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

The HIV life cycle comprises a progression of assembly and disassembly of multiple macromolecular complexes with components of both the virus and the host cell. From the interplay of viral proteins among themselves and with the cellular machinery, to the activity of viral enzymes and the appropriation of host factors to achieve infection, such complexes are the fundamental effectors of viral reproduction and proliferation. These complexes range from binary protein-protein and protein-nucleic acid complexes to much larger multicomponent complexes. The complexes offer the potential to provide interventional strategies for the prevention, treatment, and cure of HIV infection.

Although the first step towards the exploitation of these targets, the determination of their high-resolution structures, has been accomplished in many instances, more remains to be done, including the identification and characterization of interactions with additional host factors, interactions with viral or cellular membranes, and binding of therapeutics to viral and/or virus-host complexes. Toward this goal, NIGMS funded the Centers for HIV/AIDS-Related Structural Biology (P50) program with co-funding by NIAID from 2007 until its transfer to NIAID in 2019. NIAID intends to continue the support of a Centers program with this Funding Opportunity Announcement (FOA). The goal of the initiative is to support teams of scientists in relevant fields to use cutting-edge technologies to address complex questions related to HIV structural biology and viral dynamics across a broad range of resolution scales. To be successful, funded Centers are expected to collaborate and must reach out to the biological community doing research aimed at identifying and validating the role of macromolecular complexes in HIV infection, including sharing of data by timely submission of structural information to appropriate databases.

The purpose of this FOA is to support dynamic, multidisciplinary consortia of structural biologists, virologists, and computational scientists to resolve complex biological structures relevant to HIV prevention, treatment, and cure. The consortia are expected to leverage common resources, facilitate new collaborations, and engage and support the next generation of HIV structural biology researchers.

The goal of the Centers for HIV Structural Biology program will be to support teams of scientists to develop and utilize cutting edge technologies and methodologies to address the most challenging scientific questions involving the structures and functions of HIV-related macromolecular complexes. Centers are expected to move beyond the determination of static structures and into an understanding of the dynamics of complexes with an eye toward informing mechanistically based discovery and/or design of interventions for the prevention, treatment, and cure of HIV. The development of specific interventions is not the purpose of the FOA; rather, the goal is to establish new technologies and methodologies to facilitate the discovery of new therapeutic targets, elucidate the mechanisms of action of interventions, or determine the structural basis for interventional failures.

Special emphasis should be placed upon those known components of the virus and/or host for which a sufficiently complete structure has yet to be determined. Restriction factors and viral proteins that counteract their function remain of interest, as well as newly recognized factors that contribute to the establishment or maintenance of viral latency, which may represent potential therapeutic targets to effect a cure. With this FOA an emphasis is placed on current poorly characterized categories of complexes that are critical to the virus life cycle, including RNA, RNA/protein, DNA/protein, and protein/membrane interactions. For all the above molecules and complexes, integration of structure with validation strategies, including virological, biochemical, and computational, is essential to understanding their biological functions. The research being proposed is expected to push the boundaries of what is feasible. As such, it is recognized that aspects of the Research Plan will necessarily be of high risk.

Unlike previous iterations of this Centers program, each Center should not have just one, centralized scientific theme in which it specializes. Rather, for this FOA, each Center should be built around three to four diverse scientific projects in which innovative technological approaches will be applied to solve distinct scientific questions that address knowledge gaps of significance to one or more NIAID research priorities related to HIV prevention, treatment, or cure. The research plans will need to be dynamic and adaptable to evolve as new data become available. Importantly, the scientific areas of specialization need not be directly related to one another; rather, they should leverage the best talents and technologies of the team to address the most challenging, compelling, and pertinent scientific problems related to HIV prevention, treatment, and cure.

• Each Center must have demonstrated capabilities for the determination of high-resolution structures of macromolecular complexes.
• Centers must be engaged in basic and applied research supporting NIAID priorities of HIV prevention, treatment, and cure.
• Centers may include all aspects of structural biology related to HIV, including structural determination, dynamics and functional characterization of macromolecular complexes among and between components of HIV, the host cell, the immune system, and therapeutic, preventative, or curative interventions.
• Centers are encouraged to explore higher-order structures across a broad range of resolution scales, including subcellular, cellular and tissue organization in order to add context to molecular structures and their functional characterization.
• Centers are strongly encouraged to have a technology component designed to push the state-of-the-art in structural determination and dynamic characterization of HIV and/or host complexes. For example, technologies such as protein design, dynamic modeling, or hybrid imaging methods should be employed to remain on the cutting edge of new discoveries.
• Demonstration of substantial institutional support for appropriate equipment and other resources available to the investigators is desirable.
• Clinical research involving human tissues, cells and fluids is encouraged.
• Animal research using appropriate models is allowed.

Non-Responsive Areas of Research 

• Applications focused on any of the following will be deemed non-responsive and will not be reviewed:
• Applications that propose clinical trials.
• Applications that do not include structural determination at atomic resolution.
• Applications that do not identify specific areas of scientific specialization.
• Applications that are focused primarily on therapeutic development without a major focus on basic science research.
• Applications that are focused exclusively on determinants of drug resistance.

Structure Determination 

Although X-ray crystallography or cryo-electron microscopy may be the method of choice in many instances, additional methods such as nuclear magnetic resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS) and other approaches may offer particular advantages for the characterization of certain components such as RNA or large multicomponent complexes. Similarly, methods such as single molecule F rster resonance energy transfer (smFRET), mass spectrometry and others may also play important roles. Given the scope of the research to be undertaken, each Center must have available a range of structure determination methods, from routine to more advanced, that can be brought to bear on the complex scientific questions being addressed. It is expected that methods unique to a Center will be made available to other Centers on a collaborative basis.

Technology Advancement 

Each Center is required to have a technology effort designed to advance the state-of-the-art in structure determination and dynamics. Characterization of macromolecular complexes (particularly when such complexes include nucleic acids, carbohydrates or lipids) should push the limits of the current state of the art, both in terms of the technologies needed for structure determination and the biology needed to produce sufficient material for analysis. Centers should also incorporate combinations of cutting-edge technologies and methodology for biological characterization and validation of structures of macromolecular complexes.

Methods that characterize the dynamics of relevant complexes may provide a more realistic picture of biological function than static structures and potentially more relevant information for development of therapeutics targeted to those functions. Efforts to characterize the dynamics of virus or virus/host complexes may, for example, include single-molecule and correlative electron microscopy methods as well as dynamic modeling approaches, which are being used increasingly to examine biological processes in vivo. Collaboration with scientists with demonstrated expertise in these methods is strongly recommended.

Collaboration 

Each Center must actively seek collaborations with outside investigators to address gaps in expertise. The set of possible targets for structure determination is very large. Thus, it is unreasonable to expect the Centers, even when considered together, to possess the expertise to explore and develop all such targets. Therefore, it is essential that each Center have a mechanism and infrastructure for establishing and maintaining collaborations with outside researchers. These collaborators should be able to enter the structure determination pipeline at several points, from the identification of biologic targets to the provision of purified macromolecular complexes and subsequent structural and functional analyses. The goal is to mesh structural and functional studies of these interactions such that they inform and build on each other. Thus, it is expected that potential competitors will collaborate to the benefit of the projects as a whole.

NIAID encourages collaborations and formal interactions that leverage existing research infrastructure, including the Centers for AIDS Research (CFAR), the Consortia for HIV/AIDS Vaccine Development (CHAVD) and Martin Delaney Collaboratories for HIV Cure Research (MDC). Centers are additionally encouraged to collaborate with government researchers, including those at the NCI HIV Dynamics and Replication Program, NIAID Vaccine Research Center, US Military HIV Research Program, or any other investigator with the skills and interest to contribute in a substantial fashion to the goals of the Center.

 The overall structure of the Center is designed to support multidisciplinary, multi-institutional consortia of HIV/AIDS researchers in the conduct of their Research Projects. As described below, Centers will include an Administrative Core to manage overall Center activities, a Developmental Core to foster early career investigators both inside and outside the Center membership, Scientific Cores to support the research goals of the Center, and three to four Research Projects. An External Advisory Committee (EAC) will oversee the management and oversight of the overall Centers Program.

 Administrative Core 

The Administrative Core will be responsible for managing, coordinating, and overseeing the entire range of Center activities, monitoring progress, and ensuring that the project milestones are being met and implemented effectively within the proposed timelines. The Administrative Core must provide both an organizational and administrative structure that is conducive for ensuring collaborative efforts and interaction among the Projects and Cores. Additionally, the Core should coordinate and facilitate communication with other collaborating partners. 

Executive Committee (EC). Each Center will include an EC and Scientific Advisory Board (SAB). The EC is an internal committee that will serve as the governing body of the Center, assisting the PD/PI(s) in setting the direction of scientific activities based on ongoing evaluations of research priorities and opportunities. The EC should put in place policies and procedures to support operations and scientific progress, including the reallocation of funds, development of needed working groups, engagement of new collaborators and/or technologies relevant to the evolving scientific priorities, and establishment of guidelines for presentation and publication of the results of collaborative projects. The EC will be comprised of 3-5 voting members, chaired by the PD/PI(s), and should include 2-4 key personnel representing leadership of the Center research projects.

Scientific Advisory Board (SAB). The SAB will be an independent, external advisory body that acts as a resource for the Principal Investigator and the Executive Committee, but it will not be involved in the day-to-day activities of the Center. The SAB will include at least 3 active members not affiliated with the applicant institution(s) or other institutions receiving funds from the award. The SAB will assist in review of research productivity, progress toward the proposed goals, adherence to timelines, and the continued relevance of the research approach. The SAB may recommend new scientific directions or re-prioritization of research as appropriate. Members of the SAB will be appointed by the EC in consultation with and subject to the approval of the NIAID Project Scientist. The SAB should meet at least once a year and give advice directly to the Center. The NIAID Project Scientist may attend each meeting of the SAB as an observer. Candidates for the SAB should not be named in the application or solicited prior to award. 

Centers will also establish outreach and data sharing/dissemination mechanism(s) for the scientific community to have timely access to all data generated in the Center. Each Center is expected to host a publicly accessible website devoted to Center activities. The website may also include investigator accessible, non-public resources for sharing of confidential information.

 Developmental Core 

In accordance with the NIAID mission to foster the next generation of scientists, each Center must include a Developmental Core. The Developmental Core will provide educational and mentoring activities for students, postdoctoral fellows, and early career investigators associated with the Center. Such activities may include seminars, journal clubs, short courses, individualized instruction on specific technologies or methodologies, temporary placement in a collaborator’s laboratory, individualized mentoring on specific areas of scientific research or grant writing, and mock study sections. Small pilot awards may also be provided to early career investigators within the Center to promote their path to independence. Additionally, the Developmental Core may support activities such as hands-on workshops, grant development committees, or funds for individuals to attain specific research skills not available in the Center. In accordance with the NIAID mission to foster the scientific careers of those from diverse backgrounds, each Center will endeavor to maintain an open and inclusive environment for these activities.

The Developmental core will also administer a Collaborative Development Award (CDA) program to fund specific pilot research projects aligned with the goals of the Center. The purpose of Collaborative Development Awards will be to support early career HIV investigators and investigators new to the HIV research field who are not associated with the Center. These projects may encompass research to obtain preliminary data for an R01 application, perform feasibility studies, support new and emerging science in HIV research, and facilitate new collaborations among faculty or institutions in diverse areas of science in support of high priority HIV research. 

 Scientific Cores 

Where appropriate, up to four Scientific Cores will support specific technologies or methodologies associated with the proposed Center efforts.  Scientific Cores should provide services and/or facilities vital to the efforts of two or more Projects.  Such services may include protein production and purification, X-ray crystallography, microscopy, etc. Scientific Cores should be devoted to the goals of the Center as a whole and should interact with and support one another.

 Research Projects

Centers are anticipated to be organized primarily around three to four diverse, scientifically distinct Research Projects that will perform studies directed towards the overall Center goals. Where multiple and/or complementary expertise is required, project investigators and other collaborators will work in concert to overcome obstacles to achieve the Center aims.

Management and Oversight 

External Advisory Committee (EAC): The EAC is an external advisory body that will review progress of the overall Centers program and share recommendations for maximizing productivity and collaboration across the program with Center PD(s)/PI(s) as part of an NIAID-sponsored annual scientific meeting. Additional evaluation criteria will include the Center’s ability to produce and share data with the larger scientific community, coordinate research efforts within the Center, and foster early career investigators. For each Center, the EAC will make recommendations regarding the continuation or re-direction of the research program(s) and assess each Center’s progress in the areas of collaboration and coordination with the other Centers. Program staff will work with Center PD(s)/PI(s) to appoint an EAC comprised of experts in the field who are not directly affiliated with any of the Centers.

 Potential members of the EAC should not be named in the application or solicited prior to award.

To ensure coordination and cooperation among the funded Centers and the other members of the scientific research community working in areas germane to the mission of the Centers, an annual scientific meeting will be held. Attendance of the principal investigator and key investigators from each Center is expected. Attendance of key collaborating investigators is also highly encouraged. The collaborative aspects of the overall program are essential for its success. Given the dynamic nature of collaborations, this aspect is expected to change from year to year. Therefore, each Center must update its plans for collaboration annually. In the event that additional funds become available, support could be provided for innovative approaches that are conceived after the onset of the Center grant. 

All data are expected to be made available to the public in a timely manner. All coordinates and structure factors, NMR resonance assignments and restraints resulting from research supported by funds from this FOA, whether the project originated in the Center or in the laboratory of a development award recipient or a collaborator, are expected to be available from the Protein Data Bank or BioMagResBank on publication. Similarly, structures of complexes solved by electron microscopy are expected to be submitted to an appropriate publicly accessible resource such as the Electron Microscopy Data Bank (EMDB) at the Protein Data Bank in Europe.

Applicants are encouraged to leverage other resources and develop creative collaborations where possible to support the overall goals of the Center. Institutional support is highly encouraged.

Applicants are encouraged to contact the Scientific/Research Contacts to discuss their application and arrange a pre-application meeting prior to submission of their application.

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:

o   Hispanic-serving Institutions

o   Historically Black Colleges and Universities (HBCUs)

o   Tribally Controlled Colleges and Universities (TCCUs)

o   Alaska Native and Native Hawaiian Serving Institutions

o   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) 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) 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.
• o   NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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).

 

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST 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.

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.

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:

Robert Unfer, Ph.D.
Telephone: 301-301-641-1981
Email: robert.unfer@nih.gov

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	6
Core (Use for Developmental and Scientific Cores)	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.

The application should consist of the following components:

• Overall: required
• Administrative Core: required, maximum of one
• Developmental Core: required, maximum of one
• Scientific Cores: optional, maximum of four
• Research Projects: required, minimum of three, maximum of four

When preparing your application, 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.

Research & Related Other Project Information (Overall)

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.

Specific Aims: Provide the specific aims for the entire Center.

Research Strategy: Describe how the projects will contribute to the overall aims of the Center. Include a discussion of the contribution of the cores to these efforts.  Discuss the technology development focus for the Center.  Describe the problem(s) or barrier(s) the technological advances will solve or overcome and the advantages over existing technology. Place the proposed technology studies in the context of the field and the Center.  Describe how all the projects and cores will contribute in a concerted manner toward the Center’s goals.  Provide a comprehensive overview of how Center components will coordinate their efforts with collaborators, both supported by developmental awards and outside the Center. Applicants should describe:

• The specific scientific problems to be solved
• Combinations of innovative approaches and technologies to be developed and applied
• Identification of potential bottlenecks and alternative approaches
• The commitment and expertise of the investigators and how their areas of specialization complement one another with respect to the scientific questions to be addressed
• A clear and detailed management plan along with milestones for guiding decisions as the Center’s projects evolve and adapt to the changing scientific landscape
• A plan for outreach and collaboration with the wider HIV research community
• Strategies for recruiting, mentoring, and educating the next generation of HIV structural biologists

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 data are expected to be made available to the public in a timely manner. All coordinates and structure factors, NMR resonance assignments and restraints resulting from research supported by funds from this FOA, whether the project originated in the Center or in the laboratory of a development award recipient or a collaborator, are expected to be available from the Protein Data Bank or BioMagResBank on publication. Similarly, structures of complexes solved by electron microscopy are expected to be submitted to an appropriate publicly accessible resource such as the Electron Microscopy Data Bank (EMDB) at the Protein Data Bank in Europe.

Appendix:

Only 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 human subjects research, clinical research, and/or NIH-defined 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

PHS Assignment Request Form (Overall)

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.

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.

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

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

A minimal effort level of 1.5 person-months is required for the contact PDs/PIs for multi-PI applications and 3 person-months for single PI applications.

Within the appropriate budget sections, include funds for the following items in support of the research program:

• Administrative staffing roles with expertise in the following areas: day-to-day operation, organization, communication, and coordination of Center activities, including webinars, teleconferences, Executive Committee (EC) and Scientific Advisory Board (SAB) meetings, and to track and record metrics of productivity, including Center membership, affiliations, and positions; publications; and meeting abstracts.
• Expenses for communication among Center investigators and partners and for outreach to outside researchers and community members via establishment and maintenance of a Center website.
• Travel and other expenses related to hosting an annual Center SAB meeting in Bethesda, MD for Center evaluation and strategic planning activities. Travel expenses for SAB members should be included.
• Travel expenses for PD/PI(s), key investigators and/or administrative staff to participate in an annual NIAID-sponsored meeting to facilitate interactions and communication among the Centers.

The budget justification should include a breakdown of the apportionment of funds for each of the proposed Research Projects, Cores, and Operations and Management activities for the first year. The budgets for out-years should represent best estimates for the general research plan. Resource allocations are expected to change over time from what is initially proposed.

In the budget justification section, applicants may include any in-kind support the Center receives such as operating budgets provided by the institution, large gifts, dedicated space, direct support of Center personnel, and dedicated equipment, including support for research infrastructure-related functions such as directing or managing the Center, and similar activities. Such support should be labeled in-kind in the justification section.

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 (Administrative Core)

Specific Aims: Briefly outline the goals for the Administrative Core.

Research Strategy: Detail the management plan for the entire Center and its collaborations with other Centers and the HIV research community at large. Describe the policies and procedures for the Center, including how decisions are made, mechanisms for conflict resolution, frequency of internal progress reporting, and how the overall Center progress will be assessed, including the annual strategic planning process and process for reallocating funds within the Center as needed.

Describe any formal collaborations with researchers who are funded by alternative sources, such as NIH-funded Centers, Collaboratories and intramural laboratories, and how those collaborations will further the Center scientific goals.

Describe any additional resources that the Center will access, including institutional financial support, industry partners or other independent sources of Center support.

Describe also the mechanisms and infrastructure that will be used to establish and maintain collaborations with the scientific community, beyond the Collaborative Development Program, that is engaged in the identification, validation and study of HIV/host complexes. This section should document existing collaborations. Describe also the intended composition and activities for the Center Scientific Advisory Board. Do not name or solicit advisory board candidates prior to award.

Include a description of the activities the Center will provide such as seminars, meetings and workshops that cover the areas of focus and technologies for the Center and HIV structural biology in general. Include a description of online resources planned for the Center, including member restricted and publicly accessible webpages for information sharing and Center meeting activities. Outline plans to enhance the diversity of the biomedical workforce (NOT-OD-20-031); each center should endeavor to maintain an open and inclusive environment for these activities.

Letters of Support: In addition to any letters of support, provide letters from each non-member investigator who will be collaborating with the Center. Letters should discuss the collaborator’s commitment and scientific contributions to the Center efforts and its goals.

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 data are expected to be made available to the public in a timely manner. All coordinates and structure factors, NMR resonance assignments and restraints resulting from research supported by funds from this FOA, whether the project originated in the Center or in the laboratory of a development award recipient or a collaborator, are expected to be available from the Protein Data Bank or BioMagResBank on publication. Similarly, structures of complexes solved by electron microscopy are expected to be submitted to an appropriate publicly accessible resource such as the Electron Microscopy Data Bank (EMDB) at the Protein Data Bank in Europe.

Appendix:

Only 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.

When involving human subjects research, clinical research, and/or NIH-defined 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

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

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.

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 Developmental Core budget should include all expenses necessary to support Center development activities. The budget may include estimates for the number and costs for internal pilot awards that will be made to support early career investigator transition to independence. All items should be fully justified for allocation of Center funds within the Budget Justification. Any budget requested for support of the Developmental Core Director must match the effort associated with the Developmental Core work conducted.

Collaborative Development Awards

Applicants should budget funds to support Collaborative Development Awards to support pilot research projects that stimulate interest in HIV/AIDS research. Approximately 10% of the direct costs of the award (excluding consortium F&A costs) should be expended on this award program annually. These funds may be used by early career investigators in the HIV/AIDS field to support research towards independent funding. Funds may also be used for investigators not in the HIV/AIDS research field to encourage them to explore novel approaches to HIV/AIDS research questions. Applicants may request support for investigator salary for Collaborative Development Awards. Collaborative Development Awards must be approved by the NIAID Project Scientist prior to the distribution of funds. Senior investigators in the HIV/AIDS research field are not eligible for Collaborative Development Awards except in rare circumstances with approval from the NIAID Project Scientist. The Collaborative Development Award budget should be included in Other Expenses and listed as "Collaborative Development Award." A budget justification is required for these costs, including an estimate for the number of projects per year.

Applicants may include travel funds to support early career faculty to attend scientific meetings to present the results from their Collaborative Development Awards. Center funds cannot be used to provide travel scholarships for investigators without a Collaborative Development Award.

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.

Specific Aims: Describe the specific aims of the Developmental Core and how the Core will enhance, increase, improve or stimulate the HIV/AIDS research in the Center and how it will support the next generation of HIV/AIDS researchers both within the Center and for the HIV/AIDS research community as a whole.

Research Strategy: Describe the role of the Developmental Core in the Center and how the responsibilities of this Core advance the goals of the Center. Describe the plans to support early career investigators in HIV/AIDS research and the activities undertaken by the Core to enhance their ability to secure independent funding for their research, including plans for how pilot awards will be made to early career investigators. Include plans for mentoring early career investigators, including investigators who are not successful in obtaining developmental project funding. Outline any additional activities supported by the Core to facilitate the transition to independence for early career investigators.

Describe the process used by the Developmental Core for prioritizing opportunities for funding and the scope of the HIV/AIDS science to be supported. Explain how Collaborative Development Awards will be solicited, reviewed, awarded, administered, and evaluated for progress and outcomes. Provide a plan for use of first year developmental funds, including a list of potential topics for developmental projects. Describe the policies and procedures for the proposed Developmental Core, including for example, how decisions are made, frequency of internal progress reporting, and how the overall Core progress will be assessed, including the strategic planning process, and process for reallocating funds within the Core as needed.

Describe how the Developmental Core will monitor and ensure compliance of all developmental projects involving human or animal subjects, and obtain the appropriate approvals (i.e., annual IRB approvals, FWA, IACUC, human subjects research training, etc. in domestic and foreign institutions). Describe procedures for obtaining assessments from HIV/AIDS investigators about the Core’s ability to meet research needs.

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 data are expected to be made available to the public in a timely manner. All coordinates and structure factors, NMR resonance assignments and restraints resulting from research supported by funds from this FOA, whether the project originated in the Center or in the laboratory of a development award recipient or a collaborator, are expected to be available from the Protein Data Bank or BioMagResBank on publication. Similarly, structures of complexes solved by electron microscopy are expected to be submitted to an appropriate publicly accessible resource such as the Electron Microscopy Data Bank (EMDB) at the Protein Data Bank in Europe.

Appendix:

Only 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.

When involving human subjects research, clinical research, and/or NIH-defined 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

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

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.

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.

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.

Specific Aims: Describe the aims of the core in the context of the overall goals of the Center.

Research Strategy: Detail the function of the Scientific Core in the furtherance of its aims and of the overall goals of the Center. Describe in detail the facilities and/or services to be provided. Detail the Core s integration into the Center and how the other components will intersect with and/or contribute to their respective efforts. If applicable, briefly describe how this Core will coordinate with collaborators, developmental awardees and other researchers outside of the Center. Describe procedures for obtaining assessments from Center investigators about the Core’s ability to meet research needs.

Letters of Support: Provide only if necessary to document access to a shared resource or sample repository.

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 data are expected to be made available to the public in a timely manner. All coordinates and structure factors, NMR resonance assignments and restraints resulting from research supported by funds from this FOA, whether the project originated in the Center or in the laboratory of a development award recipient or a collaborator, are expected to be available from the Protein Data Bank or BioMagResBank on publication. Similarly, structures of complexes solved by electron microscopy are expected to be submitted to an appropriate publicly accessible resource such as the Electron Microscopy Data Bank (EMDB) at the Protein Data Bank in Europe.

Appendix:

Only 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.

When involving human subjects research, clinical research, and/or NIH-defined 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

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

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.

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.

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

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.

Specific Aims: Describe the aims of the Research Project in the context of the overall goals of the Center.

Research Strategy: Detail the approach to be taken to advance knowledge on the Center goals. Discuss also the technology development, if applicable, for the Research Project. For both Center goals and technology development, include milestones and a discussion of the likely major bottlenecks to be encountered. Alternative approaches should be described in sufficient detail to give reasonable confidence that bottlenecks can be overcome. Include a description of any unpublished preliminary results and/or cite relevant key publications. Detail the Project s integration into the Center and how the other components will intersect with and/or contribute to their respective efforts. If applicable, briefly describe how this Project will coordinate with collaborators, both supported by developmental awards and outside the Center.

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 data are expected to be made available to the public in a timely manner. All coordinates and structure factors, NMR resonance assignments and restraints resulting from research supported by funds from this FOA, whether the project originated in the Center or in the laboratory of a development award recipient or a collaborator, are expected to be available from the Protein Data Bank or BioMagResBank on publication. Similarly, structures of complexes solved by electron microscopy are expected to be submitted to an appropriate publicly accessible resource such as the Electron Microscopy Data Bank (EMDB) at the Protein Data Bank in Europe.

Appendix:

Only 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.

When involving human subjects research, clinical research, and/or NIH-defined 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

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

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

Important reminders:

All PD(s)/PI(s) 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.

 

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. Applications submitted to the NIH in support of the NIH mission 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 Center to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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 project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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?

Specific to this FOA: Is the overall Scientific Agenda compelling, with clear rationale for the proposed projects and cores? Are the plans under each of the projects scientifically meritorious? Do projects and cores support structural determination of high-complexity, difficult to solve problems?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? 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?

Specific to this FOA: Do(es) the PD(s)/PI(s) have documented leadership and management experience with large, complex, multidisciplinary research collaborations? Are the members of the Center Executive Committee likely to be able to effectively manage changes in research priorities and resource allocation?

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?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: Are the proposed approaches coherent and focused on important aspects of HIV structural biology? Will the overall Center strategy adequately address important roadblocks to structural determination of relevant HIV and host factor complexes?

Is the value of supporting the proposed research projects together significantly greater than what could be achieved through support of each separately?

Are there appropriate plans and mechanisms for budgetary reallocation and shifting research priorities? Are there appropriate and feasible decision-making processes for incorporating new research activities in response to emerging opportunities and eliminating unproductive research projects to maintain innovation as the science evolves?

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?

Specific to this FOA: Has the applicant adequately described plans to leverage existing Government funded resources and provided documentation that these resources will be available to the Center investigators? Is there adequate support to manage complex funding of sub-projects across multiple institutions? Is additional institutional support provided and are other funding sources leveraged to create added value and further synergy within the Center structure?

Reviewers will consider the review criteria below in the determination of scientific merit and provide an overall impact score (a single numerical score) for each Core (i.e., Administrative, Developmental, and Scientific) and Research Project.

Does the annual strategic planning process adequately describe the scientific and management plans? Are the policies and procedures appropriate for evaluating Cores and projects, for reassigning priorities and for developing and utilizing outcome measurements? Is a plan to prioritize, allocate and manage fiscal resources adequate? Has the applicant provided sufficient detail regarding how the Center will be evaluated and remediation strategies if progress is poor? Are the plans for outreach and collaboration likely to have a significant effect on the field at large?

How well does the Developmental Core address the need for multi-disciplinary research within the HIV structural biology field? Are the Collaborative Development and pilot award programs structured to augment the goals of the Center? Is the plan to solicit, review, award, administer and evaluate pilot and collaborative developmental awards adequate? Has the applicant provided a plan for attracting early career and non-HIV/AIDS investigators into the Center? Are the plans for mentoring early career investigators adequate?

Will the Scientific Core or Research Project have the ability to support the research base, enhance research collaborations, and produce an economy of scale? Is the Scientific Core or Research Project staffed appropriately to address the workload?  Does the Scientific Core or Research Project have plans for prioritization of projects, services and allocation of resources?

Are the Scientific Core or Research Project Director(s), collaborators, and other researchers well suited to the Scientific Core or Research Project? If directors are 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 Scientific Core or Research Project is collaborative or multi-PD/PI do the investigators have complementary and integrated expertise; is their leadership approach, governance and organizational structure appropriate for the Scientific Core or Research Project? Does the proposed Scientific Core or Research Project leadership have appropriate qualifications to achieve success of the Scientific Core or Research Project?

Are the concepts, approaches, methodologies and/or instrumentation novel?  Is a refinement, improvement, or new application of theoretical concepts, approaches, methodologies and/or instrumentation proposed?  Does the Scientific Core or Research Project challenge and seek to shift current research? 

Are potential problems, alternative strategies, and benchmarks for success presented? If the Scientific Core or Research 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 Scientific Core or Research Project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Is the institutional support provided appropriate for the Scientific Core or Research Project? Are the equipment and other physical resources available to the investigators adequate for the core proposed? Will the Scientific Core or Research Project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Is there adequate institutional commitment, including space, financial support and other resources for Scientific Core or Research Project activities?

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

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

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

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

Not Applicable

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

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 the National Institute of Allergy and Infectious Diseases 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 Allergy and Infectious Diseases 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 recipient’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.

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

Awardee-selected projects that involve clinical studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. 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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex.  This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides 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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. 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 https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
• 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.
• HHS funded health and education programs must be administered in an environment free of sexual harassment.  Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws.  Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions.  Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.  

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. 

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 Parts 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 program, 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:

• Planning, directing, and executing the proposed research in accordance with the proposed timeline
• Establishing the membership and responsibilities of the EC within three months of the award
• Communication with the NIAID Project Scientist regarding the status of ongoing research, changes in personnel, changes in research plans, etc.
• Establishment of a Center website
• Timely acquisition of any proprietary rights, including intellectual property rights, and all materials appropriate for performing the project(s)
• As part of the annual progress report, provide a summary outlining interaction among the group members and with the NIAID Project Scientist; and a complete, cumulative list of all publications attributable to the award
• Timely presentation/publication of work supported in part or whole by this Cooperative Agreement; prior notification of the NIAID Project Scientist regarding any major presentations or publications and appropriate acknowledgement of NIH support
• Holding an annual SAB meeting to review progress, plan and design research activities, and establish priorities, to include the membership of the EC, key personnel, and NIH Program representatives
• Integrating and implementing the recommendations of the SAB into the activities of the Center.

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

• Participation in the review and approval of changes in research activities and resource allocation
• Facilitating access to resources and information that otherwise might not be available to the awardee
• Advising on the management and technical performance of the program, and coordinating with other appropriate NIH staff to provide advice or assistance to the awardee on specific scientific, technical or management issues
• Facilitating interactions between the awardee and other groups of importance to the awardee, for example, NIAID Clinical Trial Networks, pharmaceutical and/or biotechnology companies, or community stakeholders
• Providing guidance and oversight on compliance with Federal regulations related to human subjects research and IC policy on clinical research
• Participation in the kick-off meeting, annual SAB meeting, webinars, teleconferences, and other meetings as appropriate, to review research progress and direction and to provide guidance
• The NIAID Project Scientist may participate in the activities of the External Advisory Committee as a non-voting member
• The role of NIAID will be to facilitate and not direct the activities. It is anticipated that decisions on all activities will be reached by consensus or EC majority vote and that appropriate NIAID Program staff will be given the opportunity to offer input as non-voting members. The NIAID Project Scientist will not participate as a co-author on any publications resulting from the research.
• Additionally, an agency program official or IC 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:

• The PD(s)/PI(S) and the NIAID Project Scientist will collaborate in the establishment of the Scientific Advisory Board by providing input and approval on the proposed membership and determining the roles and responsibilities of the SAB.

Dispute Resolution Process

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 Executive 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. 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 regulations 42 CFR Part 50, Subpart D and HHS regulations 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 submission by the due date, 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 instructions, 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

David McDonald, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-7815
Email: david.mcdonald@nih.gov

Robert Unfer, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-641-1981
Email: robert.unfer@nih.gov

Nicole Guidetti
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-6934
Email: Nicole.Guidetti@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.