Encouraging Development of Novel Amelogenesis Models (UG3/UH3 Clinical Trial Not Allowed) | RFA DE 19 004

Opportunity Information: Apply for RFA DE 19 004

The National Institutes of Health (NIH) funding opportunity titled "Encouraging Development of Novel Amelogenesis Models (UG3/UH3 Clinical Trial Not Allowed)" (RFA-DE-19-004; CFDA 93.121) is designed to push the field of tooth enamel research forward by supporting the creation and validation of better, more physiologically realistic models of amelogenesis. Amelogenesis is the process by which enamel is formed and matured, and the FOA is focused on improving the research tools needed to study both normal enamel development and enamel-related diseases in humans. The central idea is that progress in understanding enamel formation and pathology has been limited by model systems that do not adequately mirror real human biology, so this program aims to fund models that are more faithful to human physiology and more useful for translational research.

The FOA lays out two main scientific objectives that applicants are expected to address in tandem. First, projects should generate new or significantly improved models that closely mimic how enamel develops and matures under physiological conditions. That can include models that capture relevant cellular behavior (such as ameloblast differentiation and function), tissue architecture, mineralization dynamics, and the biological environment that supports enamel formation. Second, the FOA emphasizes validation: it is not enough to build a model that looks promising on paper. The model must be tested and benchmarked to demonstrate that it is robust, reproducible, and accurately reflects key aspects of human enamel biology, including meaningful representation of disease or pathological states when applicable. The overall expectation is that these validated models will become enabling resources that other researchers can rely on to investigate multiscale processes of enamel formation, from molecular events to tissue-level outcomes, and ultimately to inform strategies that prevent, mitigate, or treat conditions affecting enamel and related oral structures.

This program uses the NIH Exploratory/Developmental Phased Award Cooperative Agreement mechanism (UG3/UH3), which is structured to support high-impact development work while enforcing clear go/no-go decision points. In the UG3 phase, teams carry out the early development and proof-of-concept work through a milestone-driven plan. Those milestones are reviewed to determine whether the project is meeting predefined performance and validation targets. Only projects that successfully achieve the UG3 milestones are eligible to transition to the UH3 phase, which provides continued support to further advance, scale, and solidify the outcomes from the UG3 stage. Because this is a cooperative agreement, NIH involvement is typically more substantial than in a standard grant, with a greater emphasis on coordination, milestone tracking, and programmatic oversight. The FOA also states "Clinical Trial Not Allowed," meaning the supported work must not include clinical trials as defined by NIH; the focus is on model development and validation rather than testing interventions in human trial settings.

In terms of who can apply, the eligibility is broad and includes many types of U.S.-based organizations and governmental entities. Eligible applicants include state, county, city or township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; other Native American tribal organizations; public housing authorities and Indian housing authorities; nonprofit organizations with or without 501(c)(3) status (other than higher education institutions); for-profit organizations (other than small businesses); and small businesses. The FOA also explicitly highlights additional eligible groups such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions.

The FOA includes important constraints related to foreign participation. Non-domestic (non-U.S.) entities, including foreign organizations and foreign institutions, are not eligible to apply as the primary applicant. Non-domestic components of U.S. organizations are also not eligible to apply. However, foreign components are allowed under NIH policy, meaning a U.S.-based applicant organization may include certain foreign elements or collaborations if they meet NIH definitions and requirements for a foreign component. This distinction matters for teams that want to incorporate specialized expertise, data, or capabilities located outside the United States while still keeping the applicant institution domestic.

From an administrative and funding snapshot perspective, the opportunity is categorized as discretionary and uses the cooperative agreement funding instrument within the health activity category. The source data lists an award ceiling of $400,000, a creation date of July 11, 2018, and an original closing date of October 4, 2018. While the listing shows "ExpectedAwards:" without a populated number, the key takeaway is that awards are intended to support milestone-based development and subsequent validation and advancement, rather than open-ended exploratory work without defined performance checks.

Overall, this FOA is aiming to strengthen the foundation of enamel research by funding model systems that the community can trust. By insisting on both innovation (new or improved amelogenesis models) and rigorous validation (proof that the models are robust and representative of human biology), and by using a phased UG3/UH3 structure with milestone-driven progression, NIH is signaling that it wants deliverables that can reliably accelerate research on enamel development and enamel-associated disease mechanisms.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Encouraging Development of Novel Amelogenesis Models (UG3/UH3 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): 93.121.
• This funding opportunity was created on 2018-07-11.
• Applicants must submit their applications by 2018-10-04. (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 $400,000.00 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 RFA DE 19 004

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