Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute on Aging (NIA)
Funding Opportunity Title	Collaborative Research Infrastructure to Develop Research Strategies to Identify Potential Therapeutic Targets Based on Genetic Factors Influencing Human Life Span and Health Span (U24)
Activity Code	U24 Resource-Related Research Projects Cooperative Agreements
Announcement Type	New
Related Notices	July 10, 2014 - Notice of Intent to Publish a Funding Opportunity Announcement for "Research Planning Infrastructure to Develop Therapeutic Target-ID Strategies Based on Favorable Genetic Variants of Human Longevity or Health Span (U24)". See Notice NOT-AG-14-020. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.
Funding Opportunity Announcement (FOA) Number	RFA-AG-14-003
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.866
Funding Opportunity Purpose	This FOA solicits applications for a U24 Cooperative Agreement project to support a collaborative research infrastructure that includes a team of multidisciplinary scientists to plan translational research strategies to identify potential therapeutic targets based on findings of genetic factors influencing human lifespan and health span. In the context of this FOA, the term "target identification strategy" refers to a concerted set of applied research approaches to address a key step in the development of new therapeutic or preventive interventions, or repurposing existing interventions to delay onset of age-related conditions, including identification of molecules or pathways by which activities could be favorably modified. Crucial types of expertise for the multidisciplinary team should include genetics, epidemiology, physiology, gerontology, cell biology, biotechnology, statistics, and bioinformatics. Activities supported through this award may include information exchange, database and informatics development, pilot studies, and analyses of existing data sets. Implementation of studies beyond pilot studies or exploratory data analysis is outside the scope of this FOA. Support for such studies could be requested in the future through other funding mechanisms. New population or family studies on genetic factors influencing longevity are also outside the scope of this FOA.

Posted Date	July 18, 2013
Open Date (Earliest Submission Date)	October 4, 2013
Letter of Intent Due Date(s)	October 4, 2013
Application Due Date(s)	November 4, 2013, by 5:00 PM local time of applicant organization. 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	February/March 2014
Advisory Council Review	May 2014
Earliest Start Date	July 2014
Expiration Date	November 5, 2013
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the 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.

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

Human genetic variants that favorably influence both longevity and risk of age-related diseases have been identified, as have variants associated with protection against age-related chronic diseases. The number of such variants identified is likely to increase in the relatively near future. Ongoing additional analyses in a variety of population based cohort studies and/or the use of new genomic platforms are likely to clarify the presence or absence of significant relationships between other variants and longevity. In addition, genomic findings related to life or health span in animal models or comparisons between humans and other species of varying life spans are likely to suggest potential therapeutic targets for interventions that could favorably influence human life or health span.

Evidence indicating that there are good prospects for therapeutic target identification based on such findings comes from development of therapeutics in other fields. An example is provided by the follow-up of the finding of the loss-of-function PCSK9 variants which are associated with diminished LDL cholesterol and cardiovascular disease risk by clinical testing of the effects of anti-PCSK9 antibodies on LDL cholesterol. Similarly, novel potential therapeutic targets could be identified based on knowledge of functional pathways of gene variants associated with longevity. Because longevity is associated with diminished risk for a variety of conditions, targets identified through such strategies may be particularly valuable for protection against multiple age-related conditions rather than just a single disorder.

An increasing variety of techniques to apply in target identification strategies based on genetic variation are being developed in both academia, industry and within NIH. The recent advent of novel high-throughput genomic tools and technologies, such as microarrays and next generation sequencing, has resulted in accumulation of genetic, genomic and epigenetic information from population-based studies spanning a wide range of ages. Using this genetic and phenotypic information would be fruitful in evaluating relationships of specific life span and health span related variants to a variety of other phenotypes in order to identify pathways that may be associated with the variant. In addition, new biotechnology approaches such as gene editing and use of iPS cell lines allow more rigorous and focused functional studies to aid in target identification.

Effective concerted use of these approaches in target identification based on genetic findings related to human longevity requires collaboration among several diverse research fields that have rarely interacted in aging research. It requires a multidisciplinary team capable of integrating relevant information from genetics, epidemiology, physiology, gerontology, cell biology, biotechnology, statistics and bioinformatics in order to select and design the most promising target-identification strategies. Expertise in strategies for applied research, such as those used by industry in drug development, is also likely to be crucial.

To date, no such team exists to conduct target identification strategies based on human longevity-related genomic findings. The present FOA requests applications for a team that will conduct the preliminary activities (described in the following section) that are needed for the development of target identification strategies in the future.

The proposed project should establish a collaborative research infrastructure with sufficient breadth of scientific expertise, staff time commitment, organizational structure, and operational procedures for information sharing and decision-making to complete planning and evaluation of a number of potential target identification strategies within the five-year award period. The collaborative research infrastructure should consist of a multidisciplinary team with representatives from the fields of genetics, epidemiology, physiology, gerontology, cell biology, biotechnology, statistics, and bioinformatics and, where appropriate, industry or other private sector liaisons. The infrastructure should also develop working relationships with staff of key information sources to facilitate data access and exchange, and identify and utilize resources and additional expertise available at the institutions of team members as needed for the project.

The research infrastructure should conduct the following activities. Relative degree of emphasis placed on specific aspects of these activities will depend on the variants selected and the amount of existing relevant information regarding them.

1. Create a central resource of relevant data and computational tools

Survey potential sources of existing data from genomic databases (including comparisons of humans with other species), informatics resources, computational tools, and analytic techniques, and assess their value and limitations for assessing the effects of genetic variants that may be related to human longevity on clinical outcomes and cell functions. Other types of data that could be assessed include information from epidemiologic, clinical, physiologic, or other biologic studies, and results from high throughput screening of compounds that might influence potential targets. The project should also establish a system for its ongoing review of new relevant data, informatics, and methods arising from other sources over the course of the project.

2. Identify and assess gene variant(s) as prospective therapeutic target(s)

Based on the above survey, use selected data sources, informatics resources, and analytic techniques to identify and assess the potential value of specific genetic variants as a potential basis for developing therapeutic target identification strategies. The assessment of the value of variants for this purpose should include consideration of other possible targets in pathways that are influenced by the gene in which the variant is found.

3. Evaluate specific target identification strategies

Based on the results of 1 and 2 above, select at least one such variant (or group of variants) and

evaluate the use of specific investigative methods in a target identification strategy. Investigative

methods that could be considered include:

• Replication studies by analyses of existing population and genetic epidemiologic data.
• De novo human physiologic studies on individuals with and without specific variants.
• In vitro studies to characterize effects of variants on human cellular functions.
• Use of cellular engineering methods such as iPS cell generation or gene editing.
• The project may conduct pilot in vivo or in vitro studies, or analyses of existing databases, as needed for evaluating the feasibility and value of specific methods for this purpose.

Additionally, the project could employ alternate approaches by integrating genetic, genomic, epigenetic, proteomic data to reveal properties that cannot be concluded from studies of individual components. This could involve, for example, combining high-throughput screening tools with computing and modeling tools to derive genomic convergence signals of aging and longevity, or pathway analysis on the identified targets to provide clues on relevant gene networks, biological pathways and key molecules for potential therapeutic targets.

4. Develop preliminary target identification strategies based on one or more specific variants

For each variant (or group of variants) selected and evaluated in 2 and 3 above for which sufficiently feasible and useful investigative methods are available, develop a preliminary target identification strategy that specifies the sequence of studies to be done, and criteria for evaluating results in sequence in regard to decisions regarding choices of further studies in the strategy, discontinuation of the strategy, or the rationale for proceeding to additional steps, such as screening of small molecules for target effects, or evaluation of in vitro or in vivo effects of drugs currently in clinical use that may influence relevant targets.

5. Build a curated bioinformatics resource on prospective targets

Establish a publically accessible data resource identifying information resources surveyed in (1) above, as well as derived data sets developed by the project using such resources. This data resource should also provide documentation of scientific procedures developed and used by the collaborative team.

Support for implementation of studies necessary for full scale validation of therapeutic targets and intervention development based on targets identified by the U24 project could be requested in the future through other grant mechanisms.

New population or family studies on genetic factors influencing longevity are also outside the scope of this FOA.

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.
Application Types Allowed	New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The NIA intends to fund one award corresponding to a total cost of up to $800,000 a year for fiscal year 2014. Future years amounts will depend on annual appropriations.
Award Budget	Direct costs are limited to $450,000 per year (excluding F&A costs on subcontracts.
Award Project Period	Five Years

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

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

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) (formerly CCR) 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.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

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.

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

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Nalini Raghavachari, PhD
Division of Geriatrics and Clinical Gerontology
National Institute on Aging
Gateway Building, Suite 3C307
7201 Wisconsin Avenue
Bethesda MD 20892-9205
(ZIP 20814 for Fed Ex)
Telephone: 301-435-3048
Fax: 301-402-1784
Email: Nalini.raghavachari@nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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.

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

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

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

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

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

Application budgets should include costs for convening up to three, in-person meetings per year in the Washington, DC area. These meetings may involve study-wide meetings, members of the steering committee, external monitoring board (if one is formed), and NIA staff.

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

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

Specific Aims: The application should describe the organization and operational procedures of the collaborative research infrastructure and how the expertise of the members will be integrated and applied to complete planning and preliminary evaluation of a number of potential target identification strategies within the award period. Plans for documentation of key procedures should also be included. The contributions of individual key personnel should be specified.

The application should describe the processes and resources that will be used to identify and evaluate the potential of additional variants over the course of the award including the following:

Applicants should identify specific data resources to be considered including key genomic and population databases, informatics resources, computational tools, in vitro techniques of assessing cellular functional effects of genetic variants, statistical tools, and algorithms useful in assessing human functional effects of variants under consideration.

Systematic ongoing review of human and other data relevant to selection of genetic variants as basis for studies to identify potential therapeutic targets for interventions to extend life span or health span.

Assessment of the value and limitations of the above data sources, including statistical considerations where appropriate.

Research Strategy: For at least one gene variant associated with human health and life span, the application should describe the specific proposed approach to evaluate and develop target identification strategies, including (as appropriate) a plan for preliminary analyses of database information or de novo studies on humans or human cells in vitro, including high-throughput screening of molecules that may mimic phenotypic effects of a favorable variant.

In addition applicants may elect to have an external monitoring board with subject matter expertise in the scientific disciplines in addition to the research team members who can provide guidance as needed to the U24 project. The application should identify that choice in the Approach section of the Research Strategy. The application should identify the expertise appropriate for the monitoring board and the number of members. Applications should not mention names or provide biographical sketches of proposed monitoring board members.

Letters of Support: The application should include letter(s) of support from partnering organization(s) if any, and for demonstrating access to any databases or other resources proposed for use as outlined in the application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

• The application should include plans for sharing of data and any unique research resources that are generated by the project in concordance with NIH policies on the sharing of data and resources. It is expected that resources developed by the U24 will be made available to the broader scientific community.
• The applicant should provide details on the existing resources that are currently available and provide how the publicly available data will be handled and shared among groups for downstream data analysis.
• The applicant should provide the plans for creating a comprehensive and verified database with all the clinical, genotypic and phenotypic information. Mechanism for distribution and access of this database to the scientific community should also be included in the application.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

This initiative is not subject to intergovernmental review.

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.

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 Applying Electronically.

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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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).

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? 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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

How appropriate are the combined skills of the key personnel (from the fields of computational biology, statistics, gerontology, physiology, cell biology, comparative biology and genetics) to execute and implement the proposed research strategies?

If the collaborative team includes other private partnering organization(s), are the relationship and division of work between team members and the partners well defined in the application?

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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the organization and operational procedures of the research infrastructure be effective to plan and perform preliminary evaluation of potential target identification strategies within the five-year award period in a collaborative manner?

Has the applicant provided sufficient information on the nature of the database, and verification of the data for downstream analyses?

Has the applicant provided information on the documentation of key procedures used in the study?

For the studies based on one or more specific variant(s) associated with human longevity, are the proposed approaches to evaluate and develop target identification strategies, and the plans for pilot database or de novo studies, well designed, state of the art and applicable for the purpose?

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?

Does the research environment have appropriate resources at the applicant Institution(s) to accomplish the research objectives of the U24 program, including computational resources, accessibility of databases, informatics and biotechnology for pilot studies and provide a significant contribution for translation of gene variants associated with longevity?

Does the research environment appropriately leverage existing resources at the applicant's Institution(s) to accomplish the research objectives of the U24 program?

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.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six 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 Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. 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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

Not Applicable

Revisions

Not Applicable

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) Genome Wide Association Studies (GWAS).

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.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIA, 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:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• 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 appropriate national Advisory Council or Board. 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.

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.

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

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 grantee’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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees 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 the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

U24 Organizational Components and Responsibilities:

The Program Director /Principal Investigator (PD/PI) will form a multidisciplinary, collaborative research team consisting of expertise in genetics, epidemiology, physiology, gerontology, cell biology, biotechnology, statistics, and bioinformatics from private industries and academic research centers to carry out the research objectives for the U24 project.

A collaborative effort rather than a fee for service type arrangement should be planned. Expertise in strategies for applied and collaborative research, such as those used by pharmaceutical companies in drug development, is also likely to be crucial for the translation of genetic information into therapeutic targets.

The PD(s)/PI(s) will have the primary responsibility for carrying out the planning, organizing and implementation of research activities, day-to-day administrative functions and overall development of the U24 program.

The PD/PI should establish a steering committee (SC) to oversee the activities of the collaborative research team.

The SC will serve as the governing body for the U24 project. It consists of the PD(s)/PI(s) of the U24 and a NIA staff member (one voting). The SC will act collectively to approve planned analyses and/or pilot studies, establish study policies, help resolve issues and policy decisions, and provide direction and guidance to the project. The SC will also act as liaisons to potential industry collaborators, and fill other roles as defined by the project. The SC will meet regularly via teleconferences and periodically have in-person meetings.

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

The NIA Project Scientist will serve as the contact point for all facets of the scientific interaction with the awardee(s). The NIA Project Scientist may also participate in data analyses, interpretations and ensure the public availability of data, findings and related resources developed during the course of the U24 project.

The NIA Project Scientist may serve as co-authors in publications as appropriate (dependent on the amount of involvement in the study) and jointly agreed through the Steering Committee.

NIA will designate additional NIA staff as a Program official to provide advice to the awardee on administrative issues. Additional responsibilities may include communicating with the principal investigator and staff to review fiscal issues, and other relevant matters. The NIA Program Official will also be responsible for attendance at meetings of the SC.

The application must also include a statement indicating the applicant’s willingness to abide by the Cooperative Agreement Terms and Conditions of the Award.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee 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 individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee'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.

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

A final progress report, 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.

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY: 301-451-5936
Email: GrantsInfo@nih.gov

Nalini Raghavachari, PhD
National Institute on Aging
Telephone: 301-435-3048
Email: nalini.raghavachari@nih.gov

Ramesh Vemuri, Ph.D.
National Institute on Aging
Telephone: 301-496-9666
Email: VemuriR@nia.nih.gov

Linda Whipp
National Institute of Aging
Telephone: 301-402-7731
Email: whippl@mail.nih.gov

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.

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 and 45 CFR Parts 74 and 92.