Knockout Mouse Phenotyping (U54) | Apply Online

Opportunity Summary:

The Knockout Mouse Phenotyping (U54) funding opportunity (RFA-RM-10-011) is a National Institutes of Health (NIH) cooperative agreement that supports large-scale, standardized phenotyping of mutant mouse lines produced by the International Knockout Mouse Consortium (IKMC). The central goal is to generate functional information for every protein-coding gene in the mammalian genome by observing what changes when each gene is knocked out. In practical terms, the program is meant to turn engineered mouse mutants into broadly useful biological insight by applying comprehensive, systematic testing so researchers can connect specific genes to measurable traits, diseases, or biological pathways.

This opportunity is administered through the Office of Strategic Coordination within the NIH Office of the Director and uses the U54 mechanism, meaning it is designed for complex, multi-component projects carried out in close coordination with NIH staff. Because it is a cooperative agreement rather than a standard research project grant, awardees should expect substantial NIH involvement in shaping priorities, ensuring harmonized methods, coordinating across sites, and emphasizing production-style throughput, data quality, and consistent reporting. The FOA also runs in parallel with related solicitations using U54 and U42 mechanisms (RFA-RM-10-012 and RFA-RM-10-013), signaling a broader coordinated initiative where different awards may cover complementary roles such as phenotyping operations, data handling, and distribution or resource-related functions.

The scope of work centers on "broad phenotyping," which typically implies a wide panel of assays rather than narrow, hypothesis-driven experiments. The intent is to capture diverse physiological and behavioral readouts across major organ systems and biological functions so that gene-to-phenotype relationships can be discovered even when no prior hypothesis exists. This kind of systematic phenotyping is especially valuable for genes with unknown function, subtle effects, pleiotropic impacts across multiple systems, or relevance to complex human disease. The expected outputs are datasets and associated interpretations that the wider biomedical research community can use to guide deeper mechanistic studies, identify candidate disease genes, and prioritize therapeutic targets.

Funding levels are sized for substantial, programmatic operations. Applicants may request up to $7.4 million per year in total costs for project periods of up to five years, and NIH anticipated making between 2 and 4 awards, contingent on the scientific merit of applications. The estimated total funding across the initiative is listed as $37 million. There is no cost-sharing or matching requirement, which reduces barriers for institutions that can operate high-throughput phenotyping pipelines but may not be able to contribute non-federal matching funds.

Eligibility is broad and includes many types of organizations: public and private institutions of higher education, nonprofit organizations with or without 501(c)(3) status (other than institutions of higher education), small businesses, for-profit organizations (other than small businesses), state governments, and certain other entities described in the announcement. The eligibility language also explicitly includes several categories of institutions and agencies often highlighted for federal programs, 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 eligible federal agencies. This reflects an intent to attract capable operational centers and consortia regardless of sector, so long as they can meet the technical, logistical, and collaborative demands of standardized mouse phenotyping at scale.

Administratively, the opportunity was posted on September 10, 2010, with an original and current closing date of November 10, 2010, and an archive date of December 11, 2010. The funding instrument type is listed as a cooperative agreement, and the activity category spans education, health, income security, and social services, consistent with NIH-wide, cross-cutting biomedical research infrastructure programs. Multiple CFDA numbers are associated with the announcement, reflecting the trans-NIH relevance of knockout phenotyping to many disease and research areas, including cancer biology, cardiovascular and lung diseases, neurological disorders, mental health, aging, vision, musculoskeletal disease, substance use, sleep, and human genome research, among others.

Overall, this FOA is best understood as an NIH-supported, consortium-style effort to industrialize the process of discovering gene function using knockout mice. Successful applicants would be expected to operate as high-capacity phenotyping centers that can process IKMC mutant lines efficiently, generate rigorous and comparable phenotype data, and contribute to a shared objective: building a functional atlas linking mammalian genes to biological outcomes in ways that accelerate basic discovery and translational research.

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Previous opportunity: Knockout Mouse Phenotyping Project Database (U54)

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