Cellular and Molecular Biology of Complex Brain Disorders (R21 Clinical Trial Not Allowed)
Can you apply?
This grant is for research institutions and organizations studying the cellular and molecular biology of complex brain disorders. Eligible applicants include universities (HBCUs, HSIs, TCCUs, and others), federal agencies, faith-based and community-based organizations, tribal governments, and non-U.S. entities.
Only R21-mechanism research is allowed (early-stage, exploratory, proof-of-concept). Clinical trials are not permitted. Researchers must have doctoral degrees appropriate for independent research.
The research focus is on high-confidence risk factors and their neurobiological mechanisms. Studies can use model organisms, human cell assays, or other experimental paradigms. Work must generate data suitable for common research resources and databases.
This grant is for research institutions and organizations studying the cellular and molecular biology of complex brain disorders. Eligible applicants include universities (HBCUs, HSIs, TCCUs, and others), federal agencies, faith-based and community-based organizations, tribal governments, and non-U.S. entities.
Only R21-mechanism research is allowed (early-stage, exploratory, proof-of-concept). Clinical trials are not permitted. Researchers must have doctoral degrees appropriate for independent research.
The research focus is on high-confidence risk factors and their neurobiological mechanisms. Studies can use model organisms, human cell assays, or other experimental paradigms. Work must generate data suitable for common research resources and databases.
Program description
This Notice of Funding Opportunity (NOFO) encourages research on the biology of high confidence risk factors associated with complex brain disorders, with a focus on the intracellular, transcellular and circuit substrates of neural function. For the purposes of this NOFO, the term complex can refer to a multifactorial contribution to risk (e.g., polygenic and/or environmental) and/or highly distributed functional features of the brain disorder. Studies may be either hypothesis-generating (unbiased discovery) or hypothesis-testing in design and may utilize in vivo, in situ, or in vitro experimental paradigms, e.g., model organisms or human cell-based assays. While behavioral paradigms and outcome measures can be incorporated into the research design to facilitate the characterization of intracellular, transcellular and circuit mechanisms, these are neither required nor expected. Studies should not attempt to model disorders but instead should aim to elucidate the neurobiological impact of individual or combined risk factor(s), such as the affected molecular and cellular components and their relationships within defined biological process(es). This can include the fundamental biology of these factors, components and processes. The resulting paradigms, component pathways and biological processes should be disseminated with sufficient detail to enrich common and/or federated data resources (e.g., those contributing to the Gene Ontology, Synaptic Gene Ontology, FAIR Data Informatics) in order to bridge the gap between disease risk factors, biological mechanism and therapeutic target identification. The present NOFO (R21 activity code) can be used for applications to develop early stage, high-risk, exploratory approaches or establish proof-of-concept where there is little or no preliminary data. Applicants proposing to develop lines of inquiry where feasibility or proof of concept has been established should apply to the companion R01 NOFO (PAR-xx-xxx).
Who can apply
Eligible applicants
- 501(c)(3) Public Charity
- City / Municipal Government
- County Government
- Faith-based Organization
- HBCU
- HSI (Hispanic Serving Institution)
- Nonprofits
- Private University
- Public Authority
- Public K-12 School
- Public University
- Researcher (independent)
- Small Business (SBA-defined)
- Special District
- State Government
- TCU (Tribal Colleges)
- Tribal Nation
- Tribal Organization
Details
This grant is for research institutions and organizations studying the cellular and molecular biology of complex brain disorders. Eligible applicants include universities (HBCUs, HSIs, TCCUs, and others), federal agencies, faith-based and community-based organizations, tribal governments, and non-U.S. entities.
Only R21-mechanism research is allowed (early-stage, exploratory, proof-of-concept). Clinical trials are not permitted. Researchers must have doctoral degrees appropriate for independent research.
The research focus is on high-confidence risk factors and their neurobiological mechanisms. Studies can use model organisms, human cell assays, or other experimental paradigms. Work must generate data suitable for common research resources and databases.
How to apply
Application links
Required documents
- SF-424 (R&D)
- Project Narrative
- Specific Aims
- Research Strategy
- Budget and Budget Narrative
- Biographical Sketch(es)
- Protection of Human Subjects (if applicable)
- Data Sharing Plan
- PHS Assignment Request Form
Program contact
- 👤 National Institutes of Health
- 📧 grantsinfo@nih.gov
- 📞 301-402-2541
Funding track record
Recent awards under CFDA 93.242 from the last 3 years — real organizations that won funding through this same program.
Top 10 Largest Recent Awards
-
$75,056,208
-
$74,756,329
-
$72,845,834
-
$64,705,159
-
$63,991,707
-
$54,214,022
-
$38,895,082
-
$38,475,557
-
$34,635,977
-
$34,475,710
Top States by Funding
- CA 15 awards $408.1M
- MA 9 awards $230.3M
- NY 6 awards $184.2M
- WA 4 awards $174.9M
- CT 3 awards $138.9M
Source: USAspending.gov — federal spending transparency. Data covers last 3 years.
Funding history
Annual funding for this program — Federal obligations (CFDA 93.242). How funding has trended year over year.
| 2024 | $1,722,300,004 | |
| 2025 | $1,726,864,191 | |
| 2026 est. | $99,221,272 |
FAQ
Who can apply for this grant?
Universities, HBCUs, HSIs, federal agencies, tribal organizations, faith-based organizations, and foreign organizations can apply. Individual researchers typically apply through their institutional research office.
Can clinical trials be included?
No. Clinical trials are not allowed under the R21 mechanism. Research must focus on cellular and molecular mechanisms, not patient studies.
What types of research designs are acceptable?
Both hypothesis-generating and hypothesis-testing studies work. Use model organisms, cell-based assays, or other experimental approaches. Clinical trials are excluded.
How does the R21 differ from the R01?
R21 funds early-stage, exploratory research with little preliminary data. R01 is for established feasibility. Check the companion R01 NOFO if your work has strong preliminary results.
What should data dissemination look like?
Share your findings with common databases like Gene Ontology or FAIR data resources. Provide sufficient methodological detail to benefit the broader research community.
💡 Tips for applicants
- Focus on mechanisms, not modeling. Explain how risk factors affect cellular and molecular processes, not how they recreate full disorder symptoms.
- Emphasize exploratory potential. Highlight novel methodologies and high-risk questions suitable for R21's early-stage mission.
- Detail data-sharing plans. Specify which public databases or repositories will receive your datasets and methods.
- Connect to therapeutic targets. Show how your mechanistic findings could eventually inform drug development or interventions.
- Build institutional support. Work with your research office early to ensure all compliance and regulatory documents are ready.
⚠️ Common mistakes
Proposing clinical trials or patient-based studies (R21 excludes clinical trials). Focusing on disease modeling rather than mechanistic biology of individual risk factors. Submitting to R21 when preliminary data is sufficient for R01.
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