Atom | Functional Validation and/or Characterization of Genes or Variants Implicated in Substance Use Disorders (R21/R33 Clinical Trial Not Allowed)

Due Dates: March 3, 2025 (New, Renewal, Resubmission, Revision) | July 28, 2025 (New, Renewal, Resubmission, Revision)

Funding Amounts: Up to $125,000/year (R21 phase, max 2 years); up to $250,000/year (R33 phase, max 3 years); total project period up to 5 years.

Summary: Supports functional validation and characterization of genes or variants implicated in substance use disorders using genome or epigenome editing, with resources made broadly available.

Key Information: Clinical trials are not allowed; generated genetic resources must be shared with the scientific community.

Description

This NIH funding opportunity supports research projects that functionally validate and/or characterize genes or genetic/epigenetic variants implicated in substance use disorder (SUD)-relevant phenotypes. The initiative emphasizes the use of genome or epigenome editing technologies (e.g., CRISPR, epigenome editing, iPS systems) to confirm and explore the roles of candidate genes or variants identified through genetic, transcriptomic, or epigenomic studies. The ultimate goal is to provide foundational knowledge for future prevention, diagnostic, and therapeutic strategies for SUDs, and to make any genetic resources generated broadly available to the research community.

The program uses a phased R21/R33 mechanism:

R21 phase: High-risk, milestone-driven exploratory work (up to 2 years).
R33 phase: Expanded, in-depth characterization (up to 3 years), contingent on successful completion of R21 milestones.

Projects may include orthogonal validation of candidate genes/variants, mechanistic studies in model organisms or human organoids, and functional characterization of addiction-relevant phenotypes. Alcohol-only studies are not eligible; focus must be on substances relevant to NIDA (e.g., nicotine, cocaine, stimulants, opioids, cannabinoids).

Due Dates

March 3, 2025: New, renewal, resubmission, and revision applications due.
July 28, 2025: New, renewal, resubmission, and revision applications due.
Letter of Intent: 30 days prior to application due date (optional but encouraged).

All applications are due by 5:00 PM local time of the applicant organization.

Funding Amount

R21 phase: Up to $125,000 per year in direct costs (max 2 years).
R33 phase: Up to $250,000 per year in direct costs (max 3 years).
Total project period: Up to 5 years.
Transition to R33: Based on successful completion of R21 milestones; not all projects will advance to R33.

Eligibility

Eligible applicants include:

Public and private institutions of higher education
Nonprofits (with or without 501(c)(3) status)
For-profit organizations (including small businesses)
State, county, city, township, and special district governments
Independent school districts
Native American tribal governments and organizations (federally recognized and other)
Public housing authorities/Indian housing authorities
Faith-based and community-based organizations
Regional organizations
U.S. territories and possessions
Non-domestic (non-U.S.) entities (foreign organizations) and foreign components of U.S. organizations

Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are eligible to apply as PD/PI.

Application Process

Submission: Applications must be submitted electronically via Grants.gov, NIH ASSIST, or an institutional system-to-system solution.
Required Registrations: Applicant organizations must have active registrations in SAM.gov, eRA Commons, and Grants.gov.
Letter of Intent: Optional, but recommended; submit to NIDALetterofIntent@mail.nih.gov.
Application Guide: Follow the NIH How to Apply - Application Guide and the specific instructions in the funding announcement.
Resource Sharing Plan: All applicants must provide a plan for broad sharing of any genetic resources generated.
Data Management and Sharing Plan: Required for all applications.

Additional Information

Clinical Trials: Not allowed under this opportunity.
Scope: Projects must focus on functional validation/characterization, not discovery of new genes/variants.
Model Systems: May include invertebrates, zebrafish, rodents, primates, or human organoids.
Substance Focus: Must include addictive substances relevant to NIDA; alcohol-only studies are not eligible.
Resource Sharing: All genetic resources (e.g., transgenic animals, cell lines) generated must be made broadly available to the scientific community.
Review Criteria: Scientific merit, innovation, feasibility, investigator expertise, and resource sharing plans are key review factors.

External Links

Contact Information

Topic	Contact/Resource
General Grants Info	GrantsInfo@nih.gov \| 301-480-7075
Application Submission Help	eRA Service Desk \| 301-402-7469 or 866-504-9552
Grants.gov Support	support@grants.gov \| 800-518-4726
Scientific/Research Contact	John Satterlee, Ph.D., NIDA, satterleej@nida.nih.gov \| 301-435-1020
Peer Review Contact	NIDA Review, NIDAPeerReview@nih.gov
Grants Management Contact	Chief Grants Management Officer, NIDA, nidagmbemail@nida.nih.gov