Advancing Research to Understand Congenital Malformations (R01 Clinical Trial Not Allowed) | PAR 25 146

Opportunity Information: Apply for PAR 25 146

The National Institutes of Health (NIH) is soliciting applications for the grant opportunity "Advancing Research to Understand Congenital Malformations (R01 Clinical Trial Not Allowed)" (Funding Opportunity Number: PAR-25-146; CFDA: 93.865). This is a discretionary research grant using the NIH R01 mechanism, focused specifically on improving scientific understanding of how structural birth defects (congenital malformations) form. The central goal is to support innovative, mechanistic research that connects findings from animal model systems with human translational and clinical observations, so that discoveries in developmental biology can more directly explain risk, susceptibility, and variability seen in human populations.

The NOFO emphasizes projects that investigate the biological mechanisms behind structural birth defects by integrating animal models with human-relevant data or approaches. NIH is encouraging applicants to leverage major advances in genetics and high-throughput "omics" and systems-level tools, including genomics, proteomics, metabolomics, and related methods. In addition, the opportunity highlights the value of synthetic biology, biochemical strategies, and other developmental biology approaches that can pinpoint causal pathways and test hypotheses about early development. A strong application under this NOFO would typically move beyond describing an association and instead aim to clarify how specific factors alter developmental processes in a way that leads to malformations.

A key priority is identifying and characterizing factors that contribute to the formation of congenital malformations, including genetic variants, epigenetic modifications, environmental exposures, and gene-by-environment interactions. The NOFO is also interested in research that helps explain why some individuals are more susceptible than others, and why the same condition can vary in severity or presentation across different people. In practice, this could include studies that map molecular pathways disrupted during development, examine how exposures influence gene regulation during critical windows, or use multi-omics data to connect molecular changes to anatomical outcomes, while grounding those findings in human translational relevance.

This opportunity is explicitly labeled "Clinical Trial Not Allowed," meaning the proposed research cannot include a clinical trial as defined by NIH (for example, prospective assignment of human participants to an intervention to evaluate effects on health-related biomedical outcomes). The intent is to fund mechanistic and translational research rather than interventional clinical studies, so applicants should design human components accordingly, such as analyses of existing clinical data, biospecimen-based translational work, observational or natural-history research that does not meet the NIH definition of a clinical trial, and other human-relevant approaches that complement animal-model experimentation.

Eligibility is broad and includes many types of U.S. and non-U.S. organizations. Eligible applicants include state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; nonprofits with or without 501(c)(3) status (other than institutions of higher education); public housing authorities/Indian housing authorities; for-profit organizations other than small businesses; small businesses; and federally recognized Native American tribal governments. The NOFO also calls out additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISI); Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); Indian/Native American tribal governments that are not federally recognized; faith-based or community-based organizations; eligible federal agencies; regional organizations; non-domestic (non-U.S.) entities (foreign organizations); and U.S. territories or possessions. In short, NIH is aiming for wide participation across academic, nonprofit, governmental, community-based, and international research environments.

Key administrative details provided include an original closing date of 2025-09-07, with the opportunity first created on 2024-11-06. The award ceiling and expected number of awards are not specified in the provided source data, which typically means applicants should consult the full NOFO text in NIH systems for budget guidance, project period expectations, and any institute- or program-specific constraints.

Overall, this NOFO is geared toward R01-level, hypothesis-driven research that uses modern genetic and molecular toolkits to uncover how congenital malformations arise, with an explicit expectation that investigators will connect animal-model insights to human biology in a translationally meaningful way, while avoiding study designs that constitute a clinical trial.

• The National Institutes of Health in the health, income security and social services sector is offering a public funding opportunity titled "Advancing Research to Understand Congenital Malformations (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): 93.865.
• This funding opportunity was created on 2024-11-06.
• Applicants must submit their applications by 2025-09-07. (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 25 146

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