Model Organisms Screening Center for the Undiagnosed Diseases Network (UDN) Phase II (U54) | RFA RM 17 017

Opportunity Information: Apply for RFA RM 17 017

The funding opportunity titled "Model Organisms Screening Center for the Undiagnosed Diseases Network (UDN) Phase II (U54)" is a National Institutes of Health (NIH) initiative designed to strengthen the Undiagnosed Diseases Network by adding a dedicated center focused on rapid functional testing of candidate disease-causing gene variants. Issued as RFA-RM-17-017, this award uses the cooperative agreement mechanism (U54), which generally means the NIH expects to have substantial involvement in coordinating activities, milestones, and network integration rather than simply providing funds with minimal oversight. The program sits within the NIH Common Fund (CFDA 93.310), reflecting its cross-cutting, high-impact intent and its role in accelerating discoveries that can affect many areas of medicine, not just one disease category.

At its core, the grant supports the establishment and operation of a Model Organisms Screening Center for Phase II of the UDN. The Center is expected to evaluate the pathogenicity (whether a variant is actually disease-causing) and biological function of roughly 200 gene variants each year that have been identified through UDN clinical and genomic investigations. This is important because sequencing often finds rare or novel variants that look suspicious but cannot be confidently linked to a patient’s condition without functional evidence. The Center’s job is to close that gap by creating a reliable, scalable pipeline that can move from a prioritized variant list to experimental results that help interpret clinical significance and illuminate disease mechanisms.

Applications are expected to propose a clear screening strategy that explains how the Center will choose the most informative variants to study from among those emerging from the UDN. Since functional testing capacity is finite, the FOA emphasizes the need for rational selection and triage approaches, such as prioritizing variants based on phenotype match, predicted impact on protein function, gene constraint metrics, inheritance patterns, or the feasibility of modeling the variant in experimental systems. The FOA also makes it clear that the funded Center should not be a single-assay operation; it should be a platform with a defined pipeline that can handle volume, support decision-making, and produce interpretable results that feed back into UDN case resolution.

A major requirement is that the research platform include, at minimum, both Drosophila (fruit fly) and zebrafish models. These organisms are widely used in human disease research because they offer complementary strengths: Drosophila enables rapid genetics, powerful variant manipulation, and efficient screening in a living organism, while zebrafish provides a vertebrate context with strong developmental and organ-system relevance, including imaging-friendly embryology that can be valuable for modeling congenital and neurologic phenotypes. The FOA allows, and implicitly encourages when justified, adding other small animal models or cell-based assays to strengthen the pipeline. This could include organisms like C. elegans or mouse for specific questions, as well as in vitro approaches such as patient-derived cells, iPSC-based systems, organoids, or targeted biochemical assays. The guiding principle is that the chosen models and assays should be appropriate for evaluating gene function in a way that maps onto the UDN participant’s disease phenotype, rather than producing generic molecular readouts that are hard to interpret clinically.

The practical expectation is that the Center will operate as a functional genomics hub for the UDN, translating genetic findings into biological and clinically meaningful evidence. For each selected variant, the Center would typically develop or apply assays that test whether the variant disrupts gene function, alters relevant pathways, or reproduces aspects of the patient’s phenotype in the model system. Results from these studies can help reclassify variants of uncertain significance, support diagnoses for rare disease patients, identify new gene-disease relationships, and generate mechanistic insights that might guide future therapeutic research. Because this is framed as a network resource, the work is meant to be systematic and service-oriented in addition to being scientifically rigorous, with an emphasis on throughput, standardization, and timely communication back to the UDN.

In terms of applicant eligibility, the opportunity is broadly open across many domestic organization types, including state, county, and municipal governments; public and state-controlled institutions of higher education; private institutions of higher education; independent school districts; special district governments; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations other than small businesses; and small businesses. The FOA explicitly highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, faith-based or community-based organizations, Hispanic-serving institutions, historically Black colleges and universities, tribally controlled colleges and universities, regional organizations, eligible federal agencies, and U.S. territories or possessions. At the same time, it draws firm boundaries around non-U.S. applicants: non-domestic (non-U.S.) entities and non-domestic components of U.S. organizations are not eligible to apply. However, foreign components, as NIH defines them in the NIH Grants Policy Statement, are allowed, meaning a U.S.-based awardee can include certain international collaborations or activities as components of the project if they meet NIH requirements and are well justified.

Administratively, the FOA was created on August 15, 2017, and the original closing date listed is November 2, 2017. The listing does not specify an award ceiling or the number of expected awards in the provided text, but the intent is clearly to fund a center-level capability rather than small, disconnected projects. Overall, this opportunity is aimed at building an integrated, high-throughput functional testing pipeline anchored in model organism biology, tightly coupled to UDN clinical cases, and structured to generate actionable evidence about whether and how rare gene variants contribute to human disease.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Model Organisms Screening Center for the Undiagnosed Diseases Network (UDN) Phase II (U54)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.310.
• This funding opportunity was created on 2017-08-15.
• Applicants must submit their applications by 2017-11-02. (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 RFA RM 17 017

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: