Department of Health and Human Services

Part 1. Overview Information

Key Dates

Required Application Instructions

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

Table of Contents

1. Part 1. Overview Information
2. Part 2. Full Text of the Announcement
   1. Section I. Funding Opportunity Description
   2. Section II. Award Information
   3. Section III. Eligibility Information
   4. Section IV. Application and Submission Information
   5. Section V. Application Review Information
   6. Section VI. Award Administration Information
   7. Section VII. Agency Contacts
   8. Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative is a Presidential project aimed at revolutionizing our understanding of the human brain. By accelerating the development and application of innovative technologies, researchers will be able to produce a new dynamic picture of the brain that, for the first time, shows how individual cells and complex neural circuits interact in both time and space. It is expected that the application of these new tools and technologies will ultimately lead to new ways to treat, cure, and even prevent brain disorders.

NIH is one of several federal agencies involved in the BRAIN Initiative. Planning for the NIH component of the BRAIN initiative is guided by the long-term scientific plan, BRAIN 2025: A Scientific Vision, which details seven high-priority research areas and calls for a sustained federal commitment of $4.5 billion over 12 years. This report can be found at http://braininitiative.nih.gov/ . This FOA and other FOAs issued in Fiscal Year 2015 are based on careful consideration by the NIH of the recommendations of the BRAIN 2025 Report, and input from the NIH BRAIN Multi-Council Working Group (http://braininitiative.nih.gov/MCWG-Roster.pdf ), which held its first meeting on August 25th, 2014 (see http://videocast.nih.gov/summary.asp?file=18555&bhcp=1 ).

In addition to the National BRAIN initiative, the NIH continues to have a substantial annual investment in neuroscience research. The Institutes and Centers contributing to the NIH BRAIN Initiative (http://braininitiative.nih.gov/ ) support those research efforts through applications received via parent announcements as well as through specific funding opportunity announcements. Potential applicants to this FOA are strongly encouraged to contact Scientific/Research staff if they have any questions about the best funding opportunity announcement for their research.

To enable progress in development of new technologies as well as in theory and data analysis, the BRAIN Initiative encourages collaborations between neurobiologists and scientists from statistics, physics, mathematics, engineering, and computer science, and NIH welcomes applications from investigators in these disciplines.

NIH encourages BRAIN Initiative applications from groups that are underrepresented in the biomedical, behavioral, or clinical research workforce (see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27 and the most recent report on Women, Minorities, and Persons with Disabilities in Science and Engineering ). Such individuals include those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds.

The BRAIN Initiative will require a high level of coordination and sharing between investigators, and this FOA will use a cooperative agreement to facilitate these activities. The details of the management of the cooperative agreements can be found in Section VI. It is expected that BRAIN Initiative awardees will cooperate and coordinate their activities after awards are made.

This FOA is related to the Recommendations in Section III.1 and 2 of the Final Report (http://www.nih.gov/science/brain/2025/index.htm ) of the BRAIN working group. Specifically, this FOA solicits applications that will address the recommendations on "Discovering Diversity" and "Maps at Multiple Scales", (Section III).

Research Objectives

This funding opportunity announcement (FOA) is designed to support development and validation of novel tools to facilitate the detailed analysis of cells and circuits and provide insights into the neural circuitry and structure underlying complex behaviors. The human brain consists of an estimated one hundred billion neurons and more than one trillion supporting glial cells that are uniquely organized to confer the extraordinary computational activities of the brain. Cell types are categorized by their anatomical position, neurotransmitter content, dendritic and axonal connections, receptor profile, gene expression profile and distinct electrical properties. Although the human brain has long been the focus of numerous studies with many major achievements along the way, to date we remain largely ignorant about the specific details such as cell types and connections that are responsible for rapid information processing. Defining cellular and circuit-level function is dependent on detailed knowledge about the components and structure of the circuit. Such knowledge, in turn, is fundamental to understanding how these features underlie cognition and behavior, which should aid in the development of targeted cell-type and circuit-specific therapeutics to treat brain disorders. This initiative is focused on developing tools (or vastly improving existing tools) to enable access to individual cells and defined groups of cells within neuronal circuits. The tools sought through this FOA can include novel genetic or non-genetic methods for targeted delivery of genes, proteins, and chemicals to specific cells or tightly defined cell types and circuits.

Development of novel tools that will delineate anatomical connections between cells and expand our knowledge of circuit architecture and function is an area well poised for additional investment. Several efforts are currently underway to study large-scale, long-range connections, such as the NIH Human Connectome Project, as well as large scale rodent connectional studies. Recent development of new technologies (e.g., CLARITY, Lumos) that render the brain essentially transparent while maintaining the integrity of cellular and subcellular components, allow an unprecedented three-dimensional view into the post-mortem brain. While still at an early stage, these exciting technologies hold promise for mapping short- and long-range connections throughout the brain. Coupled with improved activity monitoring technologies in awake, behaving animals, these new tools promise an understanding of circuitry in action. Further development of these technologies is crucial to push the envelope beyond our current capabilities. To this end, applicants from the biological sciences are encouraged to establish collaborations with nanobiologists, material scientists, engineers and colleagues in other disciplines to develop groundbreaking approaches to study brain activity.

This FOA solicits applications to develop next-generation, innovative technologies to define and target specific cell types in the brain. Of particular interest are first-in-class and/or cross-cutting non-invasive or minimally invasive techniques that permit repeated measurements from cells over time in a non-destructive manner. Tools/technologies relevant for this initiative are expected to be transformative, either through the development of novel tools that may be high-risk or through major advances in current approaches that break through technical barriers and will significantly improve current capabilities. While an emphasis of the BRAIN initiative is the development of novel tools to study the brain, here we highlight the need for innovative approaches to bridge experimental scales. Studies that are able to explore molecular and cellular mechanisms of neural activity permitting improved precision and sensitivity in the analysis of micro-and macro-circuits are strongly encouraged. Progress in understanding how the activity of the brain translates to complex behaviors will be facilitated by non-invasive approaches for both monitoring and manipulating neural activity in awake, behaving organisms.

This FOA seeks applications in areas including, but not limited to:

• Novel methods (non-genetic and genetic) to deliver active agents to specific neurons in particular neural circuits or brain areas with no or minimal cytotoxic effects.
• Novel methods for tagging individual neurons such that cellular components of a functional circuit can be explored.
• Novel trans-synaptic tracers that can be used both at the EM and light-microscopic level.
• Significantly improved viral-mediated gene delivery that targets specific cells or cell types in the nervous system.
• Innovative ways to use multiple vectors to deliver split gene products to limit and/or control expression in specific cell types.
• Novel, transgenic methods in multiple model species to allow more refined cell-specific and circuit-specific manipulation.
• Chemical or genetic engineering of blood brain barrier-crossing carrier agents (such as tagged antibodies or other tools) to allow delivery of specific cargoes (e.g., neuronal activity, effectors, tracers or sensors) to specific cells or circuits.
• Novel methods for non-invasive, targeted access to, or manipulation of, distinct cell types in defined circuits with spatio-temporal control.
• Novel trans-synaptic tracers that can work in retrograde and anterograde direction, or deliver cargoes to cells in the nervous system.
• Enhanced temporal and spatial resolution techniques for noninvasive molecular imaging of neuronal cells for in situ brain studies.
• Unique combinations of tools for multiplex analysis and/or manipulation of single cells in situ to maximize data content over many parameters (e.g., RNAs, proteins, metabolites, organelles, electrochemical dynamics, signal secretion/reception/transduction, cytoarchitecture or migratory changes).
• Innovative tools that provide significant advances in sensitivity, selectivity or spatiotemporal resolution of molecules/structures/activities within single cells in the brain and between ostensibly similar cells in situ (e.g., high resolution imaging of molecular interactions within single cells).
• Novel automated and scalable assays for high-throughput analysis of single cells in situ in the brain, including scalability of measured parameters in parallel, cell numbers and/or speed of processing.
• Unique systems-level single cell computational approaches to help define functional cell types and circuitry.
• New tools and approaches that minimize tissue and cell perturbations so that cell viability is maintained allowing for multiple repeated measures in the same cell over time.
• Development of in situ sequencing using FISH and other sequencing methodologies
• Novel methods for visualizing epigenomic marks in neural cells
• Novel computational approaches to analyze and integrate multi-scale datasets to better understand brain function.
• Innovative approaches to bridge scales of experimental approach. Studies that are able to explore molecular and cellular mechanisms of neural activity in broader contexts are encouraged.
• Innovative approaches to reduce the time and cost of determining high resolution synaptic connectivity by electron microscopy or other approaches.
• Novel techniques for integrating micro-scale connectivity data (e.g., by electron microscopy) with cellular or synaptic phenotypic information.
• Innovative molecular complementation methods to identify synaptic connections and determine their phenotypes.
• Novel uses of super-resolution light microscopic approaches for identifying synaptic connections and mapping micro-circuits.
• Development of cell type-specific molecular sensors and additional tools and approaches to address circuit-specific manipulation and monitoring.

Applicants are strongly encouraged to consult the appropriate Scientific/Research Contact , listed below, to discuss the alignment of their proposed work with Development and Validation of Novel Tools to Analyze Cell-Specific and Circuit-Specific Processes in the Brain (U01) and BRAIN Initiative Program goals.

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government - 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 Institutions)

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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.

Required Registrations

Applicant Organizations

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

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

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

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:

Michelle Freund, Ph.D.
National Institute of Mental Health
Telephone: 301-443-1815
Email: [email protected]

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed. Applicants should include sufficient funds to support travel to NIH for an annual BRAIN PD/PI meeting.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy: All applications should include the following:

Current State-of-the-Art Statement: Investigators should specifically define the current state of technology as a benchmark against which their proposed new technology or improvements will be measured. Preliminary/feasibility data are not required or expected for early-stage, high-risk projects. However, a sound rationale should be provided as to why the approach proposed is the most appropriate and likely to generate an exceptionally high impact if successful. In these cases, more emphasis should also be placed in details of the approach, particularly feasibility-testing. Applicants are expected to explain the specific biological assay(s) to be utilized in the application to validate the new tool in proof-of-concept testing.

Timeline: A timeline should be included as part of the Research Strategy and should include a distinct final section, entitled Milestones , that briefly proposes indicators of progress at critical junctures. These should be tailored to the unique scope of each project and written concretely enough to evaluate what exactly will have been achieved (e.g., crucial steps in tool making) during the course of the project. Given that projects are likely to be early stage and high-risk in nature, this should include the specific proof-of-concept test(s) that will indicate whether/how a proposed tool actually works , along with alternative strategies should that effort fail to perform as expected. Tests should include a comparison against existing benchmark technologies; if a tool is truly first-in-class, comparisons may be done against a nearest neighbor technology. Investigators should briefly note how results will be used to inform future phases of tool development such as testing in other model systems or in human brain.

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

• All applications submitted for the January 25, 2015 due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.

While it is understood that many tools will be at an early proof-of-concept stage, a central goal of this FOA is to generate transformative tools that will be widely used throughout the research community. Applications that propose to generate such tools are expected to include a detailed plan for sharing these resources and include the following key elements:

• Project management of resource sharing;
• Description of what specific resources will be shared (e.g., model organisms, reagents, completed tools or repurposed components);
• 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 (http://scicrunch.com/resources/info/add) and to use Resource IDs in their publications if available. (http://scicrunch.com/resources ).

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

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

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

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

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

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

6. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

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

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

See more tips for avoiding common errors.

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

In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at [email protected] when the application has been submitted. Please include the FOA 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 PDs/PIs in accord with the Terms and Conditions provided in this FOA. 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.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Overall Impact

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the tool or technology confer a high degree of cell or circuit-specificity? Has the state of the art been accurately described? Does the tool have the potential to be applied in multiple species or model organisms? Will the proposed study be significant to developing and validating novel tools to analyze cell-specific and circuit-specific processes in the brain?

Investigator(s)

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

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Does the proposed work address existing barriers? Will the proposed tool enable discovery related to brain circuitry underlying complex behaviors? Are the proposed tools/technologies potentially transformative either through the development of novel tools that may be high-risk or through major advances in current approaches that break through technical barriers and will significantly improve current capabilities?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Are the appropriate studies included to validate the technology? Is a sound rationale provided as to why the approach proposed is the most appropriate and is likely to generate an exceptionally high impact if successful?

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 children, justified in terms of the scientific goals and research strategy proposed?

Environment

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

Additional Review Criteria

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

Milestones and Timelines

Are the Proposed Milestones and Timeline described in sufficient detail and are they appropriate for the project? Is the timeline reasonable? Are the milestones feasible, well developed, and quantifiable with regard to the specific aims?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

When the proposed project involves 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 children 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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

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 following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

While it is understood that many tools will be at an early proof-of-concept stage, a central goal of this FOA is to generate transformative tools that will be widely used throughout the research community. For applications that propose to generate such tools, does the application include an adequate and detailed plan for sharing these resources? Does the plan provide a strong rationale for each of the following key elements?

• Project management of resource sharing;
• Description of what specific resources will be shared (e.g., model organisms, reagents, completed tools or repurposed components);
• 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.

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:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

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

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

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.

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

Any application awarded in response to this FOA will be subject to 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.

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

• PD(s)/PI(s) will determine and coordinate the research approaches and procedures, conduct experiments, and analyze and interpret research data generated under this award.
• PD(s)/PI(s) will endeavor to meet or exceed the timeline stated in their application.
• PD(s)/PI(s) will agree to participate as a voting member in a Steering Group as described below under Areas of Joint Responsibility.
• PD(s)/PI(s) will share resources and data in a consistent manner and as developed by the Steering Group.
• PD(s)/PI(s) will ensure that results are published in a timely manner.
• PD(s)/PI(s) will submit data for quality assessment and/or validation in any manner specified by the Steering Group or the NIH Project Scientist.
• PD(s)/PI(s) will submit periodic progress reports as specified by the Notice of Grant Award.
• PD(s)/PI(s) will accept and implement any other common guidelines and procedures approved by the Steering Group.
• PD(s)/PI(s) will attend Steering Group meetings. It is likely that there will be one in-person meeting per year and that other meetings will be by telephone or using internet assisted meeting software.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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.
• An NIH Project Team composed of NIH Program Staff of the ensuing awards as well as other Program staff of the BRAIN ICs, will be created to ensure communication and continuity among the interested NIH ICs related to coordination among BRAIN Initiative awards and with other grant or contract activities by NIH.
• The Project Team will include and be led by the Program Officer(s) assigned to these BRAIN Initiative awards.
• One extramural NIH program staff member will be assigned as the Project Scientist for an award. The same person may serve as the Project Scientist for multiple BRAIN Initiative awards, or others may serve as Project Scientist
• The Project Scientist will also be a member of the Project Team.
• The Project Scientist for an award will interact scientifically with the PDs/PIs and other named personnel of that award, as a partner in the research.
• The Program Officer(s), the Project Scientist(s), and one member of the Project Team will be members of the Steering Group, as described below under Areas of Joint Responsibility.

Areas of Joint Responsibility include:

• A Steering Group is formed whose purpose is to transfer information between BRAIN Initiative awardees in order to achieve the goals outlined in the BRAIN Initiative Working Group Final Report.
• The Steering group is composed of PD/PIs, Project Scientist(s), the Program Officer(s) and one other member of the Project Team.
• 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 awardee will have one vote, and the Project Scientist(s) will each have a vote. The number of NIH votes will not exceed one-third of the total votes, since the expectation is that one or more Project Scientists will serve that role on more than one award. When a vote is required, at least 60% of the votes will be required for approval. The Program Officer and the other member of the Project Team will be non-voting participants.
• The Project Scientist interacts scientifically with the Steering Group and may assist in research planning, may present experimental findings to the Steering group from published sources or from relevant contract projects, may participate in the design of experiments agreed to by the Steering group, may participate in the analysis of results, and may help ensure that duplication is avoided.
• 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 of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: [email protected]

Scientific/Research Contact(s)

Michelle Freund, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-1815
Email: [email protected]

Peer Review Contact(s)

David Armstrong, Ph. D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3534
Email: [email protected]

Financial/Grants Management Contact(s)

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
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.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.