Pilot Projects Investigating Understudied Proteins Associated with Rare Diseases (R03 Clinical Trial Not Allowed) | PAR 25 122

FAQs: NIH PAR-25-122 - Pilot Projects Investigating Understudied Proteins Associated with Rare Diseases (R03 Clinical Trial Not Allowed)

What is this funding opportunity (PAR-25-122) trying to support?

This NIH discretionary grant program supports early-stage, tightly scoped pilot studies focused on "understudied proteins" that have known links to rare diseases but remain poorly characterized. The goal is to generate practical first-step evidence and/or enabling tools that make deeper future research possible, such as preliminary data, assays, reagents, or proof-of-concept findings.

What is the central scientific aim of the program?

The central aim is to help researchers determine what eligible understudied proteins do, how they fit into rare disease biology, how they contribute to disease mechanisms, and why they may matter as potential therapeutic targets. The emphasis is on foundational biochemical and biological understanding rather than large translational programs.

What kinds of proteins must applicants work on?

Applicants must work on an eligible set of "understudied proteins" provided by the program. These proteins are described as belonging to druggable protein families and having known associations with rare diseases, but they have not been studied enough to clearly define biochemical function, biological role, or disease relevance.

Can applicants propose work on any rare-disease protein of their choosing?

No. A defining feature is that the project must focus on an eligible set of understudied proteins provided by the program, rather than any protein selected solely by the applicant.

What research stage is NIH trying to fund here?

This opportunity is positioned as a jumpstart mechanism. It is meant to fund the "first-mile" work: focused pilot studies that produce preliminary data and/or enabling tools that make subsequent, deeper investigations feasible (including future R01-level work).

What types of studies are most aligned with the NOFO?

The NOFO emphasizes basic biochemical and/or biological work that clarifies function, pathways, interactions, and disease context. Examples described include molecular characterization, cell-based functional studies, biochemical assays, pathway mapping, genetic perturbation experiments, and development of experimental platforms that illuminate protein function in a rare disease setting.

Is this opportunity intended for large, multi-year translational programs?

No. The R03 mechanism and the stated purpose indicate this is intended for smaller, time-limited pilot efforts that deliver concrete, early outputs rather than large-scale translational programs.

What is the maximum award amount?

The listed award ceiling is $100,000. This reinforces that projects should be tightly scoped and designed to deliver clear outputs such as preliminary experimental validation or tool/assay development.

What does "R03" mean in practice for project scope?

Because this is an R03 mechanism, it is structured to support smaller, time-limited pilot studies. The intent is to fund focused projects that can quickly generate enabling data or tools that position the field for larger future investigations.

Are clinical trials allowed under this NOFO?

No. This opportunity is explicitly labeled "Clinical Trial Not Allowed." The supported research should not involve the prospective assignment of human participants to interventions to assess health-related outcomes.

If clinical trials are not allowed, what kind of human-related research (if any) is implied?

Based on the information provided, the intended work stays in the preclinical and foundational research space. The NOFO description emphasizes biochemical and biological studies and tool development rather than clinical testing of interventions.

What kinds of outputs is NIH expecting from these pilot projects?

The program is designed to produce concrete deliverables that enable future research. Examples highlighted include preliminary data, early experimental validation, proof-of-concept findings, assay development, reagents, and other tools that help clarify protein function and disease relevance.

Why is NIH focusing on "understudied proteins" in rare diseases?

The NOFO targets a common gap: many disease-associated genes and proteins are known from databases and genetic studies, but they often lack the foundational experimental evidence needed to define function and mechanism. NIH is aiming to close that gap so these proteins become more tractable for broader research and drug discovery.

Who is eligible to apply?

The opportunity is broadly open to many U.S. applicant organization types, including domestic public-sector entities (such as state, county, city or township governments; special district governments; independent school districts), higher education institutions (public/state-controlled and private), federally recognized tribal governments and tribal organizations, public housing authorities/Indian housing authorities, nonprofit organizations (with or without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and other eligible applicant types. Eligible federal agencies are also included among eligible applicants.

Are minority-serving institutions specifically included as eligible applicants?

Yes. The NOFO highlights that categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs) are eligible or included among eligible applicants.

Are faith-based or community-based organizations eligible?

Yes. The NOFO explicitly notes faith-based or community-based organizations among eligible or included applicant categories.

Can a foreign (non-U.S.) organization apply as the primary applicant?

No. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply as applicant institutions, and non-domestic components of U.S. organizations are also not eligible to apply.

Are any foreign activities allowed at all?

Yes. Although a foreign organization cannot be the primary applicant, the NOFO allows foreign components as defined by the NIH Grants Policy Statement. This means a U.S.-based applicant may be able to include certain justified and compliant foreign elements (such as specific collaborations, resources, or activities conducted abroad) as part of the project.

Which agency is running this opportunity?

The opportunity is run by the National Institutes of Health (NIH) and falls under health-related funding activity categories.

What CFDA numbers are associated with this listing?

The listing includes CFDA numbers 93.121, 93.173, 93.242, 93.350, 93.853, and 93.855.

When was this opportunity created, and what is the closing date?

The opportunity was created on 2024-10-28, and the original closing date is 2027-11-16, providing a multi-year window for planning and submission under this announcement.

Does the listing state how many awards NIH expects to make?

No. The information provided does not specify the number of expected awards. It does indicate an intent to seed multiple pilot projects to expand knowledge around these neglected, disease-linked proteins.

What is the big-picture purpose of this NOFO for the rare disease community?

It is targeted seed funding for rigorous early experimental work that makes rare-disease-associated but poorly understood proteins more usable to the research and drug discovery ecosystem. The longer-term goal is to enable stronger future applications and accelerate progress toward therapies by establishing functional and biological credibility for these proteins.