NIH BRAIN Initiative: Development and Validation of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in the Brain (R01)

NIH BRAIN Initiative: Development and Validation of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in the Brain (R01) is sponsored by National Institutes of Health (NIH). Encourages applications to develop and validate novel tools for detailed analysis of complex neural circuits and cellular interactions.

Expired RFA-MH-21-175: BRAIN Initiative: Development and Validation of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in the Brain (R01 Clinical Trial Not Allowed) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Mental Health ( NIMH ) National Eye Institute ( NEI ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) National Institute of Biomedical Imaging and Bioengineering ( NIBIB ) Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute on Deafness and Other Communication Disorders ( NIDCD ) National Institute on Drug Abuse ( NIDA ) National Institute of Neurological Disorders and National Center for Complementary and Integrative Health ( NCCIH ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.

The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Behavioral and Social Sciences Research ( OBSSR ) Funding Opportunity Title BRAIN Initiative: Development and Validation of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in the Brain (R01 Clinical Trial Not Allowed) R01 Research Project Grant February 8, 2023 - Notice of Intent to Publish a Funding Opportunity Announcement for BRAIN Initiative: Optimization of Instrumentation and Device Technologies for Recording and Modulation in the Nervous System (U01 Clinical Trials Not Allowed).

See Notice NOT-NS-23-036 February 8, 2023 - Notice of Intent to Publish a Funding Opportunity Announcement for BRAIN Initiative: New Technologies and Novel Approaches for Recording and Modulation in the Nervous System (R01 Clinical Trial Not Allowed).

See Notice NOT-NS-23-035 NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022 October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available.

See Notice NOT-OD-22-018 . September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022.

August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170 April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel.

See Notice NOT-OD-21-109 September 21, 2021 Notice of Change to Key Dates of RFA-MH-21-175, "BRAIN Initiative: Development and Validation of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in the Brain (R01 Clinical Trial Not Allowed)". See Notce NOT-MH-21-345 Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) 93. 242, 93.

279, 93. 865, 93. 867, 93.

866, 93. 213, 93. 273, 93.

173, 93. 853, 93. 286 Funding Opportunity Purpose The purpose of this Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is to encourage research that will develop and validate novel tools to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function.

The new tools and technologies should inform and/or exploit cell-type and/or circuit-level specificity. Plans for validating the utility of the tool/technology will be an essential feature of a successful application.

The development of new genetic and non-genetic tools for delivering genes, proteins and chemicals to cells of interest or approaches that are expected to target specific cell types and/or circuits in the nervous system with greater precision and sensitivity than currently established methods are encouraged. Tools that can be used in a number of species/model organisms rather than those restricted to a single species are highly desired.

Applications that provide approaches that break through existing technical barriers to substantially improve current capabilities are highly encouraged. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to the application due dates Renewal / Resubmission / Revision (as allowed) All applications are due by 5:00 PM local time of applicant organization.

All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s). 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.

New Date May 8, 2023 per issuance of RFA-MH-23-290 Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide ,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description 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. 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 FOAs .

The BRAIN Initiative requires a high level of coordination and sharing between investigators. It is expected that BRAIN Initiative awardees 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 FOA is related to the Recommendations in Section III. 1 and 2 of the " BRAIN 2025: A Scientific Vision " report of the BRAIN Multi-Council Working Group . Specifically, this FOA solicits applications that address the report recommendations on "Discovering Diversity" and "Maps at Multiple Scales", (Section III).

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 major achievements made along the way, many specific details about the brain remain to be discovered, 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. Improved technology is needed to obtain this knowledge.

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 ongoing to study large-scale, long-range connections, such as the NIH Human Connectome Project .

Recent development of new technologies (e.g., hydrogel-based brain tissue clearing, expansion microscopy, spatial transcriptomics, and several other imaging breakthroughs) allows an unprecedented three-dimensional view into the post-mortem brain. 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.

An emphasis of the BRAIN initiative is the development of novel tools to study the brain, and 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 requires a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application (see further below).

Applicants are strongly encouraged to read the FOA instructions carefully and view the available PEDP guidance material . Applications must include a Plan for Enhancing Diverse Perspectives (PEDP) submitted as Other Project Information as an attachment (see Section IV).

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. Responsive Areas of Research 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 electron- and light-microscopy level. Innovative approaches to reduce the time and cost of determining high resolution synaptic connectivity by electron microscopy or other approaches.

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 gene profiling using FISH and sequencing methodologies. Novel methods for visualizing or manipulating epigenomic marks or gene expression 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.

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. Novel technologies to target and characterize non-neuronal cells, including glial and vascular cells, in the brain.

Non-responsive Areas of Research The following research areas are considered outside the research scope of this FOA, and such applications will be considered non-responsive and will not be reviewed: Studies primarily focused on the pursuit of a biological mechanism or a hypothesis.

Applicants are strongly encouraged to consult the NIMH Scientific/Research Contact, listed below, to discuss the alignment of their proposed work with Development and Validation of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in the Brain (R01) and BRAIN Initiative program goals. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Only those application types listed here are allowed for this FOA. Not Allowed: Only accepting applications that do not propose clinical trials. Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards Issuing IC and partner components intend to commit an estimated total of $8 million to fund 6-9 awards. Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period.

The maximum project period is 3 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA. Section III.

Eligibility Information 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 (Other than Small Businesses) 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 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 Non-domestic (non-U.S.) Entities (Foreign Institutions) 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. 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. 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) 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.

gov registration, but 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 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.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement. 3. Additional Information on Eligibility 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 ) 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 FOA. 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 SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. 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: 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. 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 with the following additional instructions:. Plan for Enhancing Diverse Perspectives (PEDP) 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 traditionally 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 . SF424(R&R) Senior/Key Person Profile 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: 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 ). 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.

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. Applicants are expected to address if proposed tool(s) have the potential to be applied in multiple model species. The tools should enable analysis of brain circuitry underlying complex behaviors.

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. The following modifications also apply: 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 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, 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 ). Data Sharing Plan : All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan as part of