Cellular and Molecular Biology of Complex Brain Disorders (R21 Clinical Trial Not Allowed) | PAR 24 025

Opportunity Information: Apply for PAR 24 025

The National Institutes of Health (NIH) is soliciting applications under the funding opportunity titled "Cellular and Molecular Biology of Complex Brain Disorders (R21 Clinical Trial Not Allowed)" (Funding Opportunity Number PAR-24-025; CFDA 93.242). This is a discretionary grant mechanism using the NIH R21 format, which is meant for exploratory, early-stage, and potentially higher-risk projects that can open up new research directions rather than deliver a fully mature, heavily validated program of work. The current listed closing date is 2026-09-07.

The scientific goal of the announcement is to push forward a clearer, more mechanistic understanding of how well-supported (high-confidence) risk factors for complex brain disorders affect neural function. "Complex" is used in a broad sense here: it can mean that risk is driven by many interacting factors (for example, polygenic contributions and/or environmental exposures) and it can also mean that the disorder involves widely distributed brain functions and circuitry rather than a single localized deficit. The emphasis is on biology that links risk factors to what is happening inside cells, between cells, and across circuits, essentially tracing a path from risk signal to concrete molecular, cellular, and circuit-level consequences.

The FOA allows both hypothesis-generating and hypothesis-testing approaches. On one end, applicants can propose unbiased discovery strategies that help identify impacted pathways, cell states, cellular interactions, or circuit-level changes associated with specific risk factors. On the other end, applicants can bring a focused mechanistic hypothesis and test it with targeted experiments. A wide range of experimental systems are considered appropriate, including in vivo studies in model organisms, in situ analyses in tissue, and in vitro approaches such as human cell-based assays. Behavioral tasks and behavioral outcomes can be included if they help illuminate intracellular, transcellular, or circuit mechanisms, but behavioral modeling is not the main expectation and is not required.

A key boundary set by the FOA is that projects should not aim to "model" the full disorder. Instead, the work should isolate and clarify the neurobiological impact of one or more risk factors. That means the central deliverable is not a disease model that recapitulates an entire diagnostic entity, but rather a detailed account of which molecular and cellular components are affected by the risk factor(s), how those components relate to one another within defined biological processes, and what that implies about mechanism. The FOA explicitly welcomes studies that also address the fundamental biology of the risk factors and their associated components and processes, so long as the research meaningfully supports the larger objective of connecting risk to mechanism in brain-relevant contexts.

Another important theme is dissemination in ways that help the broader community. NIH is signaling that the outputs of these projects should be described and shared with enough precision and structure that they can enrich common or federated data resources. Examples mentioned include resources contributing to the Gene Ontology, Synaptic Gene Ontology, and FAIR-aligned data informatics efforts. In practical terms, this encourages applicants to think beyond a single paper and toward producing reusable paradigms, well-annotated pathways, and clearly defined biological processes that others can integrate into shared knowledge frameworks. The larger purpose is to narrow the gap between identifying disease risk factors, understanding the mechanisms they disrupt, and ultimately enabling therapeutic target discovery.

The opportunity is open to a wide range of applicant organizations. Beyond typical academic and research institutions, eligible applicants include state, county, and local governments; special districts; independent school districts; federally recognized tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits (including 501(c)(3) and non-501(c)(3) entities); for-profit organizations (other than small businesses) and small businesses; and other categories. The FOA also highlights additional eligible groups such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, regional organizations, and non-U.S. (foreign) entities.

Finally, the "Clinical Trial Not Allowed" designation means applications should not propose clinical trials as defined by NIH. The work can still be highly relevant to human disease biology and may include human-derived cells or tissues, but the proposed research should remain in the preclinical or mechanistic domain rather than testing interventions in human participants under a clinical trial framework.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Cellular and Molecular Biology of Complex Brain Disorders (R21 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242.
• This funding opportunity was created on 2023-06-30.
• Applicants must submit their applications by 2026-09-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 24 025

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