Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Human Genome Research Institute (NHGRI)
National Cancer Institute (NCI)
National Eye Institute (NEI)
National Heart, Lung, and Blood Institute (NHLBI)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute on Drug Abuse (NIDA)
National Institute of Environmental Health Sciences (NIEHS)
National Institute of Mental Health (NIMH)
National Institute of Neurological Disorders and Stroke (NINDS)
National Center for Complementary and Integrative Health (NCCIH)

Division of Program Coordination, Planning and Strategic Initiatives, Office of Research Infrastructure Programs (ORIP)

Office of Research on Women’s Health (ORWH)

Funding Opportunity Title

Limited Competition: Knockout Mouse Production and Phenotyping Project (UM1) Clinical Trial Not Allowed

Activity Code

UM1 Research Project with Complex Structure Cooperative Agreement

Announcement Type

Reissue, RFA-RM-15-017

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-HG-21-036

Companion Funding Opportunity

RFA-HG-21-037 - Limited Competition: Knockout Mouse Phenotyping Project Data Coordination Center and Database (UM1 Clinical Trial Not Allowed)

Assistance Listing Number(s)

93.172; 93.213; 93.396; 93.867; 93.838; 93.837; 93.839; 93.840; 93.233; 93.866; 93.273; 93.855; 93.846; 93.865; 93.279; 93.173; 93.121; 93.847; 93.113; 93.853; 93.351; 93.313.

Funding Opportunity Purpose

 The purpose of the Knockout Mouse Phenotyping Project (KOMP2) is to produce a comprehensive resource of null-mutant mice, and associated phenotype data, for the purpose of elucidating functional information for each protein-coding gene in the mammalian genome. This Funding Opportunity Announcement (FOA) solicits applications for production and phenotyping centers that will make maximum progress toward completion of KOMP2 in a final five-year project period. The specific objectives are to generate approximately 1,200 mutant mouse lines using CRISPR/Cas9 technology, perform a series of phenotyping assays, cryopreserve germplasm, and make mice and data readily available to the research community.

This is a limited competition RFA. Only recipient organizations funded under (RFA-RM-15-017) are eligible to apply.

Key Dates
Posted Date

August 31, 2021

Open Date (Earliest Submission Date)

October 1, 2021

Letter of Intent Due Date(s)

Not Applicable

Application Due Date(s)

November 1, 2021

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s)

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

March 2022

Advisory Council Review

May 2022

Earliest Start Date

July 2022

Expiration Date

November 2, 2021

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

    Part 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. Funding Opportunity Description
    Section II. Award Information
    Section III. Eligibility Information
    Section IV. Application and Submission Information
    Section V. Application Review Information
    Section VI. Award Administration Information
    Section VII. Agency Contacts
    Section VIII. Other Information


    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description

    Background

    Defining the functional role of the complete set of protein-coding genes in the mammalian genome will have a transformative effect on biology and the understanding of human disease. The mouse has long been an important mammalian model system for the study of gene function in human health and disease, and the premiere embodiment of that is the ability to generate knockout (KO) mice. Mouse mutants with phenotypes mimicking human traits are critical research tools for understanding the genetics and physiological mechanisms underlying mammalian biology and disease.

    The original Knockout Mouse Program (KOMP) was launched in 2006 as a trans-NIH effort, stemming from discussions at a 2003 Cold Spring Harbor Laboratory Banbury Center meeting titled “Mouse Genome-wide Targeted Mutagenesis”. The KOMP project created 8,500 null alleles in embryonic stem cells derived from C57BL/6N. In 2011 the program was expanded as the Knockout Mouse Phenotyping Program (KOMP2), funded as a joint trans-NIH and Common Fund program, with the goal of generating and phenotyping mice strains. Since its launch, KOMP2 integrated operations with other members of the International Mouse Phenotyping Consortium (IMPC, http://www.mousephenotype.org/). IMPC scientists implemented uniform phenotyping protocols, data collection methods, and reporting standards, and made all data available via a data portal. Adoption of CRISPR technology in 2014 greatly increased the efficiency of this program. Presently, the KOMP2 research network has produced 5,500 strains and the IMPC has completed an additional 4,200 lines. To date, the KOMP Repository and Mutant Mouse Resource and Research Centers (MMRRC) have distributed over 39,000 products (vectors, Embryonic Stem (ES) cell lines, mice, and services) representing over 5,500 unique genes, which is a strong indication of the value and impact of the program. Importantly, these reagents have been used in 3,800 scientific publications by the research community (www.mousephenotype.org/data/publications).

    The current IMPC data release includes phenotype data for 7,590 genes, which are associated with 89,329 phenotype calls. There are now 599,052 images included (https://www.mousephenotype.org/news/data-release-14/). IMPC publications have described collections of genes with embryo lethal phenotypes, cardiovascular and metabolic phenotypes, deafness phenotypes, and ocular phenotypes (https://www.mousephenotype.org/understand/data-collections/). Statistical analysis has resulted in a plethora of novel gene-phenotype correlations in both well-studied and understudied genes. Because IMPC performs phenotype assays on male and female animals, the network has been able to describe wide-spread, significant effects of sex as a biological variable. Uptake of these data has been robust: web analytics indicate that between 2015 and 2020 about 100,000 unique users view nearly 1 million pages annually.

    Overall, this effort helps scientists explain the genetic basis of many different types of diseases in mice that also occur in humans, including rare diseases that have been under-studied as well as some common chronic diseases that affect much of the human population.

    Over the course of the program, the IMPC has increased its membership: the group currently comprises 22 centers across 6 continents. It is expected that the successful applicants to this FOA will coordinate with the other units of the KOMP2 research network and with the IMPC to identify knockout lines to be phenotyped, further harmonize phenotyping platforms, continue data integration and analysis, and make use of prior know-how and experience.

    Research Objective

    This FOA will support work to design and produce null-mutant mice and phenotype them. It is expected that centers will employ optimized CRISPR protocols for efficient production of null alleles in zygotes as part of a high-throughput pipeline. Targets will be selected from the remaining set of 1:1 human-mouse ortholog genes that do not have associated phenotype information. This FOA seeks to fund centers with a strong history in high-throughput knockout mouse production, a history of working in cooperative large-scale projects, an ability to be innovative and adaptive to new technologies, and the discipline to meet production standards and goals. The specific objectives of this FOA are for funded centers collectively to generate at least 300 mutant mouse lines each year during the first 4 years and deposit these strains at the MMRRC repositories. Furthermore, the funded centers will undertake broad-based phenotyping of mice at embryonic and juvenile ages. Specifically, for strains harboring mutations that cause embryonic lethality, mice will be examined using IMPC approved procedures (http://www.mousephenotype.org/impress). Examination of strains will follow IMPC approved procedures for phenotyping juvenile mice (up to 16 weeks of age). Data upload will follow standard IMPC procedures.

    See Section VIII. Other Information for award authorities and regulations.

    Section II. Award Information
    Funding Instrument

    Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

    Application Types Allowed

    Renewal

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

    Clinical Trial?

    Not Allowed: Only accepting applications that do not propose clinical trials

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    Issuing IC and partner components intend to commit an estimated total of ${37.5M total costs} to fund {3} awards.

    Award Budget

    Application budgets are not limited but need to reflect the actual needs of the proposed project.

    Award Project Period

    The maximum project period is 5 years.

    NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    Higher Education Institutions

    • Public/State Controlled Institutions of Higher Education
    • Private Institutions of Higher Education

    The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

      • Hispanic-serving Institutions
      • Historically Black Colleges and Universities (HBCUs)
      • Tribally Controlled Colleges and Universities (TCCUs)
      • Alaska Native and Native Hawaiian Serving Institutions
      • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

    Nonprofits Other Than Institutions of Higher Education

    • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
    • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

    For-Profit Organizations

    • Small Businesses
    • For-Profit Organizations (Other than Small Businesses)

    Governments

    • State Governments
    • County Governments
    • City or Township Governments
    • Special District Governments
    • Indian/Native American Tribal Governments (Federally Recognized)
    • Indian/Native American Tribal Governments (Other than Federally Recognized)
    • Eligible Agencies of the Federal Government
    • U.S. Territory or Possession

    Other

    • Independent School Districts
    • Public Housing Authorities/Indian Housing Authorities
    • Native American Tribal Organizations (other than Federally recognized tribal governments)
    • Faith-based or Community-based Organizations
    • Regional Organizations
    Foreign Institutions

    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.

    Required Registrations

    Applicant Organizations

    Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

    • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
    • System for Award Management (SAM)– Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.  Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
    • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

    Program Directors/Principal Investigators (PD(s)/PI(s))

    All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

    Eligible Individuals (Program Director/Principal Investigator)

    Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

    For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

    2. Cost Sharing

    This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

    3. Additional Information on Eligibility
    Number of Applications

    Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

    The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

    • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
    • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
    • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

     

    Section IV. Application and Submission Information
    1. Requesting an Application Package

    The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

    2. Content and Form of Application Submission

    It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

    Page Limitations

    All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

    For this specific FOA, the Research Strategy section is limited to 30 pages.

    Instructions for Application Submission

    The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

    SF424(R&R) Cover

    All instructions in the SF424 (R&R) Application Guide must be followed.  

    SF424(R&R) Project/Performance Site Locations

    All instructions in the SF424 (R&R) Application Guide must be followed.  

    SF424(R&R) Other Project Information

    All instructions in the SF424 (R&R) Application Guide must be followed.  

    SF424(R&R) Senior/Key Person Profile

    All instructions in the SF424 (R&R) Application Guide must be followed. 

    R&R or Modular Budget

    All instructions in the SF424 (R&R) Application Guide must be followed.

    R&R Subaward Budget

    All instructions in the SF424 (R&R) Application Guide must be followed.

    PHS 398 Cover Page Supplement

    All instructions in the SF424 (R&R) Application Guide must be followed.  

    PHS 398 Research Plan

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: 

    Research Strategy: The Research Strategy should consist of the following subsections, uploaded as a single pdf attachment.

    A) Overall Goals

    B) Animal Production and Cryopreservation Section

    C) Phenotyping Section

    D) Research Management Plan

    A) Overall Goals

    Plans for the Continued Production and Phenotyping of KO Mice: State concisely the goals of the proposed project and summarize the expected outcomes, including the contributions that the Production and Phenotyping center will make to the IMPC and the impact it will have on the research fields that it encompasses.

    Describe briefly the applicant’s prior experience with mouse production and phenotyping contributions to the KOMP2 research network. Describe the overall design, development, and advancement of the production and phenotyping, and then provide a general overview of how the resources generated by the project have been made available rapidly and efficiently to the biomedical community.

    Describe the organization of the proposed center and its management structure, including integration of the components to maintain efficient operation; key personnel; and reporting relationships. Furthermore, the application should describe how the center would be integrated into the KOMP2 research network, including how they will coordinate their efforts with the other units of the KOMP2 research network and with the IMPC.

    B) Animal Production and Cryopreservation Section

    State concisely the goals of the proposed Animal Production and Cryopreservation Section and summarize the expected outcomes.

    Progress Report: The applicant should include a detailed report describing activities related to high throughput production of knockout strains, and their cryopreservation, during the last 5 years. The applicant should describe experience with adapting CRISPR/Cas9 technology to generate knockout strains in a high-throughput environment.  

    Gene Selection: It is expected that each center will generate at least 100 germline-confirmed knockout mouse lines per year (for a minimum of 400 lines over the first 4 years), with a preference for genes that are 1:1 human: mouse orthologs and have little or no experimentally derived functional annotation. Applicants should describe and justify their process for gene selection.

    Knockout Animal Production and Breeding Cohorts for a Phenotyping Pipeline: The proposed plan should describe the design and development of the CRISPR-based production pipeline, its capacity, and the presence of required expertise. The plan should describe procedures for efficient generation of defined deletions in mice, genetic screening methods, animal breeding schemes, and workflows for scaled mouse production. The plan should include assessment of embryonic lethality, fertility, and fecundity of homozygous mice. Centers should establish and expand breeding colonies to produce homozygous or (for lethal or subviable lines) heterozygous mice and provide them as cohorts to the phenotyping pipelines. Applicants should describe the available space that will be utilized for the breeding of the mice.

    Cryopreservation and Submission to Repositories: The applicant should describe methods for cryopreservation of germplasm and the timeline for submission to the MMRC. The applicant should allocate budget for shipment of the biomaterials, if they are not co-located with a designated MMRRC.

    Finally, applicants should present:

    • the overall projected throughput of the proposed center and how it will be attained;
    • proposed methods to utilize innovative technologies and improve the efficiency of generating knockout mice and quality of the cryopreserved germ cells.
    • potential bottlenecks or other problems that can be anticipated as well as proposed solutions or alternatives;
    • timelines and quantitative milestones, where appropriate.

    Quality Control: The applicant should discuss any steps that will be taken to determine and ensure the quality of the resources that will be generated. Examples of appropriate quality control procedures include those for a) characterization of the targeted allele; b) testing for off-target activity; c) detection and elimination of off-target events; d) definition of genetic screening procedures; e) defining efficiency of embryo or sperm cryopreservation and cryo-recovery; and f) testing the pathogen status of biological reagents. The applicant should discuss briefly their proposed animal husbandry conditions and their approaches to monitoring animal health. Evidence of the effectiveness of the proposed quality control programs should be included.

    Information Technology: The applicant should discuss all pertinent informatics issues. These include, but are not limited to, the informatics infrastructure of the production system, such as the basic IT infrastructure/system administration; the laboratory information management system; and the system for data handling and deposition. The application should describe how data submission procedures would accommodate the IMPC required data format and submission at determined frequencies.

    Technology Development: Provide documentation of experience in developing and applying new and improving extant technologies for mouse production, distribution, and cryopreservation. Describe how a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, or instrumentation will be achieved and integrated into the production efforts. Describe how technology improvements will increase the efficiency and decrease the cost of high-throughput production processes. For example, continued optimization of CRISPR/Cas9 technology is particularly relevant. This could include improving efficiency of the procedures such as prediction and testing of the off-targets effects, decreasing mosaicism, simultaneous injection of guides for multiple target gene modifications, and further improvement of the screening tools. For example, effective implementation of machine-readable tags for individual mouse tracking and monitoring and further development of cryopreservation technologies and increasing efficiency of cryo-recovery are particularly relevant.

    C) Phenotyping Section

    State concisely the goals of the proposed Phenotyping Section and summarize the expected outcomes.

    Progress Report: A detailed progress report describing activities related to high-throughput phenotyping of knockout strains for the last 5 years should be included. The applicant should describe the average number of phenotype assays performed per month during this time period, design of the pipeline, rationale for the cohort size of mutants and controls, and any other internal metrics that the applicant has found to be useful in evaluating and managing the phenotyping of mice. Include a description of the expertise and training for staff to perform phenotyping assays.

    Embryo Phenotyping: The applicant should describe in detail the phenotyping assays to be employed. The current approved IMPC pipeline (http://www.mousephenotype.org/impress) should be used as a template for the phenotyping pipeline. The applicant should address the process and ability to perform standard IMPC phenotyping assays, including the size of cohorts needed for each assay; the timing of the tests; and the source and numbers of wild type mice needed for controls in the phenotyping assays. In addition, the applicant can propose novel methods to identify essential genes by in vitro methods and justify these approaches.

    The ability to harmonize phenotyping platforms and cooperate with the international efforts is an important criterion for evaluation of the applications. Included in this is the flexibility to add, modify or drop tests as the project progresses. Applicants should address their ability to adopt new procedures. Additionally, the applicant can propose, with adequate scientific justification, modifications to the standard pipeline.

    All phases of the embryo phenotyping process must be addressed as well as:

    • the overall projected throughput of the proposed center and how it will be attained;
    • potential bottlenecks or other problems that can be anticipated as well as proposed solutions;
    • stages of embryo analysis and any triage decision methodologies;
    • imaging modalities utilized at each stage (e.g., microCT);
    • data capture, image analysis, and data storage systems and methods;
    • timelines and quantitative milestones, where appropriate.

    Juvenile Phenotyping: The applicant should describe in detail the phenotyping assays to be employed. The current approved IMPC pipeline (http://www.mousephenotype.org/impress) should be used as a template for the phenotyping pipeline. The applicant should address the process and/or ability to perform standard IMPC phenotyping assays, including the size of cohorts needed for each assay, the timing of the tests, and the source and numbers of wildtype mice needed for controls in the phenotyping assays.

    The ability to harmonize phenotyping platforms and cooperate with the international efforts is an important criterion for evaluation of the applications. Included in this is the flexibility to add, modify or drop tests as the project progresses. The applicants should address their ability to adopt new procedures. The applicant can propose, with adequate scientific justification, modifications to the standard pipeline. A cost benefit analysis of phenotyping assays, including hit rates and clinical relevance, is encouraged to justify inclusion or dropping assays from the current and proposed pipelines.

    All phases of the phenotyping process must be addressed as well as:

    • the overall projected throughput of the proposed center and how it will be attained;
    • potential bottlenecks or other problems that can be anticipated as well as proposed solutions;
    • cost breakdowns of assays or groups of assays by lines analyzed;
    • timelines and quantitative milestones where appropriate.

    Quality Control (QC): The applicant should discuss any additional means that will be taken to determine and ensure the quality of, or otherwise validate, the resources that will be generated, beyond those mentioned above. Examples of appropriate QC procedures include those for validation of phenotyping procedures and data, such as QC of assays and data collection. The application should include QC procedures for each assay employed in the phenotyping platforms and the frequency of the QC. Examples of appropriate QC procedures include those for confirmation of the targeted allele, periodic validation of equipment and assays, data integrity, data validity, and testing the pathogen status of all biological reagents. Evidence of and experience in the effectiveness of the proposed QC programs should be included.

    IT Requirements: The applicant should discuss all pertinent informatics issues. These include, but are not limited to, the informatics infrastructure of the phenotyping systems, such as the basic IT infrastructure/system administration, the laboratory information management system, and the system for data handling and deposition. It is vital that the phenotyping data be provided in a format that can be easily uploaded to the IMPC database. The application should describe activities related to the timely uploads of the data in a standardized format, subsequent coordination/communication with data wranglers and with the statistics working group. The applicant should describe a process to resolve issues, with the goal of improving data throughput.

    Technology Development: Incremental technology improvements will play an important role in increasing the efficiency and decreasing the cost of high-throughput phenotyping of mouse knockouts. Providing phenotypic information that is accurate, sensitive, reliable and reproducible is critical to gain a better understanding of the relationship between genes and phenotypes. The application should describe the applicant’s efforts to use modern automated technologies and methodologies for phenotypic assays with a goal to generate a large number of measurements using a limited number of animals. The applicant should explore the full potential of laboratory techniques that can be adaptable to high-throughput procedures.

    D) Research Management Plan

    The application should describe a management plan commensurate with the complexity of this effort, including integration of the separate components to maintain an efficient operation. This includes a description of key personnel, section leaders and internal reporting relationships and mechanisms for reporting progress to NHGRI and ORIP/DPCPSI (see Terms and Conditions, below) as well as the decision-making process. Include how this management plan will support the achievement of the proposed goals and milestones of the project and should involve regular evaluation of production and phenotyping and scientific progress. The proposed management plan should ensure appropriate prioritization of activities, including a process to reallocate resources as needed, and should describe how problems will be identified and resolved. The plan should also encourage and provide training for personnel, and enhance the visibility and effectiveness of the efforts. This section should also describe in detail the progress tracking of the production and phenotyping pipelines

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

    All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Awardees are expected to comply with the NIH Genomic Data Sharing (GDS) Policy. NHGRI supports the broadest appropriate genomic, phenotypic, and metadata data sharing with timely data release through widely accessible data repositories. Per NOT-HG-21-022, NHGRI expects applications awarded under this FOA to share comprehensive metadata and phenotypic data associated with the study, use standardized data collection protocols and survey instruments for capturing data, as appropriate, and use standardized notation for metadata (e.g., controlled vocabularies or ontologies) to enable the harmonization of datasets for secondary research analyses. For more information on NHGRI’s genomic data sharing expectations, see the NHGRI’s Genomic Data Sharing Policy FAQs webpage. Therefore, responses to this FOA should propose a specific and comprehensive plan for the rapid release of data resulting from the knockout mouse production and phenotyping effort to the appropriate databases. Rapid release of the data to the scientific user community is a key component of the KOMP2 project because of the scope of this community resource project as described in this FOA and because of the national and scientific investment that the NIH will make in KOMP2. Accordingly, applicants should promote innovative methods for achieving the maximum use of the KOMP2 resource.

    Applicants should propose a data sharing plan consistent with this goal that addresses rapid data sharing with the community and describes plans to adhere to the FAIR Guiding principles (Findable, Accessible, Interoperable, Reusable), including:

    • Data and metadata assigned unique and persistent identifiers.
    • Data and metadata retrievable using standardized protocols/Application Programming Interfaces (API).
    • Data pass strict quality metrics.
    • Data have clear provenance.
    • Rich metadata are collected with all data.
    • Wherever possible, community-standard formats, vocabularies, ontologies, quality metrics are used.
    • Plans for sharing protocols and methodologies should be included.

    Investigators responding to this funding opportunity should include a Plan for Sharing Research Resources addressing how unique research resources will be shared or explain why sharing is not possible. NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value and further the advancement of the research. Therefore, the applicant's data release plan should address how software or other resources developed under this funding will be publicly released. Applicants should not feel constrained to propose a standard plan for sharing materials, given the scope of KOMP2 as defined by the FOA and the NIH's investment in this project. Widespread dissemination and access to the materials generated through this program to the public and private research sectors are an aim of this FOA and will require innovative methods for achieving the maximum use of the resource to be produced under this project.

    Sharing Model Organisms Plan. As the production of gene knockout mice, frozen sperm and embryos are an integral part of the KOMP2 project, all applicants are expected to include a description of a specific plan for sharing and distributing unique model organisms or state why such sharing is restricted or not possible. To enable ready access to these materials, a uniform MTA such as the Simple Letter Agreement (SLA) or Condition of Use statement is preferred for all recipients who receive resources made by this effort to ensure that the resources made by this initiative are available in a manner consistent with the goals of this FOA and with no additional reach-through rights to inventions/discoveries made by the end users. Although NIH Policy strongly discourages the patenting of research resources, applicants are free to patent their discoveries so long as the embryos, mice, and data are made available for research purposes in a manner consistent with the NIH Data Sharing Policy, other NIH sharing policies (http://grants.nih.gov/grants/sharing.htm), and achieving the goals of this FOA.

    Authorization and Consent

    (a) The Government authorizes and consents to all use and manufacture of any invention described in and covered by a United States patent in the performance of this Cooperative Agreement at all tiers.

    Notice and Assistance Regarding Patent and Copyright Infringement.

    (b) The Recipient organization shall report to the Program Director, promptly and in reasonable written detail, each notice or claim of patent or copyright infringement based on the performance of this Cooperative Agreement of which the Recipient organization has knowledge.

    (c) In the event of any claim, suit, threat of a claim or suit, or in the event that a patent-owner alleges the relevance of a patent and the Government agrees to enter into discussions related thereto, on account of any alleged patent or copyright infringement arising out of the performance of this Cooperative Agreement against the Government or out of the use of any supplies furnished or work or services performed under this Cooperative Agreement, the Recipient organization shall furnish to the Government, when requested by the Program Director, all evidence and information in possession of the Recipient organization pertaining to such suit or claim. Such evidence and information shall be furnished at the expense of the Government except where the Recipient organization has agreed to indemnify the Government.

    (d) The Recipient organization agrees to include, and require inclusion of, this clause in all sub-awards and subcontracts at any tier for supplies or services (including construction and architect-engineer sub-awards and subcontracts and those for material, supplies, models, samples, or design or testing services).

    Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award".

    Appendix:

    Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

    PHS Human Subjects and Clinical Trials Information

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

    All instructions in the SF424 (R&R) Application Guide must be followed.

    Delayed Onset Study

    Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

    All instructions in the SF424 (R&R) Application Guide must be followed.

    PHS Assignment Request Form

    All instructions in the SF424 (R&R) Application Guide must be followed. 

    3. Unique Entity Identifier and System for Award Management (SAM)

    See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

    4. Submission Dates and Times

    Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

    Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

    Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

    Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

    All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

    Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

    7. Other Submission Requirements and Information

    Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

    Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

    For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

    Important reminders:

    All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

    The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

    See more tips for avoiding common errors.

    Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

    In order to expedite review, applicants are requested to notify the National Human Genome Research Institute Referral Office by email at grahambj@exchange.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

     

    Post Submission Materials

    Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

    Section V. Application Review Information
    1. Criteria

    Only the review criteria described below will be considered in the review process.

    Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

    Overall Impact

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

    Scored Review Criteria

    Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

    Significance

    Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  Does the center serve the needs of investigators in a variety of research areas rather than in a single or few areas? Will the project resources be available to investigators on a local, regional, and national basis?

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?  Are the PD(s)/PI(s) appropriately trained and well suited to manage such a large and complex project?

    Innovation

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Are the overall design of the center, mouse production and cryopreservation as well as phenotyping pipeline innovative? Does the application utilize innovative approaches to rapidly provide the project data and resources to the biomedical community?  Is the technology development aspect of the application innovative?

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

    Are the organization, management structure, integration of the components, key personnel and reporting relationships well described and appropriate? Is the project well integrated with the broad-based phenotyping activity of the KOMP2 research network? Are adequate approaches proposed for enhancement of the capacity to utilize innovative technologies and improve the efficiency of generating phenotyping data?

    If the project involves human subjects and/or NIH-defined clinical research, are the plans to address

    1) the protection of human subjects from research risks, and

    2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?  

    Environment

    Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? 

    Additional Review Criteria

    As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

    Review Criteria for Animal Production and Cryopreservation

    The Animal Production and Cryopreservation Section will receive a merit descriptor (outstanding, acceptable, unacceptable) based on consideration of the following questions:

    • Does the PD/PI provide evidence of team experience in reliable, high-throughput production of high-quality knockout strains and their cryopreservation?
    • Are strategies for the Cas9-based production pipeline described in detail and will the approach support generation of the required number of knockout mouse lines per year?
    • Are the procedures for efficient generation of defined deletions in mice, genetic screening methods, animal breeding schemes, and workflows for scaled mouse production sufficiently robust to support this project?
    • Is the plan for assessment of embryonic lethality, fertility and fecundity of homozygous mice included and adequate to support the goals of the project?
    • Are the plans and procedures for establishing breeding colonies and providing cohorts to the phenotyping pipeline well described and adequate?
    • Are the production timelines and milestones sufficiently detailed?
    • How well are pertinent informatics issues presented, including the informatics infrastructure of the production system such as the basic IT infrastructure/system administration, the laboratory information management system, and the system for data handling and deposition?
    • Are the plans to ensure that the production data can be easily uploaded to the DCC and that production data will include sufficient tracking information well described and adequate?
    • Are the QC tests for embryo or sperm cryopreservation and cryo-recovery well described and will they ensure the required preservation of the generated resources?
    • Is it likely that technology improvements described in this section will increase the efficiency and decrease the cost of high-throughput production processes? 

    Review Criteria for Phenotyping

    The Phenotyping Section will receive a merit descriptor (outstanding, acceptable, unacceptable) based on consideration of the following questions:

    • Do the PDs/PIs have sufficient experience in high-throughput phenotyping of knockout strains?
    • Is expertise or training of staff, relevant to performing phenotyping assays, adequate for such a complex project?
    • Is evidence provided that the phenotyping tests are harmonized with international efforts and do the centers appear to have flexibility to add, modify or drop tests as the project progresses?
    • Are cost benefit analyses reasonable and is the rationale for inclusion or exclusion of assays from the current pipeline well justified?
    • Are quality control procedures, such as those for validation of phenotyping results and data integrity, validation of equipment, and testing the pathogen status of mice, well described and adequate?
    • Is the informatics infrastructure for colony management and tracking, the laboratory information management system, and the system for data handling and deposition to the Data Coordination Center sufficiently robust to support the project?
    • Is it likely that technology development approaches will increase the efficiency and decrease the cost of the high-throughput phenotyping of mouse knockouts?

    Review Criteria for Management Plan

    The Research Management Plan Section will receive a merit descriptor (outstanding, acceptable, unacceptable) that reflects the following:

    • Is the proposed management plan commensurate with the complexity of the effort, including integration of the separate components to maintain efficient operation, key personnel, section leaders, internal reporting relationships and mechanisms for reporting progress to NHGRI and ORIP/DPCPSI (see Cooperative Agreement Terms and Conditions, below)?
    • Is the internal evaluation of production and phenotyping sufficient?
    • Is the decision-making process clear and rational?
    • Is the management plan thorough and comprehensive?
    • Is the plan to coordinate with the IMPC well described and adequate?
    • Does the plan adequately address evaluation activities, including progress reports, site visits, and additional communication and materials to the NIH as needed? 
    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

    For research that involves human subjects and meets the criteria for one or more of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

    Inclusion of Women, Minorities, and Individuals Across the Lifespan 

    When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

    Vertebrate Animals

    The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

    Biohazards

    Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

    Resubmissions

    Not Applicable

    Renewals

    For Renewals, the committee will consider the progress made in the last funding period.

    Revisions

    Not Applicable.

    Additional Review Considerations

    As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

    Applications from Foreign Organizations

    Not Applicable

    Select Agent Research

    Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

    Resource Sharing Plans

    Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

    Authentication of Key Biological and/or Chemical Resources:

    For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

    Budget and Period of Support

    Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by{ the National Human Genome Research Institute }, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

    As part of the scientific peer review, all applications will receive a written critique.

    Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

    Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the NHGRI National Advisory Council. The following will be considered in making funding decisions:

    • Scientific and technical merit of the proposed project as determined by scientific peer review.
    • Availability of funds.
    • Relevance of the proposed project to program priorities.
    3. Anticipated Announcement and Award Dates

    After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

    Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

    Section VI. Award Administration Information
    1. Award Notices

    If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

    A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient’s business official.

    Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

    Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

    Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

    2. Administrative and National Policy Requirements

    All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

    Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex.  This includes ensuring programs are accessible to persons with limited English proficiency.  The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS.  Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

    HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.  For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

    Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.    

    In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

    Cooperative Agreement Terms and Conditions of Award

    The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 2 CFR Part 200, 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

    The administrative and funding instrument used for this award will be managed as a cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with recipient. Specific tasks and activities may be shared within the consortium and with the NHGRI staff as defined below.

    The PD(s)/PI(s) will have the primary responsibility for:

    • Determining research approaches, designing protocols, setting project milestones and timelines, and conducting research.
    • Ensuring that the data, software, resources, materials, etc. produced as part of this project are released appropriately according to the Resource Sharing Plan.
    • Preparing abstracts, presentations, and publications in a timely manner.
    • Adhering to policies regarding sharing of genomic and other types of data, data access, and standardized formats; timely publication; and intellectual property established by the NIH, NHGRI, ORIP, and the Steering Committee (SC).
    • Not disclosing confidential information.
    • Interacting with other relevant NHGRI, ORIP, and NIH activities, as needed, to promote synergy and consistency among similar or related projects.
    • Collaborating with the Data Coordination Center and Database (DCCDB) and other members of the consortium. Recipient organizations that are part of a consortium will work collaboratively with a DCCDB that is tasked with a variety of roles, such as: ensuring that the products are the highest quality, developing standards; disseminating information; providing logistics, outreach and training, etc.
    • In order for the collaboration to be effective, PDs/PIs are responsible for:
    • Ensuring that the recipient organization receives the appropriate approvals for sharing data between the DCCDB and selected data repositories such as, MGD, DBGaP, and ClinGen and other appropriate public databases.
    • Transferring, in a timely manner, detailed (sequence, variant, phenotypic, etc.) and related data and metadata, as appropriate, to the DCCDB, using agreed-upon formats and processes, to facilitate dissemination of data more broadly through databases such as MGD, DBGaP, and ClinGen and other appropriate databases.
    • Collaborating with the DCCDB to establish data formats and standards, to track and document collaborations and incoming samples, report findings, etc.
    • Submitting periodic progress reports in a standard format, including metrics of the use and impact on the community, agreed on with the NHGRI Project Scientist/Scientific Officer (PS/SO) or the SC.
    • Providing reports, summary statistics, and data, as appropriate, in a timely fashion as agreed upon by the SC.
    • Sharing research resources, tools, and data of interest with members of the consortium consistent with achieving the goals of the project.
    • Assessing and disseminating data, protocols, consent materials, and methods developed for or derived from the DCCDB within and outside the Consortium.
    • Abiding by common definitions, protocols, and procedures.
    • Attending and participating in SC and other working group meetings and accepting and implementing decisions made by the SC

    Consistent with 45 C.F.R. 75.322, the recipient will own the data and software developed under this award and be able to continue to use these data and software upon expiration or termination of the award. NIH will have unrestricted access to and use of the data and software, including the right to transfer them to other resource projects for their use, distribution, and integration with other data. NIH expects that the recipient will grant other resources the ability to use and redistribute the data, including integrating the data with other datasets, without restriction, unless otherwise limited by consent requirements.

    NHGRI and ORIP staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

    The Project Scientist/Scientific Officer (PS/SO) at NHGRI or ORIP is a dual role held by a Program Director. In the Project Scientist role, the Program Director will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. In the Scientific Officer role, the Program Director will be responsible for the normal scientific and programmatic stewardship of the award and manages concerns about bias as it affects the project. The role of PS/SO will be to facilitate and not to direct the activities. The PS/SO will be named in the Notice of Award.

    The PS/SO will have the following substantial involvement:

    • Serving as a liaison, helping to coordinate activities among and for the awardees, including acting as a liaison to the NIH and as an information resource for the awardees about genome research activities. The PS/SO will also coordinate the efforts of the recipient organization(s) with other groups conducting similar studies.
    • Reporting periodically on the progress of the recipient organizations to IC Directors.
    • Assisting recipient(s) in the development, if needed, of policies for dealing with situations that require coordinated action, including coordination with other NIH, national or international efforts.
    • Providing advice on the management and technical performance of the award.
    • Assisting in promoting the availability of the data and related resources developed in the course of the award to the scientific community.
    • Being responsible for the normal scientific and programmatic stewardship of the award, including assessments of how well the recipient has met any milestones required for each year of funding.  
    • Curtailing, withholding or reducing support for any recipient that fails to make satisfactory progress toward the approved work scope, has ethical or conflict of interest issues, or fails to comply with the Terms and Conditions of Award.
    • Involving NIH staff who may assist the recipient(s) as designated by the PS/SO.
    • Where warranted and consistent with authorship and conflict of interest requirements of journals in which the Consortium/Network decides to publish, co-authoring manuscripts through their role in scientific program management.

    External Scientific Panel (ESP): The NHGRI PS/SO may engage external scientists with relevant scientific and consortium experience, who are not funded as part of the project and who agree to a confidentiality policy, to provide input and advice to the NHGRI PS/SO about the project. The PS/SO will appoint 4-6 scientists to the ESP and will determine the durations of service. Activities of the ESP could include:

    • Participating, as appropriate, in consortium meetings, Steering Committees calls, and the annual recipient organizations’ meetings; a subset of ESP members may also meet remotely at other times during the project period, as needed.
    • Reviewing and evaluating the progress of recipient organizations (individually or as a group) in achieving the goals of the project.
    • Recommending changes in priorities based on scientific advances within and outside the consortium;
    • Providing individual recommendations regarding any changes in the project or grant(s) as necessary. The PS/SO will use these recommendations to make project changes, as appropriate.

    Areas of Joint Responsibility:

    Close interaction between the participating recipient organization(s) and the PS/SO will be required, to manage, assess, and implement the goals of the consortium. This is accomplished by:

    • Establishing a Steering Committee (SC): The SC will be the main governing body of the Consortium. The purpose of the SC will be to recommend directions for a consortium consistent with achieving the project goals, develop consortium policies to build synergy and improve communication and collaboration between the projects, and to provide a forum for discussing progress, challenges and opportunities for the consortium.
    • The SC will be composed of one representative from each of the grants awarded in consortium. Each PD/PI will decide who will be its representative. Multi-PI grants will have one representative. Each representative will have one vote; The PS/SO will be a voting member.

    Responsibilities of the SC will include:

    • Meeting monthly to share information on data resources, methodologies, analytical tools, data analyses, preliminary results, etc.
    • Establishing best practices for data integration and collaborative analyses as appropriate.
    • Setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted.
    • Generating responses to ESP recommendations by deadlines agreed upon by the SC and ESP members.
    • The SC may establish working groups to oversee the development and implementation of consortium policies and procedures. Working groups may be either permanent or time limited, may include additional experts, depending on the needs of the research.
    • The PD(s)/PI(s) will be expected to play an active role in these working groups, as appropriate.
    • It is expected that most of the decisions on the activities of the SC will be reached by consensus. If a vote is needed, at least 60% of the voting members most vote in favor of the proposal.
    • NIH staff will review and approve policies developed by the SC.
    • Awardees will be required to accept and implement policies approved by the SC.
    • The PS/SO will assist and facilitate the group process and not direct it.

    Dispute Resolution:

    Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NHGRI or ORIP may be addressed by convening a Dispute Resolution Panel.  It will be composed of three members: a designee of the SC chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of disagreement for one award, the first member may be chosen by that recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

    3. Reporting

    When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

    A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

    The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

    In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

    Section VII. Agency Contacts

    We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

    Application Submission Contacts

    eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

    Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
    Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

    General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
    Email: GrantsInfo@nih.gov (preferred method of contact)
    Telephone: 301-945-7573

    Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
    Contact Center Telephone: 800-518-4726
    Email: support@grants.gov

    Scientific/Research Contact(s)

    Colin Fletcher
    National Human Genome Research Institute (NHGRI)
    Telephone: 301-496-7531
    Email: fletcherc2@mail.nih.gov

    Oleg Mirochnitchenko
    Office of the Director, National Institutes of Health (NIH)
    Telephone: 301-435-0748
    Email: oleg.mirochnitchenko@nih.gov

    Peer Review Contact(s)

    Rudy Pozzatti, Ph.D.
    National Human Genome Research Institute (NHGRI)
    Telephone: 301-402-8739
    Email: mailto:pozzattr@exchange.nih.gov

    Financial/Grants Management Contact(s)

    Donna Morris
    National Human Genome Research Institute (NHGRI)
    Telephone: 301-827-2745
    Email: donna.morris@mail.nih.gov

    Section VIII. Other Information

    Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

    Authority and Regulations

    Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52, 45 CFR Part 75, and 2 CFR Part 200.

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