Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization's time zone. 

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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - 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.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of 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. Notice of Funding Opportunity Description

Background

Chemical modifications of RNA have been documented for decades. Only recently, advances in genomic technology have enabled systematic detection and characterization of these modifications, which revitalized the study of RNA modifications and is shaping the field of epitranscriptomics. Over 170 distinct RNA modifications have been discovered, including N⁶-adenosine methylation (m⁶A), N¹-adenosine methylation (m¹A), 5-cytosine methylation (5mC), cytosine to uracil (C-to-U) deamination, pseudouridylation (ψ), ribose 2’O-methylation, and adenosine to inosine (A-to-I) deamination. These post-transcriptional modifications are enzymatically catalyzed by RNA modifying proteins (RMPs) to install (writer), remove (eraser), and interpret (reader) chemical changes in RNA molecules, utilizing a myriad of reactions, such as methylations, deaminations, thiolations, glycosylations, and isomerizations. Increasing evidence, which was substantiated only during the past few years, supports a pivotal role of RNA modifications in the maintenance of health homeostasis and in disease development. There is a growing recognition that RNA modifications and the modification machinery have direct functional effects on gene expression regulation and physiological processes. Dysregulation of RNA processing pathways has been implicated in many diseases, including cancer, cardiovascular diseases, and neurological and neurodegenerative diseases. Emerging evidence indicates that RNA modification is highly regulated in the brain. Dysregulation of RNA modification and its machinery of writers, readers, and erasers is implicated in the etiology of neurodevelopmental and neurodegenerative disorders, including AD. 

Among the various modifications described to date, N6-methyladenosine (m6A) is the most prevalent and abundant internal RNA modification. A growing body of evidence indicates that RNA m6A methylation is critical in many molecular and cellular processes, such as mRNA splicing and translation, RNA stability, DNA damage response, circadian rhythm, neural development and differentiation, and learning and memory. More recently, the expression levels of methylation machinery and m6A levels have been investigated in the context of neurodegenerative diseases. A reduction in neuronal m6A levels was observed in the brains of patients with AD, along with a significant decrease in the expression of m6A methyltransferase like 3 (METTL3), suggesting that m6A dysregulation due to METTL3 reduction may contribute to neurodegeneration in AD. Widespread RNA hypermethylation and m6A modifications were observed in post-mortem samples from ALS patients, with m6A modifications modulating RNA binding by TDP43. Reduction of m6A reader YTHDF2 mitigated TDP43-mediated toxicity in ALS models. Additionally, impaired synaptic protein synthesis was associated with reduced m6A-modified transcripts, indicating that m6A RNA methylation regulates synaptic protein synthesis and may contribute to cognitive decline in aging and AD. Apart from m6A, adenosine-to-inosine (A-to-I) editing is another prevalent type of modification significantly contributing to the global diversity of RNA sequences in the central nervous system and is highly enriched in neuronal and glial cells. These base-specific changes influence splicing patterns, alter the stability of RNA secondary structures, recode proteins, and affect miRNA binding to their targets. A-to-I editing is driven by a family of adenosine deaminases acting on RNA (ADAR) enzymes. Without appropriate RNA editing by ADAR1, endogenous RNA transcripts stimulate cytosolic RNA sensing receptors and activate the interferon inducing signaling pathways, which can cause severe tissue injury and dysfunction. 

Despite these advances, the extent and diversity of different types of RNA modification and their role in molecular and cellular functions in brain and neurodegenerative diseases are largely unexplored. Most efforts so far have been devoted to a few RNA modifications such as m6A and A-to-I editing, and to the discovery of novel RNA modifications. The significance of these epitranscriptomic marks in brain development and neuronal function is just beginning to be appreciated. The variety and prominent roles of RNA modifications in numerous biological processes and functions present exciting opportunities for discovering diagnostic markers and novel mechanistic insights into brain aging and AD/ADRD. 
       
While RNA modification is emerging as a new avenue for therapeutics and biomarkers, the dynamic regulation of RNA modifications and the modification machinery, their functional roles, and their relationship with aging and pathogenesis of AD/ADRD remains to be elucidated. Uncovering mechanistic insights underlying the dysregulation of RNA modifications and the impact on cellular and pathophysiological processes will reveal novel functional readouts and targets to fine-tune gene regulation and better understand brain aging and disease heterogeneity. Such insights will inform new strategies for estimating AD risk, predicting disease trajectory, and enabling drug development. This will ultimately pave the way toward precision medicine for AD/ADRD.
 

Program Scope and Research Objectives

The purpose of this NOFO is to catalyze innovative research to elucidate the molecular landscape and functional implications of RNA modifications in brain aging and AD/ADRD. AD-related dementias include Lewy body dementia (LBD), frontotemporal dementia (FTD), vascular cognitive impairment/dementia (VCI/D), and mixed dementias. This NOFO utilizes the Exploratory/Developmental Grant (R21) mechanism, which supports high-risk, exploratory research projects that propose novel scientific ideas, approaches, or technologies to discover functional roles of RNA modifications and the underlying mechanisms involved in brain aging and the pathogenesis and progression of AD/ADRD. R21 applications are designed to establish proof-of-principle and generate key data for future hypothesis-driven applications. Proposed studies should focus on functional characterization and mechanistic investigation of previously identified RNA modifications. 

Specific research areas that are of great interest include, but are not limited to, the following:
 

• Identify functionally relevant RNA modification sites and genes linked to AD onset and severity across multiple brain regions and cell types. Dissect tissue- and cell-specific epitranscriptome-induced biological changes.
• Investigate temporal and spatial dynamics of RNA modifications driving brain aging and AD/ADRD. Elucidate the role of these modifications in signaling pathways and pathophysiological processes.
• Characterize RNA modifying machinery including writers, readers, and erasers, and identify the cellular and subcellular location and function of these proteins during brain aging and over the development of AD/ADRD.
• Dissect the cellular and molecular mechanisms of RNA modifications associated with the onset, progression, and severity of AD/ADRD and in brain aging. Examine the relationships between RNA modifications and AD vulnerability. Identify potential therapeutic targets.
• Elucidate the interplay between different RNA modifications and RNA modifying proteins, and their functional roles.
• Identify RNA modification signatures that can serve as potential biomarkers for disease onset, progression, and severity.
• Explore therapeutic interventions interfering with RNA modifications and RNA modifying protein-mediated molecular pathways and cellular processes.
• Develop novel in vitro, in vivo, and in silico methodologies and tools for the detection, quantification, and examination of functional impact of RNA modifications in the brain and AD/ADRD.

This program will operate under open-science principles. All data and analytical outputs will be shared rapidly and broadly via the NIA-supported AD Knowledge Portal.

This NOFO runs parallel with RFA-AG-25-022, a NOFO with a similar scientific scope that utilizes the Research Project Grant (R01) mechanism. As an R01 NOFO, RFA-AG-25-022 supports mature research projects that are hypothesis-driven with strong preliminary data. Prospective applicants are encouraged to contact the scientific and research contact for this NOFO to determine whether their proposed research best fits with the R21 mechanism or the R01 mechanism.

Non-Responsiveness Criteria

The following types of applications will be considered non-responsive and will be withdrawn prior to review:

• Applications that primarily focus on computational analysis and/or modeling of existing data sets, with limited effort on experimental characterization of RNA modifications.
• Applications that primarily conduct molecular profiling to discover RNA modifications but do not investigate the functional impact of RNA modifications on disease.
• Applications that study RNA splicing or RNA metabolism.
• Applications that focus on developing in vitro, in vivo, or in silico methodologies and tools for detecting RNA modifications without experimental characterization of RNA modifications.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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)

Local 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)

Federal Governments

• 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 Organizations)

Non-domestic (non-U.S.) Entities (Foreign Organizations) are 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

The applicant organization must be registered in SAM.gov, Grants.gov, and eRA Commons before submitting an application.

While applicants can review the requirements and start developing applications before registrations are complete, applicants should complete these steps early.

Failure to complete required registrations before the due date is not a valid reason for a late submission. Please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for more information.

• System for Award Management (SAM) – Applicant organizations must have an active account with SAM.gov. This includes having a Unique Entity Identifier (UEI). SAM.gov registration can take 6 weeks or longer. Begin that process today. To register, go to SAM.gov Entity Registration and select Get Started. Select the Entity Registration Checklist on the same page to view a list of the information needed to need to register. Organizations must maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. After registering in SAM, organizations can register with Grants.gov and eRA Commons.
  • 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.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; 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. Make sure the organization uses the same UEI on the application, in SAM.gov, and in eRA Commons.
• Grants.gov – Applicant organizations must also have an active account with Grants.gov. See step-by-step instructions at the Grants.gov Quick Start Guide for Applicants. 

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

Every 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.

All other personnel listed on the SF424 (R&R) Senior/Key Person Profile must have an eRA Commons account. 

• NIH invites anyone who has the skills, knowledge, and resources needed to carry out the proposed research as a program director or principal investigator (PD/PI) to work through their organization to apply. 
• Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.
• For institutions and organizations who are proposing multiple PDs/PIs, visit the Senior/Key Person Profile (Expanded) component of the Research Instructions and look for submission details.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application if each is scientifically distinct.NIH will not accept duplicate or highly overlapping applications under review at the same time. See the policy on Submission of Resubmission Application.

This means that NIH will not accept:

• A new (A0) application submitted before NIH issues the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application submitted before NIH issues 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 the policy on  Similar, Essentially Identical, or Identical Applications.

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 NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

Applicants must follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide unless this NOFO says otherwise. NIH strictly enforces these requirements. If the applicant does not follow them, NIH may delay or not accept the application for review. NIH encourages organizations to submit applications in advance of deadlines.

Letter of Intent

NIH asks that applicant organizations let us know if they plan to apply for this opportunity. The purpose is to plan for the number of expert reviewers needed to evaluate applications. It is not required.

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
• The funding opportunity number and title
• Participating institution(s)
• The name, phone number, and email address of all the PD(s)/PI(s)
• Names of other key personnel

Please email the optional letter of intent to:

Alison Yao, Ph.D.  
National Institute on Aging (NIA)  
Division of Neuroscience (DN)  
Telephone: 301-827-7264  
Email: yaoal@nia.nih.gov   

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed.

R&R or Modular Budget

All instructions in the How to Apply - Application Guide must be followed.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• This program will operate under open-science principles. All data and analytical outputs will be shared rapidly and broadly via the NIA-supported AD Knowledge Portal.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

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 How to Apply - Application Guide, with the following additional instructions:

If the answer to the question “Are Human Subjects Involved?” on the R&R Other Project Information form is yes, include at least one human subjects study record. Use either of the following parts of the PHS Human Subjects and Clinical Trials Information form:

• Study Record
• Delayed Onset Study

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset is not the same as a delayed start study that can be described but will not start immediately.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply Application Guide.

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

See Part 2. 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. contains information about Key Dates and times. Applicants should apply early to allow time to make corrections to errors found in the application during the submission process before the due date.  When a due 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply – 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.
• NIH allows pre-award costs only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - 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. Follow the overall instructions at How to Submit, Track and View Your Application on our website.

If you encounter a system issue beyond your control that impacts the ability to complete the submission process on-time, 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 have an eRA Commons account that is affiliated 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.

All other personnel listed on the SF424 (R&R) Senior/Key Person Profile must have an eRA Commons account. 

See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - 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 NIA, 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 NIA Referral Office by email at ramesh.vemuri@nih.gov when the application has been submitted. Please include the NOFO 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

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.

For this particular NOFO, note the following:
 

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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.

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.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIA, in accordance with NIH peer review policies and practices, 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.

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.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Before making an award, NIH conducts a pre-award risk assessment. The purpose is to make sure the applicant organization has handled any past federal awards well and demonstrated sound business practices. NIH uses SAM.gov Exclusions and Responsibility / Qualification to check this history for all awards likely to be over $250K. This provision will apply to all NIH grants and cooperative agreements except fellowships.

The applicant organization can comment on the information in SAM.gov. NIH will consider the comments before making a decision about level of risk.

If there is a significant risk, NIH may choose not to fund the application or to place specific conditions on the award.

For more details, see 2 CFR Part 200.206.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access their 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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

If an application is successful, NIH will email a Notice of Award (NoA) to the authorized official. NIH will inform the applicant organization if their application is disqualified or unsuccessful.

The NoA is the only official award document. The NoA explains the amount of the award, important dates, and the terms and conditions recipients need to follow. Until the organization receives the NoA, the recipient does not have permission to begin the research project.

All awards are subject to terms and conditions at Award Conditions and Information for NIH Grants website. 

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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 terms and conditions in the Notice of Award (NoA) The NoA includes the requirements of this NOFO. For these terms, note the following:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.
• Recipients must follow all applicable nondiscrimination laws. Recipients agree to this when registering in SAM.gov. The recipient must have a one-time Assurance of Compliance (HHS-690) on file with the HHS Office of Civil Rights. To learn more, see the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Not Applicable

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

eRA Service Desk 

Contact eRA Service Desk for questions about ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues.

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information 

Contact Grants Information for questions about application instructions, application processes, and NIH grant resources.
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support 

Contact Grants Information for questions about Grants.gov registration and Workspace.
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Alison Yao, Ph.D.
National Institute on Aging (NIA)
Division of Neuroscience (DN)
Telephone: 301-827-7264
Email: yaoal@nia.nih.gov

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-402-7700
Email: ramesh.vemuri@nih.gov

Jeni Militano
National Institute on Aging (NIA)
Telephone: 301-827-4020
Email: jeni.militano@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.

NIH makes awards 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 2 CFR Part 200.