Opportunity Information: Apply for RFA HL 13 027

  • The National Institutes of Health in the health sector is offering a public funding opportunity titled "Functional Assays to Screen Genomic Hits (R21/R33)" and is now available to receive applicants.
  • Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.233 National Center on Sleep Disorders Research 93.837 Cardiovascular Diseases Research 93.838 Lung Diseases Research 93.839 Blood Diseases and Resources Research.
  • This funding opportunity was created on Oct 21, 2013 and posted on Oct 2, 2012.
  • Applicants must submit their applications by Nov 1, 2013. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
  • The funding agency has allocated a total of $2,500,000.00 to eligible and selected applicants.
  • Eligible applicants include: Private institutions of higher education City or township governments Others (see text field entitled Additional Information on Eligibility for clarification) For profit organizations other than small businesses Public and State controlled institutions of higher education County 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 Special district governments Independent school districts Native American tribal governments (Federally recognized) Public housing authorities/Indian housing authorities Small businesses Native American tribal organizations (other than Federally recognized tribal governments) State governments.
  • Other Eligible Applicants include the following Alaska Native and Native Hawaiian Serving Institutions Eligible Agencies of the Federal Government Faith based or Community based Organizations Hispanic serving Institutions Historically Black Colleges and Universities (HBCUs) Indian/Native American Tribal Governments (Other than Federally Recognized) Regional Organizations Tribally Controlled Colleges and Universities (TCCUs) U.S. Territory or Possession Non domestic (non U.S.) Entities (Foreign Institutions) are not eligible to apply. Non domestic (non U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
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Opportunity Summary:

The National Heart, Lung, and Blood Institute (NHLBI) released the funding opportunity announcement "Functional Assays to Screen Genomic Hits (R21/R33)" (Funding Opportunity Number RFA-HL-13-027) to support research that moves beyond identifying genetic associations and into testing what those genetic variants actually do. The central purpose is to fund functional analyses of specific genetic variations already implicated in heart, lung, blood, and sleep-related traits or diseases, using model systems that can realistically and convincingly measure biological impact. Projects are expected to start with clearly defined genomic "hits" and then apply appropriate experimental approaches, typically in vitro systems (such as relevant cell types, engineered cell lines, or organoid-like models) and/or animal models, to validate whether and how those variants influence measurable phenotypes.

The FOA is structured as an Exploratory/Developmental Phased Innovation award using the R21/R33 mechanism, which is meant to de-risk ambitious functional genomics work by separating early feasibility from later expansion. The first phase (R21) provides up to two years of support primarily for planning, assay development, preliminary functional testing, and feasibility studies that demonstrate the proposed strategy can work. If the R21 phase meets predefined goals, the project may transition to the second phase (R33), which can provide up to three additional years to scale up the research, deepen mechanistic studies, or broaden testing across additional variants, systems, or functional readouts. The total combined project period cannot exceed five years, and a key feature is that the R21 phase must include measurable milestones, meaning applicants need to spell out concrete, objective success criteria that can be evaluated to determine whether expansion into the R33 phase is justified.

Applications are expected to do more than list candidate variants. They should identify and justify which genetic variants will be tested, explain the evidence linking those variants to specific heart, lung, blood, or sleep phenotypes, and describe the functional measures that will be used to validate impact. In practical terms, that means applicants need to connect three elements in a coherent way: the variant(s) and why they are credible leads, the phenotype(s) being modeled or measured, and the experimental assays and endpoints that can plausibly show functional consequences. Because the emphasis is on "amenable" systems, the FOA implicitly favors strategies where the model and assay design are well matched to the biology of the trait and can produce interpretable results within the phased timeline.

In terms of administrative details, the opportunity is a discretionary NIH grant with an estimated total funding amount of about $2.5 million. It was posted October 2, 2012, with closing dates in late 2013 (original closing date October 23, 2013; current closing date listed as November 1, 2013), and an archive date of December 1, 2013. It is associated with multiple NIH/CFDA program areas relevant to NHLBI and sleep research, including 93.233 (National Center on Sleep Disorders Research) and the NHLBI research areas 93.837 (Cardiovascular), 93.838 (Lung), and 93.839 (Blood Diseases and Resources). Cost sharing or matching is not required.

Eligibility is broad across U.S.-based organizations, spanning public and private institutions of higher education, nonprofit organizations (including 501(c)(3) and non-501(c)(3)), for-profit organizations (other than small businesses as well as small businesses), and a wide range of government entities (state, county, city/township, special districts, independent school districts, and public housing authorities/Indian housing authorities). The FOA also lists many mission-focused and community-serving institution types as eligible, including HBCUs, Hispanic-serving institutions, tribally controlled colleges and universities, Alaska Native and Native Hawaiian Serving Institutions, and faith-based or community-based organizations, along with eligible federal agencies and U.S. territories or possessions. Foreign institutions and non-U.S. components of U.S. organizations are not eligible to apply, although foreign components as defined by NIH policy are allowed, which typically means limited collaboration elements may be permissible if they fit NIH rules.

Overall, this FOA is aimed at a specific bottleneck in modern genetics: large-scale association studies often produce lists of candidate loci, but turning those signals into biological understanding requires careful functional validation. NHLBI designed the R21/R33 structure to encourage applicants to propose practical, milestone-driven paths that start with feasibility and then, if successful, expand into a more comprehensive functional characterization of genetic variants tied to clinically and biologically important heart, lung, blood, and sleep outcomes.

Frequently Asked Questions (FAQs)

What is the goal of the "Functional Assays to Screen Genomic Hits (R21/R33)" funding opportunity?

The opportunity supports research that goes beyond finding genetic associations and focuses on testing what specific genetic variants actually do. The emphasis is on functional analyses of genomic "hits" already implicated in heart, lung, blood, and sleep-related traits or diseases, using model systems and assays that can convincingly measure biological impact.

Which NIH institute is sponsoring this opportunity?

The opportunity is released by the National Heart, Lung, and Blood Institute (NHLBI).

What is the Funding Opportunity Number (FOA number)?

The Funding Opportunity Number is RFA-HL-13-027.

What types of research projects does this FOA prioritize?

Projects are expected to begin with clearly defined genomic "hits" and then apply experimental approaches to validate whether and how those variants influence measurable phenotypes. The FOA favors strategies where the chosen model system and assay design are well matched to the biology of the trait and can produce interpretable results within the phased timeline.

Does the FOA focus on discovering new variants or testing known/implicated variants?

It focuses on testing specific genetic variations already implicated in relevant traits or diseases. Applications are expected to move past lists of candidates and into functional validation.

What disease or trait areas are included?

The FOA targets heart, lung, blood, and sleep-related traits or diseases, aligning with NHLBI mission areas and sleep research program areas.

What research approaches and model systems are encouraged?

The FOA anticipates functional testing in systems that can realistically measure biological impact, typically using in vitro systems (such as relevant cell types, engineered cell lines, or organoid-like models) and/or animal models.

What does "amenable" model systems mean in the context of this FOA?

It refers to model systems and assays that are well suited to the underlying biology of the trait and capable of producing clear, interpretable functional results within the R21/R33 phased time frame.

What is the R21/R33 mechanism and why is it used here?

This FOA uses an Exploratory/Developmental Phased Innovation award (R21/R33) to reduce risk for ambitious functional genomics projects by separating early feasibility work from later expansion. The R21 phase supports planning and feasibility, and successful projects may transition to the R33 phase for scaled-up and deeper studies.

How long is the R21 phase and what is it intended to support?

The R21 phase provides up to two years of support. It is primarily intended for planning, assay development, preliminary functional testing, and feasibility studies that show the proposed functional strategy can work.

How long is the R33 phase and what is it intended to support?

The R33 phase can provide up to three additional years. It is intended to scale up the research, deepen mechanistic studies, and/or broaden testing across additional variants, systems, or functional readouts.

What is the maximum total project period under this FOA?

The combined R21 and R33 project period cannot exceed five years.

Is transition from R21 to R33 automatic?

No. Transition to the R33 phase depends on whether the R21 phase meets predefined, measurable goals and milestones that justify expansion.

What are "milestones" and why are they important for this FOA?

Milestones are concrete, objective success criteria that can be evaluated to determine whether the project has demonstrated feasibility during the R21 phase. The FOA makes milestone-driven planning a key feature because it governs whether the project may move into the R33 expansion phase.

What should applicants include beyond naming candidate genetic variants?

Applications are expected to (1) identify and justify which variants will be tested, (2) explain the evidence linking those variants to specific heart, lung, blood, or sleep phenotypes, and (3) describe the functional measures, assays, and endpoints that will be used to validate impact.

How should an application connect variants, phenotypes, and assays?

The FOA expects a coherent link between the variant(s) (and why they are credible leads), the phenotype(s) being modeled or measured, and the experimental assays and endpoints that can plausibly show functional consequences.

What kind of outcomes or endpoints are expected?

The FOA emphasizes measurable phenotypes and functional readouts that can demonstrate whether and how the variants influence biology. The endpoints should be interpretable within the proposed model system(s) and the phased timeline.

What is the estimated total funding amount for this opportunity?

The estimated total funding amount is about $2.5 million.

Is this a discretionary grant program?

Yes. The FOA is described as a discretionary NIH grant opportunity.

When was the FOA posted and what are the key dates mentioned?

It was posted on October 2, 2012. The closing dates are listed in late 2013 (original closing date October 23, 2013; current closing date listed as November 1, 2013). The archive date is December 1, 2013.

Is cost sharing or matching required?

No. Cost sharing or matching is not required.

Which CFDA/program areas are associated with this FOA?

The FOA is associated with NIH/CFDA program areas including 93.233 (National Center on Sleep Disorders Research) and NHLBI research areas 93.837 (Cardiovascular), 93.838 (Lung), and 93.839 (Blood Diseases and Resources).

Who is eligible to apply?

Eligibility is broad across U.S.-based organizations, including public and private institutions of higher education; nonprofit organizations (both 501(c)(3) and non-501(c)(3)); for-profit organizations (including small businesses and other than small businesses); and many government entities such as state, county, city/township, special district, independent school district, and public housing authorities/Indian housing authorities.

Are mission-focused and community-serving institutions eligible?

Yes. The FOA lists many eligible institution types including HBCUs, Hispanic-serving institutions, tribally controlled colleges and universities, Alaska Native and Native Hawaiian Serving Institutions, and faith-based or community-based organizations.

Are U.S. territories or possessions eligible to apply?

Yes. The FOA includes eligible entities from U.S. territories or possessions.

Are federal agencies eligible applicants?

Yes. Eligible federal agencies are included among eligible applicant types.

Are foreign institutions eligible to apply?

No. Foreign institutions and non-U.S. components of U.S. organizations are not eligible to apply under this FOA.

Are foreign components allowed at all?

Yes. The FOA states that foreign components (as defined by NIH policy) are allowed, which typically means limited collaboration elements may be permissible if they fit NIH rules.

What is the main problem this FOA is trying to address?

It targets a common bottleneck in modern genetics: association studies can identify candidate loci, but converting those signals into biological understanding requires careful, well-designed functional validation. This FOA supports milestone-driven functional testing to bridge that gap.

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