Cellular and Molecular Biology of Complex Brain Disorders (R21 Clinical Trial Not Allowed) | PAR 25 037

Opportunity Information: Apply for PAR 25 037

The NIH grant opportunity "Cellular and Molecular Biology of Complex Brain Disorders (R21 Clinical Trial Not Allowed)" (Funding Opportunity Number PAR-25-037; CFDA 93.242) supports early-stage, exploratory research aimed at clarifying how well-supported (high confidence) risk factors for complex brain disorders actually work at the biological level. The emphasis is on mechanisms that operate within cells (intracellular), between cells (transcellular), and across neural circuits, with the goal of connecting disease risk signals to concrete molecular and cellular processes that can later inform therapeutic target discovery. "Complex" is used broadly here and can mean risk that arises from many contributors (for example, polygenic architectures and/or environmental exposures) and/or disorders whose functional features are distributed across multiple brain systems rather than localized to a single site.

The NOFO is intentionally focused on studying risk factors rather than trying to recreate or "model" full disorders. Applicants are expected to investigate the neurobiological impact of individual risk factors or combinations of risk factors, identifying what molecular and cellular components are affected and how those components relate within defined biological processes. This can include foundational work on the basic biology of implicated genes, pathways, synapses, cell types, or circuit operations, as long as the project is oriented toward mechanistic understanding of risk rather than symptom-level disease modeling. Behavioral tasks and behavioral outcome measures can be included if they help interpret cellular or circuit mechanisms, but they are not required and are not the main expected deliverable.

Methodologically, the program allows a wide range of experimental approaches as long as they are appropriate for mechanistic work at cellular and circuit scales. Projects may be hypothesis-generating (for example, unbiased discovery strategies) or hypothesis-testing, and may use in vivo, in situ, or in vitro paradigms. That includes work in model organisms as well as human cell-based assays (such as patient-derived or engineered cellular systems), provided the research question stays centered on how risk factors alter biology at the levels this NOFO prioritizes. Clinical trials are not allowed under this announcement, which signals that the funder is looking for preclinical and mechanistic research rather than interventional studies in human participants designed to test clinical outcomes.

A distinctive expectation in this NOFO is that the outputs should be shared in ways that strengthen community data resources and enable broader reuse. Applicants are encouraged to disseminate the resulting paradigms, component pathways, and biological processes with enough structure and detail to feed into common and/or federated resources such as the Gene Ontology, Synaptic Gene Ontology, and FAIR-aligned data informatics ecosystems. The broader objective is to help close a persistent gap in neuroscience and psychiatry research: moving from statistical or observational links between risk factors and disorders to specific mechanisms and testable targets for intervention.

This is an R21 mechanism, which is designed for high-risk, high-reward exploratory projects, including proof-of-concept efforts where there is little or no preliminary data. Projects that already have feasibility well established are directed to apply instead to the companion R01 opportunity (referenced in the NOFO), which is better suited to more mature research programs.

Eligibility is broad and includes many organization types across the public, private, and nonprofit spectrum. Eligible applicants include state, county, city/township, and special district governments; public and state-controlled and private institutions of higher education; independent school districts; Native American tribal governments (federally recognized) and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses) and small businesses; and other categories. The NOFO also explicitly notes additional eligible applicant groups such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISI institutions, Hispanic-serving institutions, HBCUs, tribally controlled colleges and universities, faith-based or community-based organizations, regional organizations, eligible federal agencies, non-U.S. entities (foreign organizations), tribal governments that are not federally recognized, and U.S. territories or possessions. The sponsoring agency is the National Institutes of Health, the opportunity was created on 2024-11-18, and the listed original closing date is 2026-09-07. The award ceiling and expected number of awards are not specified in the provided source information.

• 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 2024-11-18.
• 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 25 037

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