Advancing Research to Understand Congenital Malformations (R01 Clinical Trial Not Allowed) | PAR 22 215

Opportunity Information: Apply for PAR 22 215

The National Institutes of Health (NIH) is offering an R01 grant opportunity titled "Advancing Research to Understand Congenital Malformations (R01 Clinical Trial Not Allowed)" under funding opportunity number PAR-22-215. The central goal of this program is to fund innovative, mechanistic research that explains how structural birth defects (congenital malformations) form. A key emphasis is on integrating animal model research with human translational and clinical approaches so that discoveries about basic developmental mechanisms can be connected back to real-world patterns of risk, susceptibility, and variation seen in human populations.

This FOA is aimed at studies that dig into the biological and developmental pathways that lead to structural malformations, including why certain individuals or populations may be more susceptible than others and why the same exposure or genetic change can produce different outcomes. The NIH is specifically encouraging applicants to use modern tools and experimental strategies that can clarify causal mechanisms rather than simply describing associations. This includes leveraging advances in genetics and high-throughput "omics" approaches such as genomics, proteomics, and metabolomics, as well as epigenetic profiling and related systems-level measurements. The announcement also highlights synthetic biology, biochemical methods, and other developmental biology approaches, signaling interest in projects that can manipulate, model, or reconstruct pathways to determine how specific disruptions lead to malformations.

A major scientific theme in the announcement is the identification and characterization of factors that contribute to congenital malformations, including genetic variants, epigenetic alterations, environmental influences, and gene-by-environment interactions. In practice, that can include work that traces how a genetic mutation changes a developmental program, how an environmental exposure alters signaling or tissue patterning, or how combined genetic and environmental factors interact to shift risk. The program’s emphasis on animal models, paired with human translational/clinical work, suggests NIH is looking for proposals that can use controlled model systems to test mechanisms while also grounding the work in human biology, human-relevant exposures, or clinically observed phenotypes.

The opportunity uses the NIH R01 mechanism, meaning it is intended for substantial, hypothesis-driven research projects with clearly defined aims and a coherent plan to produce meaningful advances in understanding. It is explicitly labeled "Clinical Trial Not Allowed," which means applications should not propose clinical trials as part of the project. In general terms, that typically steers applicants toward mechanistic, observational, or preclinical translational research rather than interventional studies that prospectively assign human participants to interventions.

This is a discretionary grant program in the Health, Income Security and Social Services category and is listed under CFDA number 93.865. The agency is NIH, and the opportunity was created on 2022-08-09. The original closing date provided is 2025-09-07. The listing shows an award ceiling of $499,999, indicating the maximum amount shown for an award under this announcement (applicants should still pay attention to NIH budget rules and any institute-specific guidance when preparing budgets).

Eligibility is broad and includes many types of U.S.-based organizations and governmental units, such as state, county, and city governments; special district governments; independent school districts; and federally recognized Native American tribal governments. Higher education institutions are eligible, including public/state-controlled and private institutions of higher education. Nonprofit organizations are eligible both with and without 501(c)(3) status, provided they are not institutions of higher education (since universities are already covered as a separate category). The FOA also allows applications from for-profit organizations (other than small businesses) and from small businesses, as well as additional eligible applicant categories labeled as "Others."

In addition to the standard eligibility groups, the FOA explicitly calls out several categories of institutions and organizations as other eligible applicants. These include Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISISs); Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); and Indian/Native American Tribal Governments that are not federally recognized. It also includes eligible agencies of the federal government, faith-based or community-based organizations, U.S. territories or possessions, and regional organizations. Notably, the announcement also lists non-domestic (non-U.S.) entities (foreign organizations) as eligible, which can be important for research teams with specialized expertise, unique model systems, or access to distinctive populations or resources outside the United States.

Overall, this funding opportunity is best understood as NIH support for cutting-edge, mechanistic congenital malformation research that connects rigorous experimental work in animal and other model systems with human-relevant translational evidence. Competitive projects will likely be those that use modern genetic and multi-omics tools to pinpoint causes and pathways, explain variability in outcomes, and clarify how genes and environments interact during development to produce structural birth defects, all while staying within the "no clinical trial" boundary.

• 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 2022-08-09.
• 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.)
• Each selected applicant is eligible to receive up to $499,999.00 in funding.
• 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 22 215

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