Funding Opportunity Number: RFA-DA-26-001
Deadline: February 19, 2025
Purpose
The purpose of this notice of funding opportunity (NOFO) is to support data mining of single cell data sets to identify cell types, transcripts, enhancers, or transcriptional networks that play a role in HIV/ART and SUD-relevant molecular responses, and/or to support functional validation studies (e.g. epigenomic or transcriptomic manipulation, high throughput secondary screening) to confirm or deny a biological role for one or more of the data-mined cell types, transcripts, enhancers, or transcriptional networks in HIV/ART and SUD molecular responses.
Applications Not Responsive to this NOFO.
The following types of studies are not responsive to this NOFO and will not be reviewed:
- Studies whose major thrust does not include either A or B.
- A. Studies proposing data mining of single nucleus data sets from SCORCH, BRAIN, HubMap, other public sources, and/or their own work to identify cell types, transcripts, pathways, and/or enhancers involved in responses to HIV infection, replication, latency, pathogenesis (including neuroHIV cognitive phenotypes), and/or antiretroviral therapy.
- B. Studies proposing functional validation of one or more cell types, candidate transcripts, pathways, and/or enhancers for potential roles in HIV infection, replication, latency, pathogenesis, and/or antiretroviral therapy.
- Studies that do not include at least one aim or sub-aim involving either:
- 1. opioid, cannabinoid, nicotinic, dopaminergic, or other signaling pathways relevant to addictive substance use, or
- 2. exposure to addictive substances, or
- 3. analysis of samples from patients that have used addictive substances or have SUDs. Substances of interest include nicotine, cocaine, methamphetamine, other stimulants, opioids, addictive prescription drugs, cannabinoids, or combinations of drugs.
- Studies focused solely on alcohol exposure.
Selection of R21 or R01 NOFO: Although identical in scientific thrust, this NOFO (RFA-DA-26-001) supports R01 projects for which applicants should provide evidence that they can perform the proposed techniques or analyses. However, R01 applicants are NOT required to have pilot preliminary data in an HIV or SUD system for the proposed transcripts, enhancers, or pathways to be tested. RFA-DA-26-002 supports high risk/high reward R21 applications for which neither technical nor pilot preliminary data are required.
Other considerations**.** Applicants are encouraged to contact program staff with their questions. We anticipate interdisciplinary teams will be necessary for successful completion of the proposed work. Such teams should include expertise in the analysis of single cell data, HIV persistence or effects on the CNS, and the effects of addictive substances on the CNS.
Some types of studies that would be appropriate for this NOFO include, but are not limited to:
Data mining
- Data mining of single nucleus or spatial genomics data sets using machine learning, neural networks, artificial intelligence, etc.
- Data mining across species (e.g. rat, mouse, non-human primates, and/or human) to identify conserved transcripts, pathways, or enhancers.
- Integration of investigator-initiated single cell data with existing single cell and other molecular data sets (e.g. epigenomic, proteomic) including those from cell culture, invertebrates, rodents, primates, the SCORCH program, and/or other projects that involve opioid, methamphetamine, cocaine, cannabinoid, or polysubstance exposure and/or HIV-relevant models.
- Data mining of SCORCH single nucleus data in concert with datasets from spatially and/or functionally resolved cellular assemblies relevant to HIV or addiction. Examples include but are not limited to anatomical structures, functional networks, and ensembles such as those characterized by projects funded through the NIDA NExUS Collaboratory on Neural Ensembles & Used Substances
- Identification of molecular differences, if any, between immune or other cells found in both brain and blood.
Functional Characterization
- Manipulation and functional characterization of high priority cell types, transcripts, promoters, or enhancers to validate their role in HIV and addictive processes.
- Functional testing of one or many potentially relevant transcripts or enhancers using cell culture, animal models, organoids, or other models or strategies.
- Characterization of cell types, transcripts, or enhancers using spatial genomics approaches.
- Development of viral vectors or related reagents to probe or manipulate cell, transcript, or enhancer functions.
- Functional validation or characterization of several or many nominated transcripts or enhancers using CRISPR interference, CRISPR activation, epigenome editing, RNA editing, or other high-throughput genomic manipulation techniques.
- Use of genome or epigenome editing technologies to generate knock-in or knock-out animals or human organoids for functional characterization.
- Testing the functional effects of a transcript or enhancer on molecular phenotypes such as gene expression, epigenetic modification, transcription factor binding, 3D chromatin structure, etc.
For more information, please see the opportunity webpage.