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

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

Background

Since 2014, the Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative has aimed to accelerate the development and application of innovative neurotechnologies, enabling researchers to produce a new dynamic picture of the brain that reveals how individual cells and complex neural circuits interact in both time and space. It is expected that these advances will ultimately lead to new ways to treat and prevent brain disorders.

As one of several federal agencies involved in the BRAIN Initiative, NIH's contributions to the BRAIN initiative were initially guided by "BRAIN 2025: A Scientific Vision," a strategic plan that detailed seven high-priority research areas. This plan was updated and enhanced in 2019 by: "The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures" and "The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society." This and other BRAIN Initiative Notices of Funding Opportunity (NOFOs) are based on this vision and issued with input from Advisory Councils of the 10 NIH Institutes and Centers supporting the BRAIN Initiative, as assisted by the NIH BRAIN Multi-Council Working Group.

The NIH BRAIN Initiative recognizes that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogeneous teams. There are many benefits that flow from a diverse scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

To support the best science, the NIH BRAIN Initiative encourages inclusivity in research. Examples of structures that promote diverse perspectives include but are not limited to:

• Transdisciplinary research projects and collaborations among neuroscientists and researchers from fields such as computational biology, physics, engineering, mathematics, computer and data sciences, as well as bioethics.
• Engagement from different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Individual applications and partnerships that enhance geographic and regional heterogeneity.
• Investigators and teams composed of researchers at different career stages.
• Participation of individuals from diverse backgrounds, including groups traditionally underrepresented in the biomedical, behavioral, and clinical research workforce (see NOT-OD-20-031), such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Project-based opportunities to enhance the research environment to benefit early- and mid-career investigators.

The NIH also encourages businesses to participate in the BRAIN Initiative. It is possible for companies to submit applications directly to BRAIN Initiative program announcements or to collaborate with academic researchers in joint submissions. Small businesses should consider applying to one of the BRAIN Initiative small business NOFOs.

The BRAIN Initiative requires a high level of coordination and sharing between investigators. It is expected that BRAIN Initiative recipients will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings and in other activities such as the annual PI meeting. The data sharing expectations for BRAIN Initiative awards can be found at NOT-MH-19-010.

This NOFO is related to the transformative project, "A Cell Type-Specific Armamentarium for Understanding Brain Function and Dysfunction," described in the "The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures" report of the Advisory Committee to the NIH Director BRAIN Initiative Working Group 2.0.

Scaled Production and Distribution Facilities for Brain Cell-Type Specific Access Reagents

Recent progress in experimental neuroscience has been driven by new methods and technologies. These have in turn inspired new discoveries and hypotheses. Among new technologies are reagents to access and manipulate specific brain cell types in experimental animals and human ex vivo tissue and cells (e.g., adeno-associated viral (AAV) vectors, lentiviral (LV) vectors, rabies viral vectors, nanoparticles, improved transgenic engineering methods, molecular sensors of neural activity, optogenetic and chemogenetic effector proteins, gene editors). These molecular and genetic tools enable the dissection of neural circuit function through the precise delivery of mapping, monitoring, and manipulation reagents. Novel reagents have enabled the detailed study of neural activity with sub-second timing and across thousands of individual neurons in behaving animals. A dynamic and detailed picture of the brain in relation to behaviors has started to emerge.

Increasing numbers of brain cell types are being defined based on comprehensive transcriptomic, epigenomic, and anatomical profiling. Significant progress has been made in defining this diversity through a census of mammalian brain cell types, supported by the BRAIN Initiative Cell Census program. The BRAIN Initiative Cell Census effort was initiated in 2014 to define a brain parts list with unprecedented detail through molecular and anatomical profiling of the mouse, non-human primate, and human brain. By 2023, the program together with other efforts succeeded, for example, in defining nearly 5000 cell types in the mouse brain with transcriptomic and anatomical position information. Many more brain cell types have been and will continue to be delineated in other mammalian species including humans.

The BRAIN Initiative Armamentarium project intends to leverage this brain cell type information to create molecular or genetic access reagents to deliver mapping, monitoring, and manipulation payloads to distinct circuit components. The intention is for the breadth of Armamentarium project reagents to transform the dissection of neural circuits underlying behavior by experimental neuroscientists.  The Armamentarium project is conceptually aimed at enabling unique access to each molecularly defined brain neural cell type that could exhibit a distinct cellular, circuit, or behavioral function. The BRAIN Initiative Armamentarium project began with 8 awards made in 2021-2023 under RFA-MH-20-556 and RFA-MH-21-180.  These initial awards formed the Armamentarium Consortium.  The initial goal of the consortium was to evaluate scalable molecular genetic technologies, production, and distribution for cell type-selective reagents across several vertebrate species. Scalable technologies were established by pilot projects in several areas, including: improved gene regulatory element discovery, engineering of more selective viral vector tropism, multiplexed screening for specific enhancers and minimally invasive viruses in various species, novel RNA editing-based and microRNA control strategies, and higher throughput in situ hybridization validation methods.

Based on this progress, the Armamentarium project is supporting further scale up of cell type-selective access by Reagent Resources for Design and Development (RRDDs) through RFA-MH-25-100. This NOFO is intended to support scaled Production and Distribution Facilities (PDFs) to disseminate the reagents specifically from the RRDDs to neuroscience researchers.  Widespread deployment of these scaled reagents is a critical step for facilitating functional circuit dissection.  Many different cell types will become genetically accessible with the new reagents. This is particularly important for understanding circuits in less genetically tractable species, like non-human primates.  Augmenting the scale of production and distribution is needed to disseminate the Armamentarium reagents to experimental neuroscience researchers.

Resource Objectives

The purpose of this NOFO is to support PDFs to scale up production and distribution of hundreds of brain cell type-selective access reagents for several vertebrate species, including human ex vivo tissue and cells, developed specifically by Armamentarium RRDD projects for use by neuroscience researchers.  PDFs supported by this NOFO must execute 4 main functions. First, the PDFs must interface specifically with the Armamentarium RRDD project investigators (recipients of RFA-MH-25-100), who will design, validate, and catalogue brain cell type-selective access reagents for several vertebrate species, including ex vivo human tissue and cells. RRDD projects will also adapt the reagents into easily disseminable formats (e.g., DNA proviral constructs for viruses) that can be readily transferred to PDFs for distribution to neuroscience researchers. Second, the facilities must conduct scaled-up production of the RRDD designed and validated reagents. Third, the facilities must disseminate RRDD reagents to neuroscience research users. Fourth, to aid reagent dissemination through distribution of reagent characterization data, the facilities must coordinate RRDD reagent data and metadata distribution to BRAIN Initiative data archives and other archives, neuroscience researchers, and the Armamentarium Consortium members.  Specific goals for areas 1-4 are:

1. Interfacing with Armamentarium RRDDs

Each facility must work with at least one Armamentarium RRDD. In terms of this interface between PDFs and RRDDs, the goal of this NOFO is to support PDFs that:

•  Receive all validated reagent designs, reagent templates, and/or seed reagents from the RRDD partner(s) that were made under RFA-MH-25-100.  
• Improve the reagents, optimize the scaling up of reagent production, and/or further catalogue the reagents. 
• Produce reagents that could include but are not limited to viral vectors, nucleic acid constructs, and nanoparticles designed for selective access to and manipulation of brain cell types. The reagent types for production will depend on the nature and progress of the RRDD projects. NIH will facilitate additional collaborations with the RFA-MH-25-100 recipients to coordinate production and distribution of reagent types as appropriate through a research consortium (see further below).

2. Scaled-up Reagent Production

Each facility must scale up production of all the validated reagents from one or more RRDDs. In terms of this scaling up of reagent production, this NOFO is intended to support PDFs that:

• Scale up reagent production for hundreds of reagents and a variety of reagent unit quantities for use in several vertebrate species, including mice, non-human primates, and human ex vivo tissue and cells.
• Incorporate robust quality control  for reagents and quality assurance for production processes.
• Characterize, formulate, evaluate, and validate the efficacy, reproducibility, stability, activity, and unique characteristics of the produced reagents.
• Ensure purified reagents are safe and appropriate for use in animals and/or human ex vivo tissue and cells.
• Manufacture reagents for the minimal inventory for distribution. Neuroscience research users requesting reagents will pay for future production costs.

3. Disseminating Reagents to Neuroscience Researchers

Each facility must disseminate the scaled-up product inventory to neuroscience research users as broadly as possible. In terms of this dissemination, the goal of this NOFO is to support PDFs that:

• Make and maintain reagent catalogues that are widely accessible.
• Deliver reagents to users.
• Assess the ongoing user demand for various reagents as well as to receive and incorporate constructive user feedback.  User feedback could include information on reagent performance, quality, quantity, timeliness, ordering processes, delivery, cost, feature requests, and related issues.
• Create a website to achieve the above user interface objectives.
• Conduct reagent storage, inventory management, and domestic and international distribution activities.  The management and oversight of distribution activities could include, but are not limited to, material transfer and licensing agreements, webhosting, and recovery of production and distribution costs.
• Include project management efforts for distribution of hundreds of validated reagents from one or more RRDDs at the facility.
• Recover reagent shipping costs paid by neuroscience research requestors.

4. Reagent Data Coordination

Facilities must coordinate RRDD reagent data and metadata distribution to BRAIN Initiative data archives and other archives, neuroscience researchers, and the Armamentarium Consortium members. Overall, Armamentarium reagent data are distributed at 4 venues: (A) BRAIN Initiative data archives (mainly for secondary analysis of these data by others), (B) PDF reagent catalogues where neuroscience research users can obtain reagents, (C) catalogues/atlases with detailed reagent expression data created at the RRDDs, and (D) meetings that include the Armamentarium Steering Group meetings for Armamentarium Consortium members. In terms of the reagent data coordination, the goal of this NOFO is to support PDFs that:

• Ensure that all RRDD project data and metadata for reagent engineering and validation are deposited in a timely manner at (A) according to the BRAIN Initiative Data Sharing Policy.
• Ensure that accessible interfaces are maintained to link (B) to (C).
• Ensure that accessible interfaces are maintained to link (B) to (A).
• Organize (D) to facilitate communication within the consortium about reagent data.

Working Together in the Armamentarium Consortium

Supported projects are expected to work closely together and benefit from membership in the Armamentarium Consortium of researchers, including other Armamentarium recipients from this NOFO, RFA-MH-20-556, RFA-MH-21-180, RFA-MH-22-245, and RFA-MH-25-100. Coordination among consortium members is expected to include sharing of technologies, reagents, and data to improve brain cell type-selective access reagents, as well as cooperation in publication and reagent distribution to integrate the best technologies into neuroscience research. This consortium is expected to include tool developers and disseminators funded by several Armamentarium efforts for brain cell access reagent engineering, reagent production and distribution, and optimization of high-impact reagents for monitoring and manipulating brain cell activity.  The consortium will hold regular meetings (in-person and via videoconference) and conduct other coordinated activities within the consortium as well as in the BRAIN Initiative more broadly.

Milestones and Timeline

Because this NOFO supports scaled PDFs, it is expected that facilities will have scaled up production and distribution goals.  Applications must include proposed milestones and a proposed timeline. Final versions of each will be agreed upon at the time of award. The proposed milestones and timeline should explain critical indicators of progress for the interfacing with RRDDs, scaled-up reagent production, disseminating reagents, and reagent data coordination. The final agreed upon and approved milestones will be specified in the Notice of Award. If justified, future year milestones may be revised based on data and information obtained in the current year. 

Plan for Enhancing Diverse Perspectives (PEDP)

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as described in NOT-MH-21-310, submitted as Other Project Information as an attachment (see Section IV).

Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material. The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.

Examples of responsive research activities include, but are not limited to:

1. Interfacing with Armamentarium RRDD projects:

• Receiving all the validated reagent designs, templates, and/or seed reagents from one or more Armamentarium RRDDs made under RFA-MH-25-100.
• Transfer of large collections of DNA plasmids encoding proviral or transgenic sequences for cell type-selective access reagents.
• Receiving reagent production protocols, cell lines, and/or other unique materials needed for manufacturing.
• Feedback to RRDD projects on produced viral particle titer levels to help improve reagent designs to facilitate large-scale production and use.
• Communication with RRDD projects to harmonize reagent nomenclature with the catalogue made available to neuroscience researchers to obtain reagents.

2. Scaled-up Armamentarium RRDD Reagent Production.  Validated reagents from Armamentarium RRDD projects to be produced at high scale could include:

• Adeno-associated viral (AAV) or lentiviral (LV) vectors containing transcriptional regulatory elements that enable selective or specific expression of neural activity monitoring or manipulation payloads in molecularly defined brain cell types that could have functional relevance.
• Reagents related to scalable use of somatic cell, CRISPR gene editing to knock in monitoring or manipulation constructs to a collection of gene loci that contain cis regulatory elements that drive expression in specific brain cell types.
• AAV capsid variants to selectively transduce brain neural cell types.
• Lipid nanoparticles containing surface proteins that mediate selective transduction of brain neural cell types with genetic constructs.
• LV vectors pseudotyped with antibody or nanobody proteins to mediate selective transduction of brain neural cell types targeting cell surface antigens.
• Transgenic mouse, rat, zebrafish, or other vertebrate responder lines containing widely used reporter, monitoring, or manipulation constructs that can be combined with molecular access driver reagents to be expressed in specific brain neural cell types.
• Transgenic or genome engineered animals having knock in reporter, monitoring, or manipulation constructs passed through the germline and targeted to gene loci for brain cell type-specific expression that are produced in a manner that very substantially reduces the time, cost, and breeding required by current methods in experimental vertebrate organisms.
• Combinations of molecular access reagents that intersectionally refine expression or delivery of monitoring and manipulation constructs to brain cell types with greater specificity.
• Collection of systemically administered viral or non-viral reagents that efficiently cross the blood brain barrier and direct construct expression to molecularly defined brain cell types and that detarget peripheral organs.
• Viral or non-viral vectors that enable neuronal projection mapping of or transsynaptic tracing initiated from defined brain cell types.
• RNA-based reagents to target brain cell types based on nucleic acid complementarity, protein-RNA interaction, or other interactions.

3. Disseminating Armamentarium RRDD Reagents to Neuroscience Researchers:

• Widespread dissemination of cell type access and manipulation reagents for brains of vertebrate animals and/or human ex vivo brain tissue or cells to identify, characterize, and/or alter potentially disease-relevant neural cells or circuits.
• Creation and maintenance of website-based catalogues of produced access reagents for users, showing inventory levels, efficacy, reproducibility, stability, activity, and unique characteristics of reagents; providing data on ongoing demand; and enabling receipt and incorporation of constructive user feedback on reagent performance, quality, quantity, timeliness, ordering processes, delivery, cost, feature requests, and related issues.
• Broad distribution of reagent use protocols that define parameters and methods for brain cell type-selective reagent use administered systemically or intracranially to minimize undesirable, perturbative effects of vectors or payloads.
• Large-scale brain cell type-selective reagent manufacturing and dissemination platforms that ensure quality control, quality assurance, and adequate supply for neuroscience community users, including assessment of the quality of reagents.
• Integration of data on reagent performance, improvement of reagents, and provision of feedback to reagent designers.
• Organization of reagent inventories and management of domestic and international deliveries to users.

4. Armamentarium Reagent Data Coordination:

• Tracking RRDD project reagent data and metadata deposition at BRAIN Initiative data archives.
• Creating website links for reagents in PDF catalogues, where neuroscience research users can order reagents, to the additional reagent data catalogued at the RRDD projects.
• Creating website links in PDF reagent catalogues to reagent data at BRAIN Initiative data archives.
• Organizing in-person and/or videoconference meetings that include the Armamentarium Steering Group meetings to facilitate communication within the consortium about reagent data.

Non-responsive Areas of Research

The following research areas are considered outside the scope of this NOFO, and such applications will be considered non-responsive and will not be reviewed:

• Applications that fail to propose to address all four main functions of a PDF: (1) interfacing with one or more RRDDs, (2) scaled-up RRDD validation reagent production, (3) disseminating reagents, and (4) Armamentarium reagent data coordination.
• Applications that fail to include proposed milestones and a proposed timeline.
• Applications primarily focused on the pursuit of a biological mechanism or a hypothesis through basic research that does not result in the generation of a scaled-up reagent production and distribution facility.
• Studies primarily focused on technology development that do not propose a scalable reagent resource. Note: Applications for technology development may be submitted to a separate BRAIN Initiative NOFO (including RFA-MH-24-280, RFA-MH-23-295, or reissues).

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 - Including the NIH Intramural Program
• 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) are not eligible to apply.

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. 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.

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

2. Cost Sharing

This 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 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:
Email: nimhpeerreview@mail.nih.gov

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 SF424 (R&R) Application Guide must be followed.

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

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

In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section. The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review. Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups historically  under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp.

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

Applicants may include project management personnel for the proposed facilities for the production and distribution of reagents as Senior/Key Person(s).

R&R Budget

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

PEDP implementation costs:

• Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm).

Include the following costs in each annual budget:

• Costs for product development, characterization, and testing to maintain a minimal inventory of reagents. Costs should include the purification, formulation, vialing, characterization, evaluation, quality control, quality assurance and/or other related activities.
• Costs for project management and website/catalogue development and maintenance.
• Costs for attendance at the anticipated annual in-person meeting for the research consortium.

Do not include in the budget:

• Production costs to manufacture reagents beyond the minimal inventory for distribution. Neuroscience research users requesting reagents are required to pay for production costs.
• Shipment and delivery of reagents. Neuroscience research users requesting reagents are required to pay for shipping costs.

R&R Subaward Budget

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

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

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

Research Strategy

1. Throughout the Research Strategy, applicants must address a Production and Distribution Facility plan as outlined below.

Significance: For each Specific Aim individually or for all Specific Aims collectively, explain the following:

• How the project will align with the overarching goal of the BRAIN Initiative Armamentarium project to generate molecular or genetic reagents to specifically access brain cell types in the study of circuit function for several vertebrate species, including human ex vivo tissue or cells.
• Importance of the reagents to be produced and distributed.
• Need for the scale up of reagent dissemination.

Innovation: For each Specific Aim individually or for all Specific Aims collectively, explain the following:

• Innovations in the scaling up of reagent production, quality control/assurance, characterization of properties, inventory management, and/or distribution strategies.
• New strategies in cataloguing of reagent inventory and/or bidirectional facility/user communication.
• Novel approaches in the data coordination efforts in ensuring distribution of reagent data.

1. Interface plans with the Armamentarium RRDD projects.  Provide details on:

• Receiving validated seed reagents, reagent templates, and/or reagent designs from one or more Armamentarium RRDD projects that were made under RFA-MH-25-100.  (The RRDD projects will design, validate, catalogue, and adapt into easily disseminable formats brain cell type-selective reagents to be distributed by the PDFs.)
• Working with RRDD projects to improve the reagents, optimize the scaling up of reagent production, and/or further catalogue the reagents at the PDF.

2. Scaled-up reagent production plans.  Provide details on:

• Scaling up reagent production at the PDF of the validated reagents received from RRDD projects.
• Controlling the quality of reagents and assuring the quality of production processes.
• Characterizing, formulating, evaluating, and validating the efficacy, reproducibility, stability, activity, and unique characteristics of produced reagents.
• Highly purifying and producing reagents in a manner safe and appropriate for use in animals and/or human ex vivo tissue and cells.
• Storing reagents, managing inventory, and distributing reagents domestically and internationally.

3. Reagent dissemination plans.  Provide details on:

• Cataloguing scaled-up product inventory for dissemination to users for neuroscience research. Such catalogues should be planned to be made widely accessible and kept updated.
• Managing reagent delivery to users.
• Assessing the ongoing user demand for various reagents as well as receiving and incorporating constructive user feedback. Plans for feedback should include consideration of the reactions from the user community in terms of reagent performance, quality, quantity, timeliness, ordering processes, delivery, cost, feature requests, and related issues..
• Maintaining a website to achieve the above user interface objectives.
• Managing and overseeing large-scale production and distribution activities including, but not limited to, material transfer and licensing agreements, webhosting, and recovery of production and distribution costs.
• Conducting project management at the proposed PDF for the production and dissemination of reagents.

4. Data coordination plans.  Provide details on:

• Ensuring that all RRDD project data and metadata for reagent engineering and validation are deposited in a timely manner at data archives according to the BRAIN Initiative Data Sharing Policy.
• Ensuring that accessible interfaces are maintained to link the PDF reagent catalogues, where neuroscience research users can order reagents, to the additional reagent data catalogued at the RRDD projects.
• Ensuring that accessible interfaces are maintained to link the PDF reagent catalogues to RRDD data deposited at data archives in accordance with the BRAIN Initiative Data Sharing Policy.
• Organizing meetings that include the Armamentarium Steering Committee meetings to facilitate communication within the consortium about reagent data. This plan for organizing meetings that include the Armamentarium Steering Committee should be provided as a separately labeled subaim.

Proposed Milestones and Timeline

Applications must include Proposed Milestones and Timeline. The Proposed Milestones and Timeline should explain critical indicators of progress for the interfacing with RRDD projects, scaled-up reagent production, reagent dissemination, and reagent data coordination.

Letters of Support

Letters of support from potential facility users are encouraged. In the letters, users should describe their research plans with a level of detail sufficient for reviewers to assess the potential impact of the proposed facility. No more than 5 letters from potential end users may be submitted. It is encouraged that these letters demonstrate the applicant has considered diverse perspectives from the end user community. Applications may also include institutional letters which describe financial and collaborative arrangements, and/or agreements for payment for services, or letters which describe third party or strategic partner interest. The Letters of Support attachment of the application should include a cover page listing the name, institution, and proposed role for each individual providing a letter of support.

Program Income

Applicants should describe plans for Program Income, if any, including the expected charges to the neuroscience research community for distributing reagents.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. 

The following modifications also apply:

A central goal of this NOFO is to produce and distribute transformative tools that will be widely used throughout the research community. Applications are expected to include a detailed plan for sharing these resources and expected to include the following key elements:

• Project management of resource sharing;
• Description of what specific resources will be shared (e.g., model organisms, reagents, etc.);
• Schedule/timeline for availability of resources to other users;
• Persons who will have access to the resources (written as broadly as possible to the extent consistent with applicable laws, regulations, rules, and policies);
• Plan for post award disposition of resources.
• Investigators are strongly encouraged to obtain a research resource ID from the Resource Identification Initiative (https://scicrunch.org/resources/about/resource) and to use Resource IDs in publications if available. (https://scicrunch.org/resources).
   

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 SF424 (R&R) 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.
• The data sharing expectations for BRAIN Initiative awards require that the data is deposited to relevant data archives developed by the BRAIN Initiative. Applicants can refer to NOT-MH-19-010, for more information about BRAIN Initiative data sharing information.

To advance the goal of advancing research through widespread data sharing among researchers, investigators funded under this Notice of Funding Opportunity (NOFO) are expected to share those data via the National Institute of Mental Health Data Archive (NDA; see NOT-MH-23-100). Established by the NIH, NDA is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research data, tools, and supporting documentation. NDA links data across research projects through its Global Unique Identifier (GUID) and Data Dictionary technology. Investigators funded under this NOFO are expected to use these technologies to submit data to NDA.

To accomplish this objective, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to generate a GUID for each participant, and b) a budget strategy that will cover the costs of data submission. The NDA website provides two tools to help investigators develop appropriate strategies: 1) the NDA Data Submission Cost Model which offers a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal Investigator and Data Manager to budget for data sharing; and 2) plain language text to be considered in your informed consent available from the NDA's Data Contribution page. Investigators are expected to certify the quality of all data generated by grants funded under this NOFO prior to submission to NDA and review their data for accuracy after submission. Submission of descriptive/raw data is expected semi-annually (every January 15 and July 15); submission of all other data is expected at the time of publication, or prior to the end of the grant, whichever occurs first (see NDA Sharing Regimen for more information); Investigators are expected to share results, positive and negative, specific to the cohorts and outcome measures studied. For more guidance on submitting data to NDA, refer to the NDA Data Sharing Plan on the NDA website. NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary.

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

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

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 SF424 (R&R) Application Guide.  Paper applications will not be accepted.

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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 SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. 

Applications must include annual milestones. Applications that fail to include annual milestones will be considered incomplete and will be withdrawn.  Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn before review. 

Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at nimhreferral@mail.nih.gov when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

Applications Involving the NIH Intramural Research Program

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as co-investigators in accord with the Terms and Conditions provided in this Notice of Funding Opportunity (NOFO). Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

 Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

NIMH expects investigators for this funding announcement to collect Common Data Elements (CDEs) for mental health human subjects research. Unless NIMH stipulates otherwise during the negotiation of the terms and conditions of a grant award, this Notice applies to all grant applications involving human research participants. The necessary funds for collecting and submitting these CDE data from all research participants to the NIMH Data Archive (NDA) should be included in the requested budget. A cost estimator (https://nda.nih.gov/ndarpublicweb/Documents/NDA_Data_Submission_Costs.xlsx) is available to facilitate the calculation of these costs. NIMH may seek further information regarding CDEs prior to award. Additional information about CDEs can be found at the NIMH webpage on Data Sharing for Applicants and Awardees.

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:

• This NOFO specifically seeks applications to scale up the production and distribution of brain cell type-selective reagents in several vertebrate species, including human ex vivo tissue and cells.  The NIH expects that some applications may propose mature and well-established approaches that may not be innovative per se to produce and distribute robust high-quality reagents for broad use by neuroscience researchers. In addition, this NOFO seeks applications for Production and Distribution Facilities (PDFs) for reagents specifically emanating from Research Resource for Design and Development (RRDD) projects that are separately supported by the BRAIN Initiative Armamentarium project.

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 projects 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 projects?

Specific to this NOFO:

• How likely is the planned reagent production and distribution facility project to be significant for disseminating brain cell type-selective access reagents to neuroscience researchers? 
• From details provided in the letters of support, how much value will the facility add over any comparable facilities? 
• How relevant is the proposed scale of reagent dissemination?  
• How useful are the planned user interfaces for reagent distribution?  
• How valuable are the proposed data coordination efforts for the facility to ensure distribution of reagent data to data archives, reagent users, and consortium researchers? 
• To what extent do the efforts described in the Plan for Enhancing Diverse Perspectives further the significance of the project?

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 cell type-selective reagent research? Do the investigators demonstrate significant experience with coordinating collaborative basic 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:

• To what extent have the investigators, collaborators, or other researchers demonstrated experience and expertise in scalable production and dissemination of reagent resources? 
• To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives strengthen and enhance the expertise required for the project?

Innovation

Does the application propose novel organizational concepts, management strategies, or methods in coordinating the research projects 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 organizational concepts, management strategies or methods proposed?

 Specific to this NOFO:

• How well does the application integrate existing approaches in novel ways? 
• How cutting-edge are the methods for scaling up of reagent production, quality control/assurance, characterization of properties, inventory management, and/or distribution? 
• To what extent are the cataloguing of reagent inventory and/or receiving user feedback new?  
• How novel are the plans for data coordination efforts to ensure distribution of reagent data?  
• To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives meaningfully contribute to innovation?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research projects the Resource will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the projects, 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 appropriate are the plans to interface with the Armamentarium RRDD project investigators (recipients of RFA-MH-25-100), who will design, validate, catalogue, and adapt into easily disseminable formats brain cell type-selective reagents?
• How feasible are the plans to conduct scaled-up production of the designed and validated reagents?
• How effective will the proposed facility be in disseminating reagents to neuroscience research users?
• How well reasoned are plans to coordinate the distribution of reagent data to data archives, reagent users, and consortium researchers?
• Are the timeline and milestones associated with the Plan for Enhancing Diverse Perspectives well-developed and feasible?

Environment

Will the institutional environment in which the Resource will operate contribute to the probability of success in facilitating the research projects 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?

Specific to this NOFO:

• To what extent will the environment enable scalable production and dissemination of reagent resources? 
• To what extent will features of the environment described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support) contribute to the success of the project?

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.

Milestones and Timeline

• To what extent are the Proposed Milestones and Timeline described in sufficient detail and are they appropriate for the project? How reasonable is the timeline? How feasible, well-developed, and quantifiable are the milestones with regard to the specific aims?

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

Not Applicable

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

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the 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 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 NIMH, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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

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 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 National Advisory Mental Health Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities including the PEDP.

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

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

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

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, 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.

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 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.

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

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 responsibilities as described below:

• Scale up production and distribution of brain cell type-selective access reagents for the neuroscience field.
• Determine and coordinate the research approaches and procedures, conduct experiments, and analyze and interpret research data generated under this award.
• Meet or exceed the timeline stated in their application.
• Agree to participate as a voting member in a Consortium Steering Group composed of other recipients from this NOFO and RFA-MH-20-556, RFA-MH-21-180, RFA-MH-22-245, RFA-MH-25-100, NIH staff, and an external expert group.
• Share protocols, technologies, reagents, and data with consortium members.
• Not disclose confidential information obtained from other consortium members.
• Ensure that results are published in a timely manner.
• Coordinate with other consortium members the publication of research results, dissemination of reagents, and dissemination of data.
• Submit protocols, reagents, and data for use, quality assessment, and/or validation in any manner specified by the Steering Group or the NIH Project Scientist.
• Submit annual milestone reports to the NIH with completeness that include experimental design with rigor, including assumptions for the design of the experiments, the results of the investigations, interpretations of the results, and for concluding whether milestones have been met or not.
• Provide updates at least annually on implementation of the PEDP.
• Accept and implement common guidelines and procedures approved by the Steering Group.
• Attend Steering Group meetings. It is likely that there will be one in-person meeting per year and that other meetings will be held by telephone or using internet-assisted meeting software.

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

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

• A Program Officer will be assigned to this award. The Program Officer will be responsible for normal scientific and programmatic stewardship and guidance and will be named in the notice of award.
• Prior to award, the Program Officer will negotiate final milestones with the PD/PIs that will be incorporated into the Notice of Award.
• A group of NIH program staff from the ICs that make up the NIH BRAIN Initiative will form a Project Team for this award.
• The Project Team will include the Program Officer for these BRAIN Initiative awards.
• The Project Team will review annual progress reports and other documents from the recipients and will advise the Program Officer about their view of the progress being made by the recipient as well as about progress being made by others in the field.
• One or more extramural NIH program staff member will be assigned as Project Scientist for this award. The same person may serve as a Project Scientist for multiple BRAIN Initiative awards.
• The Project Scientist(s) will interact scientifically with the PDs/PIs of the cooperative agreement and other named key personnel as a partner in the research activities.The  Project Scientist(s) will be members of the Steering Group.

Areas of Joint Responsibility include:

• The purpose of the Steering Group is to transfer information and technologies among the recipients of this NOFO, RFA-MH-20-556, RFA-MH-21-180, RFA-MH-22-245, and RFA-MH-25-100 and between the recipient and the BRAIN Initiative more broadly in order to achieve the goals outlined in the BRAIN 2025 and BRAIN 2.0 reports.
• The Steering Group will be comprised of the PDs/PIs of the awards of this NOFO, RFA-MH-20-556, RFA-MH-21-180, RFA-MH-22-245, RFA-MH-25-100, the Project Scientist(s),  and a group of external experts.
• The PDs/PIs and Program Officer will invite a group of external experts to attend Steering Group meetings. The external expert group will be composed of three to five scientists who are not recipients of this NOFO, RFA-MH-20-556, RFA-MH-21-180, RFA-MH-22-245, RFA-MH-25-100, represent the broad research community, and have relevant expertise. The group may be enlarged permanently or on an ad hoc basis as needed.
• A chair of the Steering Group, who is a recipient of this NOFO, RFA-MH-20-556, RFA-MH-21-180, RFA-MH-22-245, RFA-MH-25-100, will be designated by the Steering Group on a rotating basis as needed.
• It is expected that most of the decisions on the activities of the Steering Group will be reached by consensus. If a vote is needed, each award will have one vote and the Project Scientist(s) collectively will have one vote. When a vote is required, at least 60% of the votes will be required for approval.
• The Project Scientist may assist in research planning, may present experimental findings from an award from published sources or from relevant award projects, may participate in the design of experiments agreed to by the group, may participate in the analysis of results, may help ensure that duplication is avoided, and will interact scientifically with the Steering Group.
• The Program Officer and the external expert group members will attend Steering Group meetings as non-voting  observers.
• In all cases, the role of NIH staff will be to assist and facilitate, but not to direct activities.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee for the investigators chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of disagreement, 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 DHHS regulation 45 CFR Part 16. Final decisions made by NIH regarding a discontinuation are not appealable.

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.

Recipients will provide updates at least annually on implementation of the PEDP.

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. 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.

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

In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 2 CFR Part 200 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

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: GrantsInfo@nih.gov (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: support@grants.gov

Douglas S. Kim, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-6463
Email:douglas.kim@nih.gov

Nicholas Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: nick.gaiano@nih.gov

Heather Weiss
National Institute of Mental Health (NIMH)
Telephone: 301-443-4415
Email: weissh@mail.nih.gov 

Section VIII. Other Information

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

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.