who is eligible for the Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain?
Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain is offered by NIDA - National Institute on Drug Abuse and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain provide?
Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain provides up to $2.4M per award from NIDA - National Institute on Drug Abuse. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain deadline?
Applications for Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain are due 2030-01-31 (open). Because deadlines can change, verify the date with the funder, NIDA - National Institute on Drug Abuse, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain?
To apply for Single molecule functional validation of neurogenomic alterations in opioid-exposed HIV brain, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIDA - National Institute on Drug Abuse.