NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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 the 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

The tau protein belongs to a group of proteins referred to as Microtubule-Associated Proteins (MAPs). Tau plays a key role in regulating the cytoskeletal architecture in the neuron through its role in promoting the assembly and stabilization of microtubules. In 1998, the identification of exonic and intronic tau gene (MAPT) mutations associated with FTDP-17 established that tau dysfunction can cause neurodegeneration. Tauopathies captured under the syndrome defining FTD include Pick's disease, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17).

The mechanisms by which tau protein becomes a nonfunctional entity are unknown. Abnormal posttranslational modifications (hyper-phosphorylation, acetylation, glycation, ubiquitination, and nitration) are proposed to be key causes of this failure. However, other modifications like proteolytic cleavage (truncation), protein conformational changes, disease causing mutations, and splicing abnormalities have also been proposed to cause the loss of normal function and the gain of pathological features for the tau protein. Recently, the identification of potential oligomeric soluble tau toxic species and the ability of tau species to be transmitted from neuron to neuron, further complicate the potential mechanisms involved in neurotoxicity for FTD related tauopathies.

In 2013, NINDS organized a conference on Alzheimer's Disease Related Dementias (ADRDs) which focused on frontotemporal degeneration (FTD), Lewy body dementias (LBD) (including dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD)), vascular cognitive impairment or dementia (VCI/VaD), mixed diseases including the associated diagnostic challenges of multiple etiology dementias (MED), and issues related to health disparities. The conference complemented the National Institute on Aging’s Alzheimer’s Disease Research Summit 2012: Path to Treatment and Prevention. Both conferences responded to the National Alzheimer’s Project Act that was signed into law in January 2011. The objective of the ADRD conference was to contribute to the efforts directed at preventing and effectively treating Alzheimer’s disease, including Alzheimer’s disease-related dementias, by 2025. The Alzheimer’s Disease-Related Dementias steering committee solicited input from internationally recognized experts to develop prioritized recommendations to guide scientific research in the next 5 to 10 years.

The top ranked basic science recommendation from the ADRD FTD working group targeted the identification and validation of mechanisms associated with tau pathogenesis and related neurodegeneration in FTD. Understanding the mechanism(s) of tau driven neurotoxicity and its relationship to the formation and spreading of tau pathological inclusions is an essential step toward the identification of optimal therapeutic approaches. In particular, research directed at the identification of which pathophysiological events (post-translational tau modifications, aggregation, microtubule dysfunction, interneuronal spread, or other tau (dys)functions) representing the most deleterious and targetable processes in human tau biology, will help to advance our understanding of the disease process and will inform strategies for therapeutic development going forward.

The purpose of this Funding Opportunity Announcement (FOA) is to support a multi-center, interdisciplinary approach that uses innovative, cutting-edge technologies to identify and validate the molecular mechanisms contributing to tau toxicity and associated neurodegeneration characteristic of FTD tauopathies. This multi-center, interdisciplinary approach will be established through a Center without Walls, which will incorporate key scientific expertise in research projects and cores, to drive the identification of the molecular mechanisms associated with tau toxicity and include, through the use of existing government and non-government resources, validation of the relevance of these mechanisms to human tau pathogenesis.

Center without Walls Program:

• It is anticipated that an interdisciplinary research approach will enable the Center without Walls to incorporate expertise from multiple disciplines such as data science, computational biology, structural biology, cell biology, systems biology and molecular biology to develop and validate a new conceptual framework for mechanisms leading to tau toxicity in FTD.
• Center without Walls applications are expected to emphasize novel ideas and approaches, as well as use of state-of-the-art technologies and a team-based approach to achieve stated goals.
• Synergy must be evident among Center research projects and cores, such that successful completion of the aims could not be accomplished without the Center structure.
• Research projects should incorporate innovative approaches, model systems and state-of-the-art technologies that will enable a broad based discovery of mechanisms related to tau toxicity in FTD. Research projects and cores must coordinate efforts, such that data from projects and cores inform each other, as well as the overall direction of the Center. A minimum of three research projects are required.
• Research cores should provide access to technologies and support the development of reagents required by two or more research projects.
• An administrative core is required and should provide overall coordination and support for Center without Walls activities. In addition, the administrative core will be responsible for development and maintenance of a Center website which will inform the broader research community of center activities and resources and data availability.
• A data coordinating core is required and will coordinate the sharing of data generated by the research projects and cores, with the broader research community, through deposition of this data into existing government supported databases, as appropriate.
• Validation of tau toxicity mechanisms and tools developed by the research projects and cores to the human biology of FTD is required and will be coordinated through the human biology validation core which will develop and optimize key assays to test tools developed by the Center without Walls and utilize existing resources and infrastructures to support this validation.

Center without Walls Leadership:

The Center without Walls will be led by an internationally recognized neuroscientist with active, R01-equivalent, independent funding and excellent scientific productivity. The expertise of the Center without Walls Director may be in areas outside of tau biology, if relevant skills can be readily applied to achievement of Center goals. Leadership of the Center without Walls will require coordination with existing government and non-government efforts in FTD research, as well as the utilization of existing resources and infrastructure to advance the validation of tools and mechanisms developed by the Center. Success of the Center without Walls will depend upon strong communication, coordination and integration across its components and external collaborations.

The following activities are not supported under this Center Program:

• An application that includes the following activities will be considered non-responsive to this FOA and would be withdrawn:
• Projects or Cores that support clinical trials or provide patient services. For services associated with clinical research, investigators should contact the NINDS Office of Clinical Research.
• Chemistry or ADME toxicology services associated with candidate therapeutic lead optimization. For services associated with translational research, investigators should consider the NINDS Cooperative Program in Translational Research, and should contact the NINDS Office of Translational Research.

Applicants are strongly encouraged to consult with NINDS Scientific/Research Staff at the beginning of the planning stage of their application (see Agency contacts, Section VIII).

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

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.

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 NIH Intramural Research 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

Projects involving partnerships with industry, small businesses or non-government organizations are encouraged under this FOA. The policy of the NIH is that the results and accomplishments of the activities that it funds and supports should be made available to the public.

Considerations for inclusion of Foreign Institutions under this FOA.

Foreign components of the application must contribute unique scientific expertise, technologies and/or resources to the identification and validation of mechanisms associated with tau toxicity in FTD.

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

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.

The Center without Walls Director (PD/PI) should be an established leader in scientific research with a history of successful funding and proven expertise in the stewardship of large-scale research programs. Center Directors must lead a Project and/or Core within the Center. Other qualifying factors include current research productivity, active funding (NIH R01-equivalent or greater) and the capacity for visionary leadership of an interdisciplinary team. Expertise in areas beyond tau biology is encouraged if the Director’s skills can be applied in novel ways that will stimulate new approaches and the application of new technologies for interrogating the underlying mechanisms of tau toxicity as they relate to FTD.

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

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).

Applicants can access 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.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

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 and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

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:

Margaret Sutherland, PhD
Division of Extramural Research, Neurodegeneration Program Cluster
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5680
Fax: 301-480-1080
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (use for Administrative Core)	6
Core (use for Research Core(s), Data Coordinating Core, and Human Biology Validation Core)	6
Project (use for Research Projects)	12

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

Revision applications must include an Overall component and the components that are affected by the revision. Therefore, the component requirements listed below may not apply to the revision application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Research Core(s): required, minimum of 1
• Human Biology Validation Core: 1 required
• Data Coordinating Core: 1 required
• Research Projects: required, minimum of 3

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Other Attachments: The following information should be uploaded as individual attachments. The filename for each attachment is indicated below; filenames will be used to bookmark the attachments in the application image.

• Center Organizational Structure: a diagram demonstrating interactions among Center components.
• Center Collaborative Organizational Chart: a diagram demonstrating interactions with Center without Walls components and external collaborations

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Introduction to Application: For revision applications, an Introduction to the Application is required in the Overall component.

Specific Aims: Describe the overall aims of the proposed Center without Walls.

Research Strategy: The Overall section states the vision and rationale for the proposed Center without Walls, and provides an overview of integration and synergy of center activities. The Research Strategy should be organized into sections that address Significance, Innovation and Approach.

Significance: Provide a vision statement for the Center without Walls, including expected contributions by the Center, to advancements in the identification and validation of molecular mechanisms involved in tau toxicity related to FTD. Include the overall Center without Walls program objectives and related implementation plan for the proposed award period.

Innovation: Describe how novel approaches, technologies to be applied, investigator expertise, and collaborative activities will advance the goals of the Center without Walls program, including utilization of existing resources and infrastructure that will support the relevance of the tau toxicity mechanisms identified to our understanding of human biology as it relates to FTD.

Approach: Describe the general research framework of the Center. Discuss the proposed research program, highlighting its central theme. Describe the synergy among the Center components, especially the scientific and collaborative approaches that will ensure thematic coherence of Center research and activities. Detailed descriptions of preliminary data should be included within the relevant Research Project and Research Core sections, not in the Overview. For foreign components, included in the application, describe how these components present special opportunities for furthering research advancements through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and are not readily available in the United States (U.S.) or augment existing U.S. resources. Provide evidence that supports the feasibility for the formation and successful implementation of a Center without Walls that encompasses cutting edge technologies, novel approaches and the utilization of existing resources to advance our understanding of the mechanisms associated with tau toxicity and neurodegeneration in FTD.

Letters of Support:

Institutional Commitment (required): Include a letter from a high-level institution official(s) (e.g., Dean of the School of Medicine, Vice President for Research) to confirm institutional commitment to the Center without Walls program. The letter should provide details on how institutional commitment will be established, examples of how the institution maintains and promotes scientific excellence in basic and clinical research, and how the Center without Walls research effort will be prioritized within the institution (relative to other NIH and non-NIH funded programs). Examples of institutional commitment may include, but are not limited to: provision of discretionary resources to the Center without Walls Director, funding for pilot projects, support for recruitment of scientific talent and career enhancement activities, access to institutional infrastructure, cost sharing, assignment of specialized research space, meeting support/space for the bi-annual meetings, and/or other means of support.

Collaboration with other institutional or consortium efforts in FTD or related dementias (required): The letter(s) should describe collaborative efforts and/or opportunities with other institutional programs or consortium efforts in FTD or related dementias. For example, opportunities may exist for collaboration with the NINDS Parkinson's Disease Biomarkers Program (PDBP) which collects longitudinal clinical data and fluid biosamples from healthy controls, and individuals diagnosed with Parkinson's Disease and other Parkinsonisms including Progressive Supranuclear Palsy (PSP). The National Institute of Aging (NIA) funded Alzheimer's Disease Centers collect data on individuals with Alzheimer's Disease and related dementias and this data is available through the National Alzheimer's Coordinating Center (NACC). Support for unique foreign collaborations are allowed in this FOA and an example of non-U.S. based clinical FTD research includes the European Alzheimer's Disease Consortium (EADC), which is a network of over 50 European centers of clinical and biomedical research excellence working in the field of Alzheimer’s disease and related dementias.

Collaboration with national research resources and programs (required): The NIH and other government and nongovernment organizations fund unique resources and programs that encourage: broad data and resource sharing; the development and availability of unique tools for data analysis; and the development and the availability of cutting-edge technologies and data sources that will help advance brain science. Examples of these resources include, but are not limited to: 1) the NIH Library of Integrated Network-based Cellular signatures (LINCS); 2) the NINDS Human Cell and Data Repository (NHCDR) which offers reprogramming and gene editing services of iPSC line development, as well as FTD and control human fibroblast and iPSC cell lines; 3) the NINDS Biomarkers Repository (BioSEND) which contains FTD biofluid biosamples and biosamples for other neurological diseases; 4) the NIA National Repository for Alzheimer's Disease (NCRAD) which contains FTD and Alzheimer's Disease biofluid biosamples; 5) the NIH NeuorBioBANK; and 6) the Allen Brain Atlas. The letter(s) should describe collaborative efforts and/or opportunities with these national research resources and programs.

Collaboration with other, large-scale FTD-related clinical research projects (required): Collaborations with NIH and other government funded large-scale FTD-related research projects will help to minimize the costs associated with validating the mechanisms of tau toxicity identified in model organisms to the human biology associated with FTD. Such large-scale FTD-related clinical research projects include, but are not limited to: 1) the Longitudinal Evaluation of Familial FrontoTemporal Dementia Subjects (LEFFTDS) study, part of the NIH Rare Disease Clinical Research Network (RDCRN); 2) the Advanced Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) study; and 3) the European Genetic FTD Initiative (GENFI). The letter(s) should describe the collaborative efforts and/or opportunities to utilize data and resources provided by the large-scale FTD-related clinical research projects. Data and resource sharing should be bi-directional.

Collaboration with Nongovernmental Organizations and philanthropic entities (required): Nongovernmental patient advocacy organizations have common goals for improving treatment and understanding causes of FTD. Letter(s) should detail planned or ongoing partnerships between members of the Center without Walls (Director and/or Research and Core Lead(s)) and these groups. The letter(s) should also outline, where appropriate, any additional resources that will be provided by the nongovernmental organizations and philanthropic entities.

Collaboration with NIH Intramural Researchers (if applicable): Include a letter from the Scientific Director of the collaborating NIH Institute or Center. The letter must describe the role of intramural staff, and specify the nature and amount (funding) of NIH intramural resources to be allocated to the proposed project. In addition, the letter should state that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research (if applicable).

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, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan and Resource Sharing Plan. The Data Sharing Plan should include a Center without Walls website that provides information to the broader research community.

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.

When preparing your application in ASSIST, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Budget for the following Center without Walls-specific activities should be included in the Administrative Core:

• Biannual Center without Walls Meetings: Include meeting room rental, audiovisual support, travel and lodging costs for the Center Director, Center Administrator, and Project and Core Leads to attend the biannual center without walls meetings. To promote efficient spending, budgeted costs for EAC member travel will be within range of local per diem rates (as per General Services Administration (GSA) guidance) and follow general NIH guidelines for travel and expense reimbursement rates.
• External Advisory Committee (EAC): Include all EAC-related costs (meeting and travel) in the proposed budget. To promote efficient spending, budgeted costs for EAC member travel will be within range of local per diem rates (as per General Services Administration (GSA) guidance) and follow general NIH guidelines for travel and Note the EAC committee members should not be identified until after funding decisions are made and at that time, the EAC membership should be determined in collaboration with NINDS program staff expense reimbursement rates.
• Center Website: Include all costs for the development and maintenance of a Centers without walls Website. Related costs for development of social media outreach strategies may also be included.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For revision applications, an Introduction to the Application is allowed for each component.

Specific Aims: Describe the goals and planned activities of the Administrative Core

Research Strategy: Organize the Research Strategy into sections on Significance, Innovation and Approach.

Significance: Describe how the Administrative Core will serve as the organizational foundation for research activities of the Center without Walls, as well as how the Core will effectively support Center service as a national and international resource for FTD research related to tau biology. Justify the proposed interdisciplinary research strategy governance, including coordination with foreign institutions and other funding entities.

Innovation: Describe how the Administrative Core utilizes novel approaches to maximize synergy among Center without Walls investigators, and fosters relationships with the broader research and advocacy communities.

Approach: Describe the proposed activities of the Core, including but not limited to the following:

• Promote the integration and function of Center components and activities.
• Provide support for the Center Director in oversight of Center governance.
• Provide support for the Center Director in oversight of external collaborations that support Center research projects and/or cores through provision of existing resources or infrastructure.
• Provide support for the Center Director in management of Center without Walls committees and cores including but not limited to the Executive Steering Committee, the Data Coordinating Core and the Human Biology Validation Core.
• Organize biweekly meetings of the Center Executive Steering Committee, and monthly meetings of the Data Coordinating Core and Human Biology Validation Core.
• After funding decisions have been made, work with NINDS program staff to identify an External Advisory Committee.
• Organize timely meetings of the External Advisory Committee.
• Maintain an accounting of resource generation and related utilization, and steps taken to maximize the research utilization of these resources within and beyond the Center without Walls.
• Provide advance notice of manuscripts and publications to the NINDS program officer; work with the NINDS Office of Communications on press releases highlighting Center accomplishments.
• Prepare and submit annual progress reports.
• Provide assurance of compliance with NIH policy requirements.
• Establish and maintain the Center's website.

Provide a Scientific Governance Structure that includes:

Description of the general composition and function of the external and internal committees that will provide scientific governance for the Center without Walls. Committees should include (but are not limited to:

1) External Scientific Advisory Committee;

2) Executive Steering Committee made up of the Center without Walls Director, NIH program staff, and PIs for Research projects and cores and external collaborators;

3) Data coordinating committee;

4) Clinical oversight committee

Letters of Support: Only letters of support specific to this component should be attached to this section.

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, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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.

Not Applicable

Not Applicable

When preparing your application in ASSIST, use Component Type Core.

Each Research Core must be essential and support key tool/model development for at least two or more Research Projects.

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

SF424 (R&R) Cover (Research Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Core)

List all performance sites that apply to the specific component.

Research & Related Senior/Key Person Profile (Research Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.

The Core Lead must have appropriate expertise, as well as a record of productivity and collaboration, to ensure success of the Core. The expertise of the Core Lead may be in areas outside of tau biology, if relevant skills can be readily applied to achievement of Center goals.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

Budget (Research Core)

Budget forms appropriate for the specific component will be included in the application package. Use of existing research resources and programs are encouraged through the establishment of appropriate subcontracts with those entities.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Core)

Introduction to Application: For revision applications, an Introduction to the Application is allowed for each component.

Specific Aims: Describe the goals and planned activities of the Research Core, as well as its essential relationship to the Aims of at least two Research Projects.

Research Strategy: Organize the Research Strategy into sections on Significance, Innovation and Approach.

Significance: Describe the essential relationship of the Research Core to at least two proposed Center without Walls Research Projects, the means through which this Core will advance the aims of each associated project, and what and how resources generated will be made available to the broader research community.

Innovation: Describe how the innovative technologies and development of shared resources will advance our understanding of the underlying molecular mechanisms driving tau toxicity and related neurodegeneration associated with FTD.

Approach: Indicate percent usage by proposed Research Projects.

Research Core approaches may include, but are not limited to:

• Development of antibodies and other reagents to support research projects
• Support for omic (transcriptomics, proteomics, metabolomics, epigenomics) analyses of model systems and postmortem human tissue
• Isolation from human tissue or chemical synthesis of tau isoforms
• Generation of unique model systems
• Use of existing infrastructures for iPSC cell line generation and editing, as provided by the NINDS Human Cell and Data Repository
• Whole genome sequencing or other genotyping approaches of genome-modified model systems including human iPSC lines and derivatives
• Use of existing infrastructures for iPSC and iPSC differentiated cell type analysis as is provided through the NIH NeuroLINCS program
• Microscopy including but not limited to confocal imaging, robotic imaging
• Structural biology support for NMR, CryoEM and CryoET

Research Core approaches cannot include the following:

• Hypothesis- or discovery-driven Aims.

Letters of Support: Only letters of support specific to this component should be attached to this section.

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, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• All human iPSC lines generated are expected to meet the NINDS criteria for banking and distribution outlined in NOT NS-14-032

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.

PHS Inclusion Enrollment Report (Research Core)

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

When preparing your application in ASSIST, use Component Type Core.

The Human Biology Validation Core will support the validation of tau reagents/resources developed by the Center without Walls components (projects and cores) to human FTD biology using existing government supported resources and infrastructure.

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

SF424 (R&R) Cover (Human Biology Validation Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Human Biology Validation Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Human Biology Validation Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Human Biology Validation Core)

List all performance sites that apply to the specific component.

Research & Related Senior/Key Person Profile (Human Biology Validation Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.

The Core Lead must have appropriate expertise in assay development and optimization and analysis of human fluid biosamples and post mortem tissue, as well as a record of productivity and collaboration, to ensure success of the Core and its utilization within the Center without Walls program. The expertise of the Core Lead may be in areas outside of FTD or tau biology, if relevant skills can be readily applied to achievement of Center goals.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

Budget (Human Biology Validation Core)

Budget forms appropriate for the specific component will be included in the application package.

The Center without Walls Human Biology Validation Core budget should include the following:

• Funds to obtain biospecimens, including postmortem tissues and data from existing government supported biorepositories and resources for direct use and support of the Center without Walls human validation efforts; the NINDS will not, however, provide funds to support infrastructure for prospective brain or biospecimen banking efforts in the Center without Walls Program.
• To collaborate with existing institutional or consortium efforts in FTD and related dementias, establishment of a subcontract with the entity to support the resources or services to be utilized in the collaboration is encouraged.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Human Biology Validation Core)

Introduction to Application: For revision applications, an Introduction to the Application is allowed for each component.

Specific Aims: Describe the subject population and related clinical data and biospecimens to be collected.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

Significance: Describe contributions of the Human Biology Validation Core to the goals of the Center without Walls and its integration with the Centers Research Projects and Cores.

Innovation: Describe how innovations in assay development and optimization, sample preparation will advance the validation process for tau toxicity mechanisms identified through the Center without Walls research projects and cores.

Approach: Describe the proposed activities of the Human Biology Validation Core which may include, but are not limited to, the following:

• Collaboration with existing consortium or programs such as, but not limited to: 1) the Longitudinal Evaluation of Familial FrontoTemporal Dementia Subjects (LEFFTDS) study, part of the NIH Rare Disease Clinical Research Network (RDCRN); 2) the Advanced Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) study; 3) the European Genetic FTD Initiative (GENFI) and the NINDS Parkinson's Disease Biomarker Program (PDBP) which includes data and biosamples from healthy controls, PD, PSP and CBD patients. These collaborations may involve ancillary studies where specific biospecimen types or collection procedures are required for human validation assays.
• Acquisition and utilization of existing high quality biosamples or postmortem tissue and corresponding clinical data from NIH sponsored and other government and nongovernment biorepositories such as, but not limited to: 1) the NINDS Biomarkers Repository (BioSEND) which contains FTD biofluid biosamples and biosamples for other neurological diseases; 2) the NIA National Repository for Alzheimer's Disease (NCRAD) which contains FTD and Alzheimer's Disease biofluid biosamples; and 3) the NIH sponsored NeuroBioBANK
• Development and optimization of assays relevant to human biology for validation of mechanisms and targets identified by the Center without Walls.
• Utilization of cutting-edge technologies for analysis of human biofluid biosamples or postmortem tissues acquired through collaborations with existing consortium and resources
• Application of quality assurance measures for assay standardization

To enable identification of resources used and the broad sharing of datasets generated from shared resources:

• A global unique identifier (GUID) must be associated with each biosample or tissue sample utilized.
• Samples utilized must have accompanying patient consents that allow for broad data sharing with both industry and academic investigators

Activities not supported through the Human Biology Validation Core include:

• Establishment of de novo patient cohorts
• Development of a biosample and/or data repository

Letters of Support

Requirements if ancillary study(s) in collaboration with an existing parent study are required:

If an ancillary study in collaboration with an existing parent study is proposed, The Center without Walls Human Biology Validation Core Director must provide documentation from the collaborating parent study PD(s)/PI(s) of approval to use the existing study infrastructure, participants, and other data from the parent study. For ancillary studies involving collection of additional clinical data or biospecimens, wherein these biospecimens do not exist and are required for validation of tau toxicity mechanisms or targets identified by projects or cores of the Center without Walls, a brief description of the ancillary study proposed, the number of collaborating parent study participants required for the study, the number of collection time points and a statistical analysis plan must be submitted to the collaborating parent study PD(s)/PI(s) for approval, prior to submission of an application in response to this FOA and must be documented by a letter of support. Ancillary studies must not interfere with the parent study or unduly burden participants. Approved procedures and policies from the parent study must be followed.

Only letters of support specific to this component should be attached to this section.

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, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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.

PHS Inclusion Enrollment Report (Human Biology Validation Core)

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

When preparing your application in ASSIST, use Component Type Core.

The data coordinating core will ensure that data generated by the Center without Walls components (projects and cores) is available to the broader research community through existing and established government supported databases

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

SF424 (R&R) Cover (Data Coordinating Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Data Coordinating Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Coordinating Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Data Coordinating Core)

List all performance sites that apply to the specific component.

Research & Related Senior/Key Person Profile (Data Coordinating Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.

The Data Coordinating Core Lead must have appropriate expertise, including familiarity with existing government sponsored databases and the corresponding data formats and submission requirements, as well as a record of productivity and collaboration, to ensure success of the Core. The expertise of the Core Lead should be in the areas of data science and/or computational biology.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

Budget (Data Coordinating Core)

Budget forms appropriate for the specific component will be included in the application package.

Use of existing databases, resources and tools are encouraged through the establishment, when appropriate, of subcontracts with those entities.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Data Coordinating Core)

Introduction to Application: For revision applications, an Introduction to the Application is allowed for each component.

Specific Aims: Describe the data types to be generated by the Center without Walls projects and research cores and data repositories to be used for data sharing with the broad research community.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

Significance: Describe contributions of the Data Coordinating core to the data sharing goals of the Center without Walls.

Innovation: Describe how the activities of the Data Coordinating Core will incorporate innovative data analysis and data sharing activities through the use of existing datasets and databases, respectively.

Approach: Describe the proposed activities of the Data Coordinating Core which may include, but are not limited to, the following:

• Integration of existing metadata standards for sharing of omic datasets generated by the Center without Walls Research Projects and Cores.
• Development of metadata standards for datasets not currently covered by existing databases and programs
• Prioritization of existing databases to be used and creation of a Center without Walls identifier that will enable linking of Center generated datasets
• Regular deposition of omic datasets generated by Center without Walls Research Projects and Cores with appropriated government-sponsored data repositories such as, but not limited to: 1) the Database for Genotypes and Phenotypes (dbGaP); 2) the NIH Gene Expression Omnibus (GEO) repository; and 3) the NIH LINCS BD2K Data Coordination and Integration Center.
• Development of data analytical tools for large diverse datasets generated by the Center projects and cores when existing tools are not available
• Development of machine learning approaches for analysis of large datasets
• Utilization of existing data analytical tools and approaches for handling of iPSC and iPSC-derived cell types as available through the NIH LINCS program.
• Integration of existing government and nongovernment sponsored datasets from data repositories such as, but not limited to: The Human Epigenome Atlas; 2) NIH LINCS datasets; 3) the PRoteomics IDEntifications (PRIDE) database at the European Bioinformatics Institute; 4) NIH Genotype-Tissue and Expression (GTEx) program; 5) the NIH Gene Expression Omnibus (GEO) repository; 6) the NINDS Parkinson's Disease Data Management Resource; 7) the NIA-sponsored National Alzheimer's Disease Coordinating Center (NACC) and 8) the Allen Brain Atlas.
• Development of aggregate data display tools for the Center website
• Provision of statistical analyses for Center projects and cores

Activities not supported by the Data Coordinating Center

• Development of an independent database for the Center without Walls

Letters of Support: Only letters of support specific to this component should be attached to this section.

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, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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.

Include the following information:

PHS Inclusion Enrollment Report (Data Coordinating Core)

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

When preparing your application in ASSIST, use Component Type Project.

Research projects are hypothesis-driven investigations designed to elucidate tau toxicity mechanisms in FTD. Basic research may utilize omic and other approaches for the identification of these mechanisms in model systems. However, while serving as the basis for discovery, mechanisms identified must be validated for their relevance to human biology through interaction with the Centers without Walls Human Biology Validation Core. Research projects within the Center without Walls must be coordinated with each other, so that data from one project informs the activities and directions of another.

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

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Project)

List all performance sites that apply to the specific component.

Research & Related Senior/Key Person Profile (Research Project)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.

The Project Lead must demonstrate active, R01-equivalent, independent funding and excellent scientific productivity. The expertise of the Project Lead may be in areas outside of tau biology, and especially in areas where innovative technologies are being applied to genome-wide screening and editing in model organisms, if relevant skills can be readily applied to achievement of Center goals. Collaborations with Early Stage investigators or New investigators, or those investigators in the early stages of independent careers are encouraged.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

Budget (Research Project)

Budget forms appropriate for the specific component will be included in the application package.

Investigators are encouraged to develop multi-institutional, integrative research projects which will accelerate the discovery of the molecular mechanisms for tau toxicity as they relate to FTD by incorporating innovative technologies and approaches into their research plans. For research projects, discovery is the focus of the research through the use of existing or new model systems that have demonstrated relevance to FTD disease pathogenesis.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Project)

Introduction to Application: For revision applications, an Introduction to the Application is allowed for each component.

Specific Aims: State the aims of the basic research project and the hypotheses to be tested.

Research Strategy: Organize the Research Strategy into sections on Significance, Innovation and Approach.

Significance: Describe the contributions of the research project to the goals of the Center without Walls. Explain why the Center structure is required to accomplish proposed aims. Describe and justify the innovative research approach. Address how successful completion of proposed studies will advance our understanding of molecular mechanisms involved in tau toxicity and related neurodegeneration.

Innovation: Provide evidence that use of novel concepts, models, research approaches and/or techniques will contribute to the discovery of the molecular mechanisms of tau toxicity.

Approach: Describe the experimental approaches and model system(s) utilized to address the specific aims. Examples of research project topics and/or approaches include, but are not limited to, the following:

• Application of innovative omic approaches in model systems to identify molecular mechanisms of tau toxicity
• Application of innovative genome-wide approaches to identify and test mechanisms of tau toxicity
• Identification of shared molecular mechanisms of tau toxicity across model systems
• Use of innovative structural biology approaches to understand how human disease causing mutations in the tau gene (MAPT), post-translational modifications, alternative exon usage, or tau species affect tau protein structure and function
• Application of innovative approaches to study tau transmission in model system
• Use of systems biology approach to integrate data from various data sources including but not limited to omics datasets, clinical datasets, structural biology data sets, etc.
• Research approaches that address FTD cell-type specificity in relation to tau toxicity
• Research approaches using human cell systems to compare the cellular phenotypes originating from various MAPT disease-causing mutations and their impact on tau protein function.
• Utilization of data from the Human Biology Validation Core to test potential tau toxicity mechanisms in model systems

Include a milestone plan that identifies a timeline for deliverables, interaction with supporting research cores and data and resource sharing as appropriate.

Explain how the research project will coordinate activities with the Center without Walls supporting research core, human biology validation core and data coordinating core. The research strategy should include how molecular mechanisms identified will be prioritized for validation by the Human Biology Validation Core. The research strategy should also include alternative approaches for innovative, but high risk research approaches.

Provide a strong biological rationale for the intended approach. The NINDS urges applicants to consider the rationale for the chosen model(s) and endpoints, adequacy of controls, justification of sample size, statistical methods, blinding methods, strategies for randomization, and robustness and reproducibility of results. Where appropriate, potential conflicts of interest should be noted when describing supporting data and designing the proposed studies. Applicants are strongly urged to address these criteria when describing supporting data and designing the proposed studies (as appropriate).

Letters of Support: Only letters of support specific to this component should be attached to this section.

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, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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.

PHS Inclusion Enrollment Report (Research Project)

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

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.

See Part 1. 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. Overview Information 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) using ASSIST or other electronic submission systems. 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 Policy on Late Application Submission.

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.

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.

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

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads 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.

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 (SAM). 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.

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.

An Applicant Technology and Resource Webinar will be scheduled to provide information about new technologies and resources available to prospective applicants. Overviews of emerging technologies will be provided by experts in the respective fields and resource descriptions will be provided by representatives for these resources. NIH staff will provide an overview of the FOA and answer questions. The webinar is open to all prospective applicants. Participation in the teleconference is not a prerequisite for applying, and is not required for a successful application. Information about how to participate in the webinar will be posted at http://www.ninds.nih.gov. Potential applicants are encouraged to submit their questions or comments to [email protected] prior to the meeting. Afterwards, the webinar slides and a summary of the questions and answers will be posted on the same site. NIH will also post a list of Frequently Asked Questions (FAQs) and answers; this information may be updated without additional notice.

In order to expedite review, applicants are requested to notify the NINDS Program Officer 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.

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

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.

For this particular announcement, note the following:

• Synergy: Each U54 application will be reviewed for the contribution the scientific project or core makes to the overall composition of the Center Without Walls, as well as the synergy between the scientific projects and core(s).
• Utilization of existing infrastructure: Each U54 application will be reviewed for the utilization of existing infrastructure and resources that are required by the Center without Walls to advance discovery and validation of mechanisms related to the human biology of tau toxicity associated with FTD. It is anticipated that the use of existing infrastructure and resources will accelerate activities proposed within the Center without Walls while reducing or eliminating the necessity and costs associated with setting up these resources de novo.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Center without Walls 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 Center Without Walls proposed).

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

Does the Center without Walls address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the Center without Walls 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 proposed Center without Walls utilize existing and emerging technologies to identify and validate mechanisms of tau toxicity related to FTD? Does the proposed Center without Walls test the relevance of the basic mechanisms identified by the research projects, to human biology? Is the resource development proposed relevant to the broader dementia research community? Is there strong evidence that the proposed Center without Walls will advance research in tau toxicity mechanisms related to FTD, through both its scientific projects and cores?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center without Walls? 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?

Reviewers will consider the following during evaluation of the Center without Walls Director:

Will the Center without Walls Director provide visionary scientific leadership for the Center? Does the Director have appropriate leadership experience, including leadership of a large-scale research program, which predicts success of the Center? Is the Director an established leader and innovator with a history of successful funding, as well as currently active funding? Has the Director made an appropriate time commitment to the Center, including leadership of a project and/or core? If the Director’s primary area of expertise is in an area other than tau biology, is it clear that the Director’s skills can be applied in novel ways to the advancement of mechanisms of tau toxicity as it relates to FTD?

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?

During evaluation of the proposed Center without Walls applications, reviewers will consider the level of innovation specifically related to state-of-the-art tau biology research, including the following: Does the application outline novel approaches to advancing the stated goals of the proposed Center without Walls, i.e., will the proposed research advance understanding of mechanisms driving tau toxicity in FTD? Are the proposed projects likely to make major rather than incremental advances toward this goal?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center without Walls? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the Center without Walls 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?

Are letters of support included for access to existing resources or programs?

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?

Are there appropriate plans for communication and collaboration to support the Center without Walls function and goals?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for each research project to exert a sustained and powerful influence on understanding of mechanisms of tau toxicity related to FTD, based on consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

How will the project contribute to the overall success of the Center without Walls? Will the proposed research result in major rather than incremental advances in understanding of mechanisms of tau toxicity related to FTD?

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?

Does the project lead have a productive record of bringing novel and significant projects to fruition as an independent principal investigator? If the investigator does not have current NIH funding, does s/he have active, independent funding that is the equivalent of an NIH R01? Is sufficient investigator effort dedicated to the research project and Center activities?

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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center without Walls? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Does the project challenge existing paradigms, address an innovative hypothesis or critical barrier to progress in the field? Is the work proposed appropriate to the expertise of the PD/PI and other researchers?

Does the research project show evidence of rigor in terms of rationale, preliminary data, experimental design and strategies to minimize bias?

Are the milestone plan deliverables appropriate for the project and interaction with the Center without Walls supporting research cores, data coordinating core and human biology validation core?

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?

Review Criteria for Administrative Core

The Administrative Core will receive a single score that reflects the following criteria:

• Is there a clear, detailed leadership plan for managing the Center without Wall’s research and administration, ensuring appropriate prioritization of research, needed course corrections and problem identification and resolution, and effective sharing of resources, that conveys a high likelihood of effective, productive management of the Center Without Walls as a whole?
• Are the core personnel qualified and experienced in the administration of a large, multi-component research program?
• Is there an organizational structure and charter that will facilitate coordination, integration and timely evaluation of activities and progress?
• Are there internal and external procedures for monitoring and evaluating the proposed research projects and core facilities/resources? Are there appropriate plans for management of data, animal models and other resources?
• Are there plans for the utilization, as appropriate, of current NINDS-funded resources such as biospecimens available through the NINDS BioSEND Repository, or the NIA-funded NCRAD repository?
• Does the approach for the Administrative Core include a system for tracking resource generation and related utilization, as well as the identification of what steps are taken to maximize the research utilization of these resources within and beyond the Center without Walls?
• Are plans for the development and maintenance of a Center without Walls website outlined and sufficiently described?

Review Criteria for Research Core(s)

Each Core must provide essential functions or services for at least two projects. Each resource core will receive a single score that reflects the following criteria:

• Is the proposed resource core well matched to the needs of the overall program? Does it provide essential facilities or services for two or more research projects?
• What is the overall quality of the proposed core services? Are adequate quality control processes proposed for the facilities or services provided by the Core (including procedures, techniques, and quality control)? What are the criteria for prioritization and usage of Core products and/or services?
• Are the qualifications, experience, and commitment of the leader(s) of the Core and other key personnel adequate and appropriate for providing the proposed facilities or services?
• Will the proposed Core provide cost effective services to the Program?
• Is the environment for the Core adequate to support the program as proposed?

Review Criteria for Data Coordinating Core

• Is the Data Coordinating Core essential for the support of the proposed Center without Walls program?
• Does the Core Leader have the appropriate expertise and seniority to direct the proposed Data Coordinating Core facility? Is the Core leader knowledgeable in data standards and requirements for use of existing government sponsored databases identified in the application? Are there appropriate plans for the rigorous management and quality control of any research data contributed by Center research projects and cores?
• Does the Core leader have experience in the development and or use of data analytical tools for large diverse datasets generated by the Center projects and cores?
• Does the approach outlined for the Data Coordinating Core include development of aggregate data display tools for the Center website?
• Does the approach outlined for the Data Coordinating Core support statistical analysis for Center research projects and cores?
• Does the approach outlined for the Data Coordinating Core support the integration of existing government and nongovernment sponsored datasets from data repositories to enhance data analysis by Center research projects and cores?

Review Criteria for Human Biology Validation Core

• Is the Human Biology Validation Core essential for the support of the proposed Center without Walls program?
• Does the Core Leader have the appropriate expertise and seniority to direct the proposed Human Biology Validation Core facility? Are there appropriate plans for the rigorous management and quality control of any research data or materials to be obtained from human subjects? For the use of existing biosample and autopsy tissue resources, is the patient cohort well-defined and appropriately diverse?
• If appropriate, do ancillary studies match the requirements of the parent study and does the ancillary study minimize any additional burden to parent subject participants?

As applicable for the Center Without Walls t 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.

Milestone Plans

Are the milestone plans appropriate for the stage of the project? For early stage projects, are there clear milestones that allow for adjustments to the planned research and define a timeline for evaluation should roadblocks be encountered that cannot be overcome?

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.

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.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Not Applicable

Not Applicable

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 Center without Walls 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.

Not Applicable.

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).

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 Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by NINDS in accordance with NIH peer review 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 National Advisory Neurological Disorders and Stroke 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.
• Compliance with data and resource sharing policies

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.

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.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that 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 FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 Part 75, 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:

• Determining experimental approaches, designing protocols, setting project milestones and conducting experiments;
• Adhere to existing Center without Walls study policies regarding data and biospecimen sharing and other policies that might be established during the course of this activity;
• Report to NINDS Scientific Program staff regarding timeline and milestone achievement during the course of the project, as delineated in the terms and conditions of award;
• Submit annual progress reports during the funding period, in a format as agreed upon by NINDS program staff;
• Accept and implement any other common guidelines and procedures developed for the Center without Walls program and approved by NINDS program staff;
• Coordinate with other clinical projects focused on FTD including but not limited to NIH-funded LEFTDS and ARTFL studies , including sharing of data with a centralized data management resource;
• Attend in-person Center without Walls meetings to be held biannually and organized in collaboration with NINDS program staff where PD(s)/PI(s) will present up to date findings (including unpublished results) on ongoing projects. The cost of these meetings will be covered under the current funding for this application.
• Awardees are expected to make new information and materials known to the research community not only in the bi-annual Tau Center without Walls meetings but also in a timely manner through publications, web announcements, reports to NINDS program staff, and other mechanisms.
• Participate on Tau Center Without Walls executive steering committee
• 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.

Publications:

• The PD(s)/PI(s) will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The PD(s)/PI(s) and Project Leaders are requested to submit manuscripts to the NIH Project Scientists within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the PD(s)/PI(s) and appropriate Project Leaders and will require appropriate acknowledgement of NINDS and Tau Center without Walls support. Timely publication of major findings is required.
• NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
• NINDS program staff will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination. However, the role of NINDS Project Scientists will be to facilitate and not to direct the activities.

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

• NINDS program staff will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination. However, the role of NINDS Project Scientists will be to facilitate and not to direct the activities.
• Contribute to the adjustment of research protocols, project milestones or approaches as warranted;
• Serve as a liaison between the awardees, the NINDS Advisory Council and the larger scientific community;
• Coordinate the efforts of the awardees with others engaged in FTD research, including other awardees funded by related NIA, NINDS and NCATS programs;
• Serve on an Tau External Liaison Group as appropriate;
• Serve on the Tau Executive Steering committee,
• Assist in promoting the availability of data and resources developed in the course of this project to the scientific community at large;
• Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
• Retain the option to recommend the withholding or reduction of support from any cooperative agreement that either substantially fails to achieve its goals according to the milestones agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award including biospecimen and data sharing requirements.
• Additionally, an NINDS program official or NINDS program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

None; all responsibilities are divided between awardees and NIH staff as described above.

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.

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.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 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)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Margaret Sutherland, PhD)
National Institute for Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5680
Email: [email protected]

Chief Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-4188
Email: [email protected]

Tijuanna E. DeCoster, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: [email protected]

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 45 CFR Part 75.