Part 1. Overview Information

Key Dates

All applications are due 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.

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.

IMPORTANT: Per NOT-OD-24-086 updated application forms (FORMS-I) will be used for this opportunity. The updated forms are not yet available and will be posted 30 calendar days or more prior to the first application due date. Once posted, you will be able to access the forms using one of the following submission options:

1. NIH ASSIST
2. An institutional system-to-system (S2S) solution
3. Grants.gov Workspace

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Overview: Multiple consortia, both NIH and non-NIH supported, are generating large scale transcriptomic and epigenomic data at the single cell/nucleus level from human brain tissue. Efforts at the BRAIN Initiative, including BICCN and BICAN, are establishing public reference atlases of cell types in “normal” human brain, while other large-scale studies aim to query cell-type specific changes at the single cell level in disease (for example: SEA-AD, AMP-AD, AMP-PD, SCORCH, PsychENCODE). In many cases, the raw datasets being produced are accessible to only the consortium members, and the processed, clustered, and annotated data remain explorable by the public in a largely fragmented and unintegrated fashion, if at all.

Objective: The award made via this pilot program will establish an integrated resource that allows users to explore, analyze, and download processed de-identified human brain single-cell transcriptomics and epigenomics data harmonized across reference and disease datasets. Further, the recipient will provide a federated one-stop hub to access underlying raw datasets. The recipient will enlist the collaboration of at least three major existing data archives housing NIH generated datasets, ingest raw or processed data, harmonize datasets as needed, and develop a dashboard of online exploration and discovery tools. Based on the combined datasets, the recipient will create a unified cell-type taxonomy by brain region and an accompanying, community annotatable, draft cell-type nomenclature.

In addition, the recipient will work with NIH single cell consortia to develop shareable data harmonization tools, data standards, and cell type annotation and curation platforms. This effort will pilot a sustainable centralized platform for the joint analysis and exploration of NIH generated single-cell omics data, laying the groundwork for the development of community-supported human brain single-cell knowledgebases across broad disease states.

Explorer development deliverables are expected to include, but are not limited to the following portal components and functionalities:

• Single Cell Genomics Explorer will integrate all relevant dataset-specific metadata into the explorable, user-facing dataset.
• Single Cell Genomics Explorer will integrate all relevant single-cell level metadata into the explorable, user-facing dataset.
• Harmonization of datasets across datatypes and level of analysis, and provision of harmonization tools to the community.
• Minimal Explorer functionality will allow users to explore and map all cells in 2D expression/accessibility space.
• Data modalities: The Explorer functionality is to be focused on single-cell and/or single-nucleus transcriptomic or epigenomic data from human post-mortem brain tissue.
• The Explorer Knowledgebase will include a unified cell-type taxonomy and a draft, curatable cell typed nomenclature.
• Development of metrics to evaluate Explorer use by, and utility to, the community.

Additional requirements: The recipient will integrate at least three (3) major NIH-supported human single-cell omics datasets (preferably consortia generated), one of which is the combined human BICCN/BICAN human omics dataset (NEMO), while ensuring that all raw and processed data used is findable by the community.

Non-Responsiveness Criteria

The following types of applications will be considered non-responsive to this NOFO and will be administratively withdrawn prior to scientific peer review.  Applications that:

• Generate new primary data from biospecimens.
• Include data not obtained from human specimens.
• Do not focus on the harmonization and annotation of single-cell and single-nucleus transcriptomics or epigenomics data.
• Do not propose to integrate datasets found in NEMO with at least two other major NIH-supported datasets.

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

All organizations administering an eligible parent award may apply for a supplement under this NOFO.

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 Government

• 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 (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

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - 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. Failure to complete registrations in advance of a 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 additional information. 

• 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.
  • 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 registration; 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 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.

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 their organization to develop an application for support. 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 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the 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, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 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

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

Letter of Intent

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:

Daniel Miller
Email:[email protected]
Telephone: 301-469-1853

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.

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

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

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

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

R&R 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.

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

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

Applicants are expected to propose a research strategy to achieve the goals of the NOFO, which must address the following:

Metadata integration in the Single Cell Genomics Explorer:

• Describe how the Single Cell Genomics Explorer will achieve integration of the following dataset-specific metadata into the explorable, user-facing dataset:
  • Location of source dataset
  • Minimal phenotypic metadata of tissue donor (demographics, clinical diagnosis, neuropathologic data, tissue QC metrics)
  • Data generation platform, instrumentation, and QC metrics (number of cells, etc)
• Describe how the Single Cell Genomics Explorer will achieve integration of the following single-cell level metadata into the explorable, user-facing dataset:
  • Anatomical location based on established widely accepted human brain atlases (for example, Allen Common Coordinate Framework)
  • Single cell omics QC data (read depth, length, etc)

Harmonization of datatypes:

• Detail how the datasets will be harmonized across all datatypes (metadata, sequencing data) and across all relevant levels of analysis, including QC and alignment of fastq files to reference genome; generation of gene matrix data, and umaps.
• Describe how the processing and harmonization tools will be made available to the community, for example in a “Tools” tab.

Minimum level of Explorer functionality available to users:

• Describe how the functionality will be developed to enable users to do the following:
  • Explore and map all cells in 2D expression/accessibility space, by dataset, by phenotype, and in parallel to do the following:
    • Select cells graphically to visualize summary information (e.g. expression data and disease state)
    • Download umap data from select datasets by cell-types.
  • Map external datasets (by submitting cell/gene matrices) onto resource-internal cell type data.
  • Download cell-level gene expression counts, query umap data by cell type, and generate summary of cell type specific gene expression markers.

Data modalities:

• Provide details on the single-cell and/or single-nucleus transcriptomic or epigenomic data from human post-mortem brain tissue.
• If proposing the inclusion of bulk RNA sequencing data, epigenomic, DNA sequencing and variant data, or data from tissue that is not human post-mortem (i.e. hIPSCs, etc), explain how these datasets will serve to enhance the quality and biological significance of the single-cell and single-nucleus data.

Explorer Knowledgebase:

• Describe how the resource generates an explorable unified taxonomy across integrated cell types and by anatomical brain location.
• Explain how a draft nomenclature will be generated based on the above taxonomy. Explain methods of curation, both by the awardee and the community. Describe how the awardee will provide a platform for community-input based curation, regarding refined cell-type information, transmitter types, function (such as inhibitory, excitatory, etc), and anatomical location.

Development of use and utility metrics:

• Provide details on how the platform will provide a built-in mechanism to track frequency of community interaction with the portal: visit, query, export numbers, as well rate of community-based annotation.
• Explain the mechanisms for user feedback on portal performance that are quantifiable.

Additional requirements:

• Provide details on how to achieve integration of at least three (3) major NIH-supported human single-cell omics datasets (preferably consortia generated), one of which must be from the BRAIN Initiative (NEMO).
• Explain how the proposed resource will enable the specified datasets to become more findable, accessible, interoperable, and reusable (FAIR).
• Describe how all raw and processed data will be findable by the community, and how processing tools will be usable by the community to harmonize and analyze datasets.
• Describe why integration of these specific NIH-supported human single-cell omics datasets is important to advance the field of neuroscience.
• Describe how the resources  will be disseminated  to the community.
• Explain flexibilities in the research plan that enable additional datasets to be incorporated based on needs and opportunities that arise in consultation with NIH staff.
• Letters of support: Letter of support or letters of collaboration from the PI of each proposed data consortium is strongly encouraged.
• Annual Milestones: Provide annual milestones with clear outcomes and actionable criteria for evaluating progress and decisions on project continuation and direction. Include plans for ongoing feedback and critical evaluation by NIH Program Staff.

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):

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.

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

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 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 How to Apply - 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 How to Apply - Application Guide must be followed.

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 SF424 (R&R) 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

Part I. 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 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.

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 Section 7.9.1 Selected Items of Cost.

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. 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 form. 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 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 components of participating organizations at NIH. Applications that are incomplete, non-compliant, and/or nonresponsive will not be reviewed.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected]. 

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 announcement, note the following:

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 proposed Resource address the needs of the research community that it will serve? Is the scope of activities proposed for the Resource appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research community.

Specific to this NOFO:

• To what extent will the integration of the specified NIH-supported human single-cell omics datasets advance the field of neuroscience?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the resource? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing data science research? Do the investigators demonstrate significant experience with coordinating collaborative data science research? If the center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the resource? Does the applicant have experience overseeing selection and management of subawards, if needed?

Specific to this NOFO:

• Are the PD/PI and other key personnel devoting sufficient time and effort to achieve the goals? 

Innovation

Does the application propose novel tools or approaches in coordinating the research datasets from NIH programs and enabling their use by the broader community that the Resource will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of data science approaches proposed?

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research community the Resource will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the Resource, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the resource is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the Resource? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

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?

Specific to this NOFO:

• How feasible is the proposed approach to harmonize the specified single-cell datasets and associated metadata?
• To what extent do the Explorer functionalities allow users to explore and map the harmonized datasets?
• How well does the Explorer enable users to explore and map all cells in 2D expression/accessibility space, by dataset, by phenotype, and in parallel, to (1) select cells graphically to visualize summary information (e.g. expression data and disease state) and (2) download umap data from select datasets by cell types?
• How effectively does the Explorer allow users to map external datasets (by submitting cell/gene matrices) onto resource-internal cell type data?
• To what extent does the Explorer enable users to download cell-level gene expression counts, query umap data by cell type, and generate summaries of cell type specific gene expression markers?
• How well does the resource generate an explorable unified taxonomy across integrated cell types and by anatomical brain location?
• To what extent will the proposed use and utility metrics track frequency of community interaction with the portal and enable user feedback on portal performance?
• How well do the proposed resources enable the raw and processed datasets to become findable, accessible, interoperable, and reusable (FAIR)?
• How broadly will the resource be disseminated to the community?
• How flexible is the research plan to enable additional datasets to be incorporated based on needs and opportunities that arise?
• How well do the milestones provide clear outcomes and actionable criteria for evaluating progress and decisions on continuation and project direction?
• How feasible is the plan to integrate at least three (3) major NIH-supported human single cell omics datasets (preferably consortia generated), one of which must be from the BRAIN Initiative (NEMO)?

Environment

Will the institutional environment in which the Resource will operate contribute to the probability of success in facilitating the research community it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Resource proposed? Will the Resource benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

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.

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 three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals 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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

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

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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 Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For [programs/projects/networks/consortia/resources] 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 NINDS, 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.

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 NOFO. 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.

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.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

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

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• 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.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by 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. 

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 (HHS) grant administration regulations at 2 CFR Part 200, 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 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• Retain the primary authority and responsibility for the project as a whole and development of the methods, procedures to accomplish the aims and objectives of the NOFO, and preparation of publications.
• Develop milestones with specific timelines and criteria for evaluation, and making appropriate revisions based on the feedback from the Principal Investigator meetings and recommendations from NIH Staff.
• Provide, in addition to standard annual progress reports, other relevant information to NIH Staff, and coordinate and cooperate with NIH staff and other members of appropriate collaborating NIH programs.
• Keep NIH Staff apprised of any potential impediments to execution of the goals of the Project.
• Work directly with NIH Staff on the coordination of intra-program activities between relevant NIH programs.
• Participate in the appropriate coordinating meetings, working groups, and/or teleconferences as needed.
• Recipients 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 HHS, PHS, and NIH policies.

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

• Provide technical assistance and advice to the awardee as appropriate to achieve the aims of the cooperative agreement.
• Help guide prioritization of data and knowledgebase functionality development.
• Consult on datatypes selected to be ingested, including the discussion and prioritization of datasets and datatypes to be potentially added during the duration of the award, as budget allows.
• Serve as liaison between awardees and the BRAIN initiative program staff and the NIH awarded BICAN data archives.
• Participate in organizing an “Explorer show-and-tell meeting” with Blueprint and BRAIN community members to showcase the resource at the conclusion of the project period.
• Develop working groups and trans-project efforts as needed to ensure alignment with BRAIN and Blueprint efforts.
• Monitor the progress of the Research Project, help coordinate research approaches, and contribute to the shaping of the project or approaches as warranted. NIH Staff will support and facilitate this process but will not direct it.
• Assess and negotiate initial milestones with specific timelines and criteria for evaluation, and make appropriate revisions based on the feedback from the Principal Investigator meetings and recommendations from NIH Staff.
• Retain the option to recommend the withholding or reduction of support from any cooperative agreement that substantially fails to achieve its goals according to the milestones agreed to at the time of the award or fails to comply with the Terms and Conditions of the award.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
• Areas of Joint Responsibility include:
• Convene to assess progress, discuss data resources, establish priorities, consider policy recommendations, and discuss strategies.
• Meet in person, virtually, or by teleconference, with additional project staff and/or NIH staff, on a schedule to be determined.

Areas of Joint Responsibility include:

• NIH staff and PI will convene regularly in person, virtually, or by teleconference, with additional project staff and/or NIH staff, on a schedule to be determined, to assess progress, discuss data resources, establish priorities, consider policy recommendations, and discuss strategies.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 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 HHS regulation 45 CFR Part 16.

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 (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: https://www.era.nih.gov/need-help (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: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Daniel Miller
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1853
Email: [email protected]

Erin E. Gray, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-451-3968
Email: [email protected]

Deborah Henken, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Telephone: 301-496-5541
Email: [email protected] 

Guoying Liu Ph.D.
National Institute of Biomedical Imaging and Bioengineering 
301-594-5220
[email protected]

Changhai Cui, PhD
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-1678
Email: [email protected]

Emrin Horgusluoglu, Ph.D.
National Center for Complementary & Integrative Health (NCCIH)
Phone: 240-383-5302
Email: [email protected] 

David Panchision, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-402-3969
Email: [email protected]

Melissa Ghim, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-529-6570
Email: [email protected]

Cheri Wiggs
NEI - NATIONAL EYE INSTITUTE
Phone: (301) 402-0276
E-mail: [email protected]

John Satterlee, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1020
Email:[email protected]

Jonathan Hollander, PhD
NIEHS – National Institute of Environmental Health Sciences
Phone: 984-287-3269 or 919-698-7004
Email: [email protected]

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email:[email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [email protected]

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected] 

Heather Weiss
National Institute of Mental Health (NIMH)
Telephone: 301-443-4415
Email: [email protected] 

Gabriel Hidalgo
National Institute of Dental and Craniofacial Research (NIDCR)
Phone: 301-827-4630
E-mail: [email protected]

Karen Robinson Smith
NEI - NATIONAL EYE INSTITUTE
Phone: 301-435-8178
E-mail: [email protected]

Ericka Wells
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-6705
Email: [email protected]

Jenny Greer,
NIEHS – National Institute of Environment Health Sciences
Phone: 984-287-3332 or 919-892-4180
Email: [email protected]

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.

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 2 CFR Part 200.