A Multiomic Single Nucleus RNA-seq and ATAC-seq Examination of Key Brainstem Respiratory Control Regions from Fentanyl Overdose Decedents with and without Xylazine Present, and Matched Controls
About This Grant
Over 81,000 individuals died of an opioid overdose (OD) in 2023, and >92% of those cases involved fentanyl. Fentanyl has very potent opioid-induced respiratory depression (OIRD) effects, the primary cause of opioid OD death. Key brainstem regions, the preBötzinger complex and ventral respiratory group (preBot/VRG) and parabrachial and pontine Kölliker-Fuse nuclei (PB/KFn), play critical roles in respiration, and have been implicated in OIRD. Therefore, it is likely that the cellular etiology of opioid OD, notably the sites of action of fentanyl, involves these understudied brain regions. Despite evidence for individual differences including heritable variation in opioid OD (e.g., our GWAS of opioid OD death), most biologically mechanistic studies have focused on addiction-centric brain regions. Consistent with the likelihood of differential cellular signatures across these brain regions, our preliminary data suggest pervasive bulk tissue expression differences in the preBot (i.e., genes distinct from those implicated in regions relevant to addiction). In addition, prior studies have primarily relied on bulk tissue or single omics approaches to characterize the cellular etiology of opioid OD death. New multiome methods allow us to deeply characterize how the partnership between chromatin accessibility and gene expression in these brain regions drives opioid OD involving fentanyl, thus offering insights into biology and implicating genes that could be therapeutically targeted. Against the backdrop of unabated fentanyl-driven OD deaths, our proposal will: (A) generate the first single-nucleus (sn) paired RNAseq and snATACseq (i.e., multiome) data from the preBot/VRG and PB/KFn, from diverse human fentanyl OD decedents (N=40) and matched controls (N=40). (B) Characterize cell populations, states and cell-type specific relationships between differential gene expression and chromatin accessibility in each brain region across groups. (C) Estimate enrichment of opioid GWAS variants and genes, yielding mechanistic insights to large-scale population-scale genetic discovery. (D) Combine existing opioid-related expression differences in the same and other brain regions to delineate a brain-wide network of transcriptional variability associated with OUD and opioid OD, and produce in-silico prioritization of gene-drug pairs that are viable for preclinical follow-up.
Grant Summary
A Multiomic Single Nucleus RNA-seq and ATAC-seq Examination of Key Brainstem Respiratory Control Regions from Fentanyl Overdose Decedents with and without Xylazine Present, and Matched Controls is a NIDA - National Institute on Drug Abuse grant providing up to $578K for university, nonprofit, healthcare org. Applications are due 2030-11-30 (open). Check eligibility and apply with FindGrants.
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Up to $578K
2030-11-30
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A Multiomic Single Nucleus RNA-seq and ATAC-seq Examination of Key Brainstem Respiratory Control Regions from Fentanyl Overdose Decedents with and without Xylazine Present, and Matched Controls: Frequently Asked Questions
Who is eligible for the A Multiomic Single Nucleus RNA-seq and ATAC-seq Examination of Key Brainstem Respiratory Control Regions from Fentanyl Overdose Decedents with and without Xylazine Present, and Matched Controls?
A Multiomic Single Nucleus RNA-seq and ATAC-seq Examination of Key Brainstem Respiratory Control Regions from Fentanyl Overdose Decedents with and without Xylazine Present, and Matched Controls 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 A Multiomic Single Nucleus RNA-seq and ATAC-seq Examination of Key Brainstem Respiratory Control Regions from Fentanyl Overdose Decedents with and without Xylazine Present, and Matched Controls provide?
A Multiomic Single Nucleus RNA-seq and ATAC-seq Examination of Key Brainstem Respiratory Control Regions from Fentanyl Overdose Decedents with and without Xylazine Present, and Matched Controls provides up to $578K 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 A Multiomic Single Nucleus RNA-seq and ATAC-seq Examination of Key Brainstem Respiratory Control Regions from Fentanyl Overdose Decedents with and without Xylazine Present, and Matched Controls deadline?
Applications for A Multiomic Single Nucleus RNA-seq and ATAC-seq Examination of Key Brainstem Respiratory Control Regions from Fentanyl Overdose Decedents with and without Xylazine Present, and Matched Controls are due 2030-11-30 (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 A Multiomic Single Nucleus RNA-seq and ATAC-seq Examination of Key Brainstem Respiratory Control Regions from Fentanyl Overdose Decedents with and without Xylazine Present, and Matched Controls?
To apply for A Multiomic Single Nucleus RNA-seq and ATAC-seq Examination of Key Brainstem Respiratory Control Regions from Fentanyl Overdose Decedents with and without Xylazine Present, and Matched Controls, 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.