Cellular and Molecular Biology of Complex Brain Disorders (R01 Clinical Trial Not Allowed) | PAR 25 038

Opportunity Information: Apply for PAR 25 038

The National Institutes of Health funding opportunity PAR-25-038, titled "Cellular and Molecular Biology of Complex Brain Disorders (R01 Clinical Trial Not Allowed)," supports research that digs into how well-supported (high-confidence) risk factors for complex brain disorders actually affect neural function at the level of cells, connections between cells, and brain circuits. Here, "complex" is meant broadly: it can refer to disorders where risk is shaped by many factors at once (such as combinations of multiple genes and/or environmental exposures), and it can also refer to conditions where the relevant brain functions are distributed across many regions and circuit elements rather than localized to one spot. The core idea is to move from knowing that a risk factor is associated with a disorder to understanding what it does biologically and mechanistically in the nervous system.

Projects can be either discovery-oriented (hypothesis-generating, including unbiased approaches) or more targeted (hypothesis-testing). NIH is open to a wide range of experimental systems as long as they are suited to clarifying mechanism, including in vivo work in model organisms, in situ approaches in intact tissues, and in vitro experiments such as human cell-based assays. Behavioral tasks and behavioral outcome measures may be included if they help connect molecular and cellular findings to circuit-level function, but the announcement is explicit that behavior is not required and not the central expectation. The emphasis stays on intracellular processes (what happens inside neurons and glia), transcellular processes (how cells interact and communicate, including synaptic and non-synaptic signaling), and circuit substrates (how ensembles and connections give rise to functional properties relevant to disease risk).

A key boundary in this NOFO is that applicants should not frame the work as "modeling" a disorder in a broad, end-to-end way. Instead, the work should isolate and explain the neurobiological impact of one or more specific risk factors. That can mean identifying which molecular or cellular components are affected, mapping how those components relate to each other within a defined biological process, and clarifying the chain of events that links a risk factor to changes in neural function. NIH also signals that studying fundamental biology is appropriate when it directly improves understanding of risk factor mechanisms, meaning a project can focus on basic pathways, cellular machinery, or circuit operations that are altered by risk-associated genes or exposures.

Another major goal is broad usability and dissemination of what is learned. The opportunity stresses that resulting experimental paradigms, component pathways, and defined biological processes should be shared with enough structure and detail that they can strengthen common or federated data resources. Examples named include the Gene Ontology, Synaptic Gene Ontology, and FAIR-oriented informatics resources. In practical terms, NIH is pushing applicants to describe mechanisms in ways that can be standardized, compared across studies, and integrated into shared knowledge frameworks, so the field can better connect risk factors to mechanisms and, ultimately, to therapeutic target identification.

Mechanistically, this is an R01, which is positioned for projects where feasibility or proof-of-concept has already been established and the next step is deeper, more complete development of an existing line of inquiry. Applicants who are still at an early, conceptual, or exploratory stage are directed to a companion R21 announcement (PAR-24-025) rather than using this R01. As stated in the title, clinical trials are not allowed under this NOFO, so proposed human studies need to stay on the mechanistic, non-interventional side (for example, cellular assays or observational analyses tied to experimental biology, rather than testing interventions in participants).

Eligibility is broad and includes many organization types: public and private institutions of higher education, nonprofits (with or without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and various units of government (state, county, city/township, special districts, independent school districts), plus tribal governments and tribal organizations. The NOFO also explicitly highlights additional eligible applicants 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, U.S. territories or possessions, and non-U.S. entities (foreign organizations), among others. The opportunity is administered by NIH under CFDA 93.242. The original closing date listed is 2026-09-07. The public synopsis does not specify an award ceiling or expected number of awards.

Overall, PAR-25-038 is aimed at sharpening the mechanistic bridge between credible brain-disorder risk factors and the cellular, molecular, and circuit-level biology they perturb, while also pushing the field toward standardized, shareable representations of those mechanisms that can accelerate target discovery and cumulative progress across labs and datasets.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Cellular and Molecular Biology of Complex Brain Disorders (R01 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 25 038

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