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 using ASSIST or an institutional system-to-system solution; paper applications will not be accepted.

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

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

Purpose

The purpose of the Lewy Body Dementia Center Without Walls (CWOW) program is ultimately to understand how toxic species of alpha-synuclein and amyloid-beta produce the clinical pathology characteristic of Lewy Body Dementia. This FOA invites applications that will systematically and comprehensively characterize alpha-synuclein and amyloid-beta subspecies found in human LBD post-mortem brain tissue, identify toxic subspecies and potential mechanisms of toxicity, and characterize any interactions between the proteins that may contribute to increased toxicity and/or explain selective vulnerabilities of cells/circuits. Given the heterogeneity of both alpha-synuclein and beta-amyloid subspecies, applicants will be expected to focus on the use of post-mortem brain tissue from subjects with LBD; human neuronal cultures/slices/organoids, and human blood/stem cells/CSF from subjects with LBD may also be used for this purpose. It is expected that a multi-site, multidisciplinary team with expertise in 1) mapping neuronal protein structure, function, and interactions at multiple levels, and 2) elucidating neurodegenerative mechanisms that are likely to be relevant to LBD, will be necessary. All centers will be expected to produce a publicly-available library of fully characterized alpha-synuclein and amyloid-beta subspecies found in LBD.

Background

The National Alzheimer's Project Act (NAPA) was passed in 2011 with a primary research goal aimed at finding a way "to prevent and effectively treat Alzheimer's by 2025." Since then, the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS) have held multiple research summits to assess the needs and opportunities relevant to this goal for Alzheimer's Disease and Alzheimer's Disease Related Dementias. In particular, the NINDS has convened expert panels in 2013 (https://www.ninds.nih.gov/About-NINDS/Strategic-Plans-Evaluations/Strategic-Plans/Alzheimers-Disease-Related-Dementias) and again in 2016 (https://www.ninds.nih.gov/News-Events/Events-Proceedings/Events/Alzheimers-Disease-Related-Dementias-Summit-2016) that were tasked with recommending research priorities for advancing the state-of-the-science for the Lewy Body Dementias as well as other types of dementias. During both summits, panel members identified critical new research targets and tools that will be essential for understanding and developing treatments for these disorders. Panel members emphasized the need to systematically characterize disease-specific changes in LBD brain tissue so that underlying disease mechanisms could be identified and used to guide future biomarker and therapeutic approaches.

LBDs, which include Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD), present clinically with the motor symptoms typical of Parkinson's disease (PD) in addition to cognitive deficits as may be seen in Alzheimer's disease (AD). This combined clinical picture is reflected in the neuropathology, which in LBD is characterized by the accumulation of alpha-synuclein in Lewy Bodies (as seen in PD) and amyloid-beta in amyloid plaques (as seen in AD). To a lesser extent, the tau in neurofibrillary tangles (as seen in AD) may also be seen in LBD tissue. In PD, AD, and LBD, these abnormal proteins accumulate in many of the same brain regions; however, they are also found in some regions that are relatively unique in LBD (e.g., Lewy bodies in the cortex).

The normal functions of amyloid precursor protein and alpha-synuclein are poorly understood. Both proteins are amyloidogenic and capable of aggregating into oligomers, amyloid fibrils and beta sheets; however, for both proteins, aggregates exhibit substantial heterogeneity in composition and structure. This heterogeneity makes it difficult to answer key questions about which specific subspecies are neurotoxic, which conditions promote the formation of neurotoxic subspecies, how the proteins cause neurotoxicity, and why some brain regions are more susceptible to neurotoxic aggregation than others. It may also slow the development of diagnostics (e.g., PET ligands) and treatments (e.g., pharmaceuticals), since these are typically based on a clear knowledge of target protein structure. In general, more work has been done to answer these questions for amyloid-beta aggregates than for alpha-synuclein aggregates, and almost none of this work has been done specifically in LBD. Even less is known about whether the co-occurrence of both types of abnormal aggregates, as seen in LBD, is simply coincident or is due to some common mechanism/vulnerability. Since both types of aggregates are present in patients with LBD (i.e., the same "brain tissue environment"), this disease may present a unique opportunity for comparing and defining neurotoxic aggregate subspecies, mechanisms, and selective regional vulnerabilities.

Specific Research Objectives and Requirements:

Applications to this FOA will be expected to focus on identifying and cataloging alpha-synuclein and amyloid-beta subspecies found in human LBD post-mortem brain tissue and characterizing their potential mechanisms of neurotoxicity. Human neuronal cultures/slices/organoids, and human blood/stem cells/CSF from subjects with LBD may be used in addition to post-mortem brain tissue. Each LBD CWOW application should propose an overall hypothesis to explain not only how neurotoxicity is induced by these aggregates, but how these aggregates and their mechanisms of toxicity might interact with each other and/or contribute to selective vulnerabilities of cells and circuits. All proposed projects and cores for the CWOW must collaborate seamlessly to address this overall hypothesis; applicants will be expected to clearly describe how each component synergizes with the others and justify why each is necessary to achieve the overall CWOW goal. At least 3 projects must be proposed.

Depending on the overall hypothesis of the CWOW, its component projects might seek to address one of these areas of interest (among others):

Determining the metabolic, signaling or (epi)genetic factors that contribute to the transformation from normal to abnormal proteins in LBD.

Delineating the unique structural/functional characteristics of abnormal alpha-synuclein and beta-amyloid in LBD compared to those in related disorders (e.g., PD, AD).

Identifying neuronal mechanisms for processing abnormal proteins and the conditions under which these become altered, inadequate or overwhelmed in LBD.

Elucidating differences and similarities in how alpha-synuclein and beta-amyloid are processed by neurons within the same LBD brain tissue.

Elucidating differences and similarities in how alpha-synuclein and beta-amyloid are processed by neurons in LBD brain tissue versus brain tissue from other neurodegenerative disorders.

Elucidating regional differences and similarities in how alpha-synuclein and beta-amyloid are processed by neurons within the same LBD brain tissue (i.e., identifying conditions predisposing to regional vulnerabilities).

Determining mechanisms by which pathology progresses from one brain region to another in LBD.

Examining whether toxic subspecies of alpha-synuclein and beta-amyloid interact to promote or accelerate neurotoxicity in LBD.

Since the structure of both alpha-synuclein and beta-amyloid are notably heterogeneous, applicants will be expected to focus on the use of human tissue in all projects. All CWOW applications must include a letter of collaboration/support from an existing brain tissue repository with post-mortem brain tissue from patients with LBD sufficient to support the needs of the projects. All LBD brain tissue must meet standard diagnostic criteria for DLB or PDD (e.g., DLB Consortium/McKeith criteria). The collection of new post-mortem brain tissue, blood, or CSF will be allowed if needed to support projects that propose innovative uses of fresh human tissue (e.g., human neuronal slices, human primary neuronal cultures, neuronal organoids, etc.); such projects are encouraged. If previously collected pre-mortem human blood, CSF or stem cells will be used, clear details on how the specimens were processed and stored must be provided. For any newly collected samples, applicants are encouraged to follow protocols established by the Parkinson's Disease Biomarker Program (PDBP) or the Alzheimer's Disease Neuroimaging Initiative (ADNI) for biospecimen collection and storage.

Centers with a primary or substantial focus on understanding alpha-synuclein or beta-amyloid in the context of neurodegenerative diseases other than LBD, or on the use/development of animal models, will be considered nonresponsive. Development of new brain banks/tissue repositories will also be considered nonresponsive. The use of non-human tissue or immortalized cell lines would only be considered acceptable if used for secondary validation and if strongly justified.

LBD CWOWs are expected to involve collaborations between multiple investigators at multiple sites in order to maximize: 1) access to cutting-edge technologies, 2) use of the highest quality resources, and 3) opportunities for innovation in research ideas and design. CWOW applications centered at a single research site will be considered nonresponsive. Given the scope of this research challenge, it is anticipated that applicants will need to assemble a world-class scientific team with expertise in a broad range of research areas, such as protein biology (structural and functional), human neuropathology, neurodegeneration, genetics/epigenetics, and any other discipline(s) considered necessary to address the center's proposed projects. Applicants are encouraged to consider including team members with expertise from outside of the traditional neurosciences, when appropriate to the research questions proposed. The inclusion of foreign investigators/sites is appropriate if justified.

In addition to the research projects, all applications must include an administrative core that will be responsible for overseeing the progress of all projects, convening regular teleconferences and in-person meetings, and working with NINDS program officials. The administrative core will also be responsible for developing a publicly-available library of all alpha-synuclein and amyloid-beta subspecies characterized by the center. As appropriate and consistent with achieving the goals of the program, the administrative core is expected to include a plan for sharing any unused LBD brain tissue and/or biospecimens that is collected by the center. Up to two additional cores (e.g., structural biology, neuropathology, etc.) may be proposed if justified to support methods and/or resources that are integral to the overall goal(s) of the LBD CWOW and that are required by multiple (at least two) CWOW projects. Applicants are encouraged to utilize existing resources for sharing purposes (e.g., the RCSB Protein Data Bank, the NIH NeuroBioBank, the PDBP, etc.) whenever possible.

Applicants to this program who are investigators on PD or AD related NIH-supported centers (e.g., Udall Centers, AD Centers, etc.) must include a letter from the relevant center director describing how the existing center and the proposed LBD CWOW are complementary and detailing what support (resources and budgetary) will be available to the LBD CWOW.

All projects should be supported by a timeline and yearly milestones for completion. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Achievement of milestones will be evaluated by NINDS, and funding of non-competing award years will depend on milestone accomplishment. Note that these awards will be managed as cooperative agreements; therefore, projects that do not comply with terms, conditions, and established milestones of the award and of this program may be terminated early.

Applicants are strongly encouraged to consult with the NINDS Scientific/Research contact when planning an application for further guidance on program scope, goals, and developing appropriate milestones.

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 from 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
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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 LBD CWOW director (PD/PI) must be an established leader in scientific research with a history of successful funding and proven expertise in the stewardship of large-scale research programs. CWOW directors must lead the Administrative Core and may lead no more than one other component (core or project). Other qualifying factors include current research productivity, active research funding (NIH R01-equivalent or greater) at time of submission, and capacity for visionary leadership of an interdisciplinary team.

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).

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

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 Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, 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:

Debra Babcock, PhD, MD
Telephone: 301-496-9964
Fax: 301-402-2060
Email: dbabcock@mail.nih.gov

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	6
Core	6
Project	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.

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Cores: optional, maximum of 2
• Projects: 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.

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 Resubmission applications, an Introduction to Application is required in the Overall component.

Specific Aims: Specific Aims should outline the overall vision and goals for the LBD CWOW. These Aims should be overarching and at a high level and distinct from the aims of the individual components and must address how neurotoxicity is induced by alpha-synuclein and beta-amyloid aggregates, and how these aggregates and their mechanisms of toxicity might interact with each other and/or contribute to selective vulnerabilities of cells and circuits.

Research Strategy: The research strategy should describe the methods, techniques, and analyses that the center will employ to achieve the vision laid out in the overall aims. Applicants should provide a general discussion of: 1) the significance of each individual project and how each contributes to the center's overall goal; 2) the need for any proposed cores and how they will interact with the projects and the Administrative core; 3) how each project and core synergizes, interacts, and supports each other; 4) the overall strategy of the Administrative core for managing the center and ensuring that all goals are completed in a timely fashion; 5) innovations in technique and methods that will contribute to accomplishing the research goals and advancing the field; and 6) how each site and each investigator is uniquely positioned to contribute world-class expertise and cutting-edge resources towards addressing the aims. If foreign components/institutions are participating, 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. Synergy must be evident among research projects and cores, such that successful completion of the aims could not be accomplished without the Center structure.

Letters of Support: Applicants must provide letters from the appropriate high-ranking institutional official(s) indicating the commitment of the institution to the LBD CWOW goals and specifying any institutional support or resources that will be made available to the LBD CWOW. Applicants who are investigators on related NIH-supported centers (e.g., Udall Centers, AD Centers, etc.) must include a letter from the relevant center director describing how the existing center and the proposed LBD CWOW are complementary, and detailing what support (resources and budgetary) will be available to the LBD CWOW. A letter of collaboration and support is required from any collaborating brain banks/tissue repositories.

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.

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

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

When preparing your application, 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.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• 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. The amount of effort for the core lead(s) must be commensurate with the requirements of the position and not less than two person months each. This level of effort is required whether or not salary is requested. Applicants may budget for costs associated with constructing the required protein library database and for regular CWOW meetings.

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 Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Describe the aims for ensuring that the overall vision of the proposed LBD CWOW is achieved. Hypothesis-driven research aims are not appropriate.

Research Strategy: The Administrative Core lead(s) (also the CWOW director(s)) should describe their research productivity, active research funding (NIH R01-equivalent or greater) at time of submission, and capacity for visionary leadership of an interdisciplinary team. Each application should detail a plan for supervising and coordinating the entire range of proposed activities. Applicants must explain the roles and responsibilities of Administrative Core personnel including scientific leadership, and administrative management and coordination of the proposed activities. Plans for holding regular meetings and facilitating communication between projects and cores; prioritizing core and resource usage/strategies; monitoring progress and ensuring that milestones are completed in a timely fashion must be clearly detailed. Furthermore, plans for ensuring that data/tissue/specimens collected by the center are shared in a timely fashion are also expected to be clearly detailed, as appropriate and consistent with achieving the goals of this program. An annual in-person center meeting is strongly encouraged. Clear and quantifiable milestones (e.g., for cross-site meetings and communications, establishing the protein structure library, etc.) creating go/no-go decision points for measuring the success of all this core's specific aims should be proposed.

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.

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Consistent with achieving the goals of the program, plans for developing a publicly-available library of all alpha-synuclein and amyloid-beta subspecies characterized by the CWOW are expected to be described. If new samples are being collected by project(s) or core(s), a sharing plan for unused tissues or specimens should be provided (transfer to established brain banks/repositories is strongly encouraged).

Appendix:

Limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core or Project Name)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Core.

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.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

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.
• 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 (Research Core)

Budget forms appropriate for the specific component will be included in the application package. The amount of effort for the PD(s)/PI(s) must be commensurate with the requirements of the position. This level of effort is required whether or not salary is requested.

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 Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims:  Describe the aims for providing the necessary resources and technical expertise to support the goals of the research projects and the overall LBD CWOW.  Hypothesis-driven research aims are not appropriate.

Research Strategy: Each application should detail the core service to be provided, including all equipment, methods, or services involved.  Provide a concise review of the relevant literature that justifies the need for the proposed core in supporting the research goals of the LBD CWOW. Describe all aspects of the core resource that are innovative, and any technical or methodological innovations that will be developed during the duration of the project.  Applicants should explain how this core will interact with other projects and/or cores within the LBD CWOW.  Cores must support at least two projects, and percent usage of core resources per project should be indicated.  If the core is providing or storing post-mortem brain tissue, criteria for assigning a neuropathological diagnosis should be described.   If the core is collecting or providing tissue or biospecimens, collection and storage protocols should be clearly described.  Clear and quantifiable annual milestones creating go/no-go decision points for measuring the success of all the core's specific aims should be proposed. 

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.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Research Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Project.

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.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

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.
• 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 (Research Project)

Budget forms appropriate for the specific component will be included in the application package. The amount of effort for the Research Project lead(s) must be commensurate with the requirements of the position. This level of effort is required whether or not salary is requested.

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 Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims:  List each specific hypothesis and objective of the proposed research project, briefly outline the methods proposed, and summarize the expected outcomes.

Research Strategy: Describe the research strategy for the project and how the research will advance knowledge about toxic subspecies of alpha-synuclein and amyloid-beta and their role in LBD pathology.  Provide a concise review of the relevant literature and its rigor, detail available pilot data, and justify the proposed aims and methods (applicants must discuss scientific premise, scientific rigor, and biological variables).  Provide alternative approaches to addressing the research aims if the proposed approaches fail.  Applicants should explain how this research project will interact and synergize with other projects and/or cores within the LBD CWOW.  Projects should focus on the use of human tissues and biospecimens; however, if the project proposes the use of non-human or immortalized cells/tissue, these must be strongly justified as critical to achieving the research goals.  If the project is using post-mortem brain tissue that is not provided by a CWOW core (e.g., from an external collaborator), criteria used to assign a neuropathological diagnosis should be described.  If the project is collecting or providing specimens, collection and storage protocols should be clearly described.  Clear and quantifiable annual milestones creating go/no-go decision points for measuring the success of all the project's specific aims should be proposed.  

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.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Research Project)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

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.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the CWOW 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 CWOW 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 CWOW that by its nature is not innovative may be essential to advance a field.

Does the CWOW 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 CWOW 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? Are the LBD CWOW aims, methods, and projects likely to shed light on the issues of how neurotoxicity is induced by alpha-synuclein and beta-amyloid aggregates and how these aggregates/mechanisms of toxicity might interact with each other and/or contribute to selective vulnerabilities of cells and circuits?  Is there evidence that each project/core contributes significant knowledge or resources towards the overall CWOW goal?  Does the CWOW structure provide opportunities for scientific advancement that would not be achieved by each project working alone? 

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the CWOW? If Early Stage Investigators or those 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? Is the LBD CWOW director (PD/PI) an established leader in scientific research with a history of research productivity, successful funding, and proven expertise in the stewardship of large-scale research programs?   Has he/she demonstrated a capacity for visionary leadership of an interdisciplinary team?  Is each investigator in the CWOW team an established leader with a history of innovative work in their area of research? 

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Does the application propose innovative use of human tissues/biospecimens in its approach to addressing its hypotheses?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the CWOW? 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 CWOW 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? Is the CWOW organized around an overall hypothesis for how neurotoxicity is induced by alpha-synuclein and beta-amyloid aggregates and how these aggregates/mechanisms of toxicity might interact with each other and/or contribute to selective vulnerabilities of cells and circuits?  Are the component parts of the CWOW (projects and cores) critical to achieving the goals of the CWOW in a timely fashion, and do they synergize with each other towards that end? Are the methods proposed appropriate for addressing the hypothesis, state-of-the-art and scientifically rigorous?

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? If the applicant is an investigator on related NIH-supported centers (e.g., Udall Centers, AD Centers, etc.) is a clear description provided as to how the existing center and the proposed LBD CWOW are complementary?  Does the application describe any support (resources and budgetary) from the existing center that will be made available to the LBD CWOW, and is this support appropriate?  Are letters of support provided from all external collaborators (e.g., external brain banks or tissue repositories?)

Reviewers will provide overall numeric scores; individual criterion scores are not provided.  The review criteria for the individual cores are provided below.

Administrative Core

Does the Administrative Core Lead/Center Director have appropriate expertise and dedicate sufficient time to administrative activities? If an Associate Director is named, does that person have required expertise to effectively assist the Center Director with scientific and administrative management?

Is there an appropriate plan for establishing and maintaining effective communications and cooperation among Center investigators on a regular basis?

Does the core provide a clear strategy for supervising and coordinating the entire range of proposed activities, including plans for monitoring progress and ensuring that component plans are implemented, accomplished, and all milestones are met?  Are plans included for prioritizing how core resources will be utilized?  Are there appropriate plans for management of data, specimens, and other resources?  Is the leadership approach, governance and organizational structure appropriate for the project?

Does the core provide clear and quantifiable milestones creating go/no-go decision points for measuring the success of its goals?   

Research Core(s)

Is the proposed core scientifically justified in the context of the CWOW's overall goal?  Are all equipment, methods, and/or services state-of-the-art, clearly described, appropriate for addressing the CWOW's hypotheses, and scientifically rigorous?  Are any technological or methodological innovations proposed?

Does the core Leader/Director have the appropriate expertise and dedicate sufficient time to core activities?

Does the core provide essential support, resources, and expertise to at least two of the research projects within the CWOW?

If the core is collecting or providing post-mortem brain tissue, are criteria for assigning a neuropathological diagnosis detailed and appropriate?  If the core is collecting or providing tissue or biospecimens, are collection and storage protocols clearly described and appropriate for preserving the specimens? 

Are clear and quantifiable milestones creating go/no-go decision points for measuring the success of all the core's aims provided?

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 CWOW project that by its nature is not innovative may be essential to advance a field or the overall goals of the CWOW. 

Significance

Do the project's aims/hypotheses address an important aspect of the CWOWs overall strategy for advancing knowledge about toxic subspecies of alpha-synuclein and amyloid-beta and their role in LBD pathology?  Is there a strong scientific premise for the project?  How will the project contribute to the success of other projects and to the overall success of the CWOW?  Is the project likely to result in major (rather than incremental) scientific advances?

Investigator(s)

Is the expertise of the research project leader, collaborators, and other researchers well suited to the project?  Is the research project leader an established scientist with a history of innovative work in their area of research?  Do all members of the project team dedicate sufficient effort to research activities?

Innovation

Does the research project utilize novel theoretical concepts, methods, or technologies?  Does the project propose innovative use of human tissues or biospecimens in its approach to addressing its hypotheses? 

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

Is there a clear description of how this research project will interact and synergize with other projects and/or cores within the LBD CWOW?

If the project is using post-mortem brain tissue that is not provided by a CWOW core (e.g., from an external collaborator), are criteria for assigning a neuropathological diagnosis detailed and appropriate?  If the project is collecting or providing tissues or biospecimens, are collection and storage protocols clearly described and appropriate for preserving the specimens? Does the project focus on the use of human brain tissue, human neuronal cells/slices/stem cells, and/or human blood/stem cells/CSF?  If the project proposes the use of non-human or immortalized cells/tissue, is this strongly justified as critical to achieving the research goals? 

Are clear and quantifiable annual milestones creating go/no-go decision points for measuring the success of all the project's specific aims proposed?

Environment

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

As applicable for the CWOW 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.

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 CWOW 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.

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

Not applicable

Not applicable

As applicable for the CWOW 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.

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

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 the 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 (NANDS) 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.

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.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 75and 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;
• Reporting to NINDS Program staff regarding timeline and milestone achievement during the course of the project, as delineated in the terms and conditions of award;
• Submitting an annual progress reports during the funding period, in a format as agreed upon by NINDS program staff;
• Accepting and implementing any other common guidelines and procedures developed for the LBD CWOW program;
• Timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement.
• Ensuring that a publicly-available library of all alpha-synuclein and amyloid-beta subspecies characterized by the center from post-mortem LBD brain tissue is developed, and that all unused LBD brain tissue and biospecimen are shared as appropriate and consistent with achieving the goals of the program.
• Awardees are expected to make new information and materials known to the research community not only investigator meetings but also in a timely manner through publications, web announcements, reports to NINDS program staff, and other mechanisms.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

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 the NINDS Project Scientists will be to facilitate and not to direct the activities. The NINDS Project Scientist will:

• 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;
• Participate in regular meetings with the LBD CWOW staff as described in the milestones.
• Coordinate the efforts of the awardee with other awardees under this FOA and those involved in related NINDS programs;
• Assist in promoting the availability of data and resources developed in the course of this project to the scientific community at large;
• In consultation with the NIH Program Official, 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 as appropriate).

An NIH Program Official will be responsible for the normal programmatic stewardship of the award and will be named in the award notice. The program official(s) will:

• Assist in enforcing general statutory, regulatory or administrative assistance policy requirements;
• Evaluate progress by reviews of technical or fiscal reports or by site visits to determine that performance is consistent with objectives, terms and conditions of the award;
• Ensure that activities proposed for development or implementation do not overlap or duplicate activities supported by other peer reviewed funding mechanisms;
• Assist with financial oversight of the LBD CWOW.

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

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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, and 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)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Debra Babcock, PhD, MD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: mailto:dbabcock@mail.nih.gov

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS) 
Telephone: 301-496-9223
Email: nindsreview.nih.gov@mail.nih.gov

Tijuanna DeCoster, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: mailto:decostert@mail.nih.gov

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.