The purpose of this Notice is to inform potential applicants to the National Institute on Drug Abuse (NIDA) of special interest in research examining transcriptomic, genomic, epigenomic, regulatory RNA, nuclear organization, or functional genomics to better understand Substance Use Disorder (SUD)-related biological processes.

Background

Dependence on addictive substances, including opioids, prescription drugs, nicotine, methamphetamine, cannabis, stimulants, and inhalants, is a major public health problem. Candidate genes or genetic/epigenetic variants involved in SUDs have been identified using human or animal genome-wide association scans, QTL characterization, gene expression profiling, forward or reverse genetic screens, or through transcriptomic, epigenomic, regulatory RNA or proteomic analyses. Genes and variants identified by these methods are priority targets for functional validation and further mechanistic characterization.

Research Objectives

Applicants may propose to identify, validate, and/or characterize genes, genetic or epigenetic variants, chromatin or nuclear features, or other molecular phenotypes associated with SUD-relevant biological processes or behaviors. It is anticipated that successful projects in this area will help us better understand the neurobiological mechanisms underlying SUDs and may also provide foundational knowledge to advance future SUD prevention, diagnosis, or therapeutic efforts. Applicants are encouraged to leverage the use of existing genetic resources whenever possible.

A gene or variant could manifest itself phenotypically at the level of a molecular pathway, cell, circuit, organism, or social interaction, leading to phenotypic differences in protein function, cell morphology, neural connectivity, behavioral responses to an addictive substance, or behavioral responses to social cues. NIDA encourages studies at any of these levels to identify phenotypic differences relevant to addictive processes and further elucidate the driving molecular pathways that converge to elicit biobehavioral changes. Applications through this NOSI may vary greatly in depth and breadth of analysis. For example, they may investigate a single high priority epigenetic or genetic variant in detail (e.g. using gene editing approaches) or test several hundred genes/variants rapidly (e.g. using high throughput RNA knockdown).

NIDA seeks to understand addiction to substances such as opioids, prescription drugs, nicotine, methamphetamine, cocaine, and cannabis. Applicants should therefore focus on one or more NIDA-relevant addictive substances. Applicants proposing to investigate alcohol in concert with one or more NIDA-relevant addictive substances may also submit their application through this NOSI.

Research interests include, but are not restricted to, the following:

• Human studies using DNA samples, post-mortem tissue, cell culture, induced pluripotent stem (iPS) cells, or in vivo imaging approaches
• Comparison of wild type and variant functions using in vivo genome or epigenome editing approaches, in vivo transgenes, in vitro biochemical assays, high-throughput approaches, systems biology, single cell approaches, or other methods
• Approaches that can ascribe a functional role to an epigenetic and/or genetic variant with respect to a particular aspect of addictive behavior or neurobiological function
• Projects exploiting established or emerging genetic models (e.g. C. elegans, Drosophila, zebrafish, rodent, non-human primate)
• Identification of cell type-specific or single cell level epigenomic or molecular features associated with addictive processes
• Exploitation of chromatin structure assays (e.g. Hi-C, ChIA-PET, ATAC-seq) or imaging techniques (e.g. seqFISH) to explore chromatin dynamics in response to addictive substances
• Studies investigating somatic genomic variation in response to addictive substances
• Studies to identify and characterize regulatory RNAs or extracellular RNA carriers (e.g. extracellular vesicles) relevant to neuroscience and addictive processes
• Molecular studies relevant to HIV infection, latency, or pathogenesis in the central nervous system

Application and Submission Information

This notice applies to due dates on or after June 5, 2020 and subsequent receipt dates through January 8, 2023.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

• PA-19-056 NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-19-091 NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

• PA-19-052 NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)

• PA-19-053 NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

• PA-18-591 Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp - Clinical Trial Optional)

• PAR-19-278 Exploiting Genome or Epigenome Editing to Functionally Validate Genes or Variants Involved in Substance Use Disorders (R21/R33 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-DA-20-031” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.

Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

John Satterlee, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: (301) 435-1020
Email: satterleej@nida.nih.gov

Financial/Grants Management Contact(s)

Aida Vasquez
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-2154
Email: vasquez@mail.nih.gov