Opportunity Information: Apply for RFA RM 15 017

The NIH Common Fund funding opportunity titled "Limited Competition: Knockout Mouse Production and Phenotyping Project (UM1)" (RFA-RM-15-017) supports a large, coordinated effort under the Knockout Mouse Phenotyping Program (KOMP2) to systematically generate and characterize null-mutant (gene knockout) mouse lines. The central aim is to build a comprehensive, standardized phenotype resource for essentially every protein-coding gene in the mammalian genome, using the widely adopted C57BL/6 mouse strain as the reference background. By creating knockouts and documenting what changes in biology and disease-relevant traits occur when each gene is disabled, the program is designed to accelerate functional genomics and improve the interpretation of human genetic variation by providing experimentally grounded gene-function evidence.

This announcement uses a UM1 cooperative agreement mechanism, meaning NIH expects substantial programmatic involvement and coordination rather than a typical investigator-initiated grant with minimal federal steering. The work is framed as high-impact, cross-cutting infrastructure science consistent with the Common Fund's mission: enabling bold approaches that can rapidly move a field forward and produce broadly usable community resources. In practical terms, the funded projects are expected to operate at high throughput and to prioritize reproducibility, standard operating procedures, and systematic data sharing so the outputs can be used immediately by many different biomedical research groups.

The specific project objectives are end-to-end production and dissemination of knockout mouse resources. Applicants are expected to: (1) generate mutant mouse lines using CRISPR/Cas9 genome editing, targeting the creation of null alleles; (2) run broad-based phenotyping pipelines to measure physiological, anatomical, behavioral, and other traits in a standardized way; (3) conduct rigorous quality control to confirm the intended genetic edits and to ensure the integrity of the lines and resulting datasets; (4) cryopreserve germplasm (such as sperm and/or embryos) to secure the lines for long-term distribution and reproducibility; and (5) make both the mice and the associated phenotype and QC data readily accessible to the broader scientific community. The intent is not just to create individual models, but to create a scalable platform that continuously produces validated knockouts plus high-value, comparable phenotype readouts.

The FOA sets an explicit throughput expectation: approximately 600 null-mutant lines phenotyped per year, totaling about 3,000 lines over a five-year project period. This scale emphasizes industrialized workflows, careful scheduling, and consistent assay performance across time, along with informatics practices capable of handling large volumes of standardized data. The mouse model is highlighted as particularly suitable for this kind of systematic functional genomics because of decades of genetic knowledge, mature reproductive and colony-management technologies, relatively short generation times, and lower costs compared with other mammalian systems. The announcement also reflects the shift in feasibility driven by CRISPR/Cas9, which significantly reduces time and cost for producing targeted mutations and enables the kind of comprehensive genome-wide knockout effort envisioned here.

Eligibility is limited to U.S.-based higher education institutions, including public/state-controlled and private institutions of higher education. Foreign (non-U.S.) institutions are not eligible to apply, and non-domestic components of U.S. organizations are not eligible to apply, though foreign components as defined in the NIH Grants Policy Statement are allowed. The opportunity is categorized as discretionary funding and is administered by the National Institutes of Health. Key administrative details provided include an original closing date of December 9, 2015, and a creation date of October 7, 2015. The program is associated with multiple CFDA numbers (including 93.113, 93.121, 93.172, 93.173, and others), reflecting the Common Fund's cross-institute, cross-disease scope and its emphasis on broadly enabling biomedical research rather than focusing on a single disease area.

  • The National Institutes of Health in the education, environment, food and nutrition, health, income security and social services sector is offering a public funding opportunity titled "Limited Competition: Knockout Mouse Production and Phenotyping Project (UM1)" and is now available to receive applicants.
  • Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.113, 93.121, 93.172, 93.173, 93.233, 93.273, 93.279, 93.310, 93.313, 93.351, 93.396, 93.837, 93.838, 93.839, 93.846, 93.847, 93.853, 93.855, 93.856, 93.865, 93.866, 93.867.
  • This funding opportunity was created on 2015-10-07.
  • Applicants must submit their applications by 2015-12-09. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
  • Eligible applicants include: Public and State controlled institutions of higher education, Private institutions of higher education.
Apply for RFA RM 15 017

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Frequently Asked Questions (FAQs)

What is the title of this NIH funding opportunity?

The funding opportunity is titled "Limited Competition: Knockout Mouse Production and Phenotyping Project (UM1)" (RFA-RM-15-017).

Which NIH program is this opportunity associated with?

This opportunity supports work under the Knockout Mouse Phenotyping Program (KOMP2), a coordinated effort to generate and characterize null-mutant (gene knockout) mouse lines.

What is the main purpose of this project?

The central purpose is to build a comprehensive, standardized phenotype resource for essentially every protein-coding gene in the mammalian genome by systematically disabling genes (creating null mutants) and measuring resulting biological and disease-relevant trait changes.

Why does NIH consider this a high-impact, cross-cutting effort?

The project is framed as infrastructure science aligned with the NIH Common Fund mission: producing broadly usable community resources, using standardized methods, and enabling rapid field-wide progress by making outputs immediately useful across many biomedical research areas.

What grant mechanism is used for this announcement?

The FOA uses a UM1 cooperative agreement mechanism.

What does a UM1 cooperative agreement imply about NIH involvement?

A UM1 cooperative agreement indicates NIH expects substantial programmatic involvement and coordination, rather than the lighter federal role typical of many investigator-initiated grants.

What organism and strain are specified as the reference background?

The program uses the widely adopted C57BL/6 mouse strain as the reference genetic background for generating and phenotyping the knockout lines.

What type of mutations are applicants expected to create?

Applicants are expected to generate null alleles (gene knockouts) so that each targeted gene is disabled, enabling assessment of phenotypic consequences.

What genome editing approach is specifically called out?

The FOA specifies the use of CRISPR/Cas9 genome editing to generate mutant mouse lines targeting null alleles.

What are the required end-to-end project components described in the FOA?

The described objectives include: (1) generating mutant mouse lines using CRISPR/Cas9 targeting null alleles; (2) running broad-based, standardized phenotyping pipelines; (3) conducting rigorous quality control (QC) to confirm genetic edits and ensure line/data integrity; (4) cryopreserving germplasm (such as sperm and/or embryos) for long-term security and reproducibility; and (5) making mice and associated phenotype/QC data readily accessible to the broader scientific community.

What kinds of phenotyping are expected?

The FOA describes broad-based phenotyping pipelines that measure physiological, anatomical, behavioral, and other traits in a standardized way.

What quality control expectations are included?

Projects are expected to perform rigorous QC to confirm the intended genetic edits and to ensure the integrity of mouse lines and the resulting datasets.

What does the FOA say about cryopreservation?

The FOA expects cryopreservation of germplasm (for example, sperm and/or embryos) to secure the lines for long-term distribution and reproducibility.

What are the expectations for sharing resources and data?

The intent is for both the mice and the associated phenotype and QC data to be made readily accessible to the broader scientific community, emphasizing systematic data sharing and immediate usability.

Is the goal to create a few specific mouse models or something broader?

The FOA emphasizes building a scalable platform that continuously produces validated knockout lines along with high-value, comparable phenotype readouts, rather than producing only isolated individual models.

What throughput does the FOA explicitly expect?

The FOA sets an expectation of approximately 600 null-mutant lines phenotyped per year.

How many total null-mutant lines are expected over the full project period?

The FOA indicates a total of about 3,000 null-mutant lines over a five-year project period.

What does the stated throughput imply about how projects should operate?

The scale implies high-throughput, industrialized workflows; careful scheduling; consistent assay performance over time; and informatics practices capable of handling large volumes of standardized phenotype and QC data.

Why is the mouse model highlighted as suitable for this program?

The FOA notes the mouse is well-suited for systematic functional genomics due to decades of genetic knowledge, mature reproductive and colony-management technologies, relatively short generation times, and lower costs compared with other mammalian systems.

How does CRISPR/Cas9 affect feasibility for this effort?

The FOA reflects that CRISPR/Cas9 substantially reduces time and cost for producing targeted mutations, enabling a comprehensive genome-wide knockout effort at the scale envisioned.

Who is eligible to apply?

Eligibility is limited to U.S.-based higher education institutions, including public/state-controlled and private institutions of higher education.

Are foreign (non-U.S.) institutions eligible to apply?

No. Foreign (non-U.S.) institutions are not eligible to apply.

Are non-domestic components of U.S. organizations eligible to apply?

No. Non-domestic components of U.S. organizations are not eligible to apply.

Are foreign components allowed in any form?

Yes. The FOA states that foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Which federal agency administers this funding opportunity?

The opportunity is administered by the National Institutes of Health (NIH) under the NIH Common Fund.

How is this opportunity categorized in terms of funding type?

It is categorized as discretionary funding.

What are the key dates provided for this opportunity?

The information provided includes a creation date of October 7, 2015, and an original closing date of December 9, 2015.

What CFDA numbers are associated with this program?

The program is associated with multiple CFDA numbers, including 93.113, 93.121, 93.172, and 93.173, among others, reflecting its cross-institute, cross-disease Common Fund scope.

What is the broader scientific value of the resource produced by this project?

By linking gene knockouts to standardized phenotypes, the resource is intended to accelerate functional genomics and improve interpretation of human genetic variation by providing experimentally grounded evidence about gene function.

What is emphasized to ensure the outputs are broadly usable?

The FOA emphasizes reproducibility, standard operating procedures, systematic data sharing, and standardized phenotyping so that results are comparable across time and usable by many research groups.

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