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

Required Application Instructions

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

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The National Institute of General Medical Sciences invites applications for Centers that will support the structural determination and functional characterization of macromolecular complexes among and between components of the human immunodeficiency virus (HIV) and the components of host cells.

As for any virus, the life-cycle of HIV is comprised of a progression of assembly and disassembly of multiple macromolecular complexes among 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 usurpation of host factors to achieve replication, 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, often including carbohydrates and lipids (membranes). These complexes offer the potential to provide intervention strategies for the treatment and prevention of AIDS. Although the first step towards the exploitation of these targets, the determination of their high resolution structures, has been accomplished for some complexes, much remains to be done, including the identification and characterization of additional host factors. Thus the goal of this Funding Opportunity Announcement (FOA) is the continuation and/or creation of Centers dedicated to the high resolution structural and functional/dynamic characterization of these complexes. While the purpose of this FOA is not to directly fund specific drug development, the establishment of new technologies/methodologies to advance drug design is desirable. Methods and studies that could elucidate the structural basis for anti-viral resistance are also desirable. In order to succeed, these Centers must collaborate among themselves and are strongly encouraged to reach out to the biological community doing similar research, including sharing of data by timely submission of structural information to appropriate databases.

Protein/protein complexes, both among the viral proteins, as in the structures of the virion, and between viral and host proteins, have been the focus of most prior efforts. This should continue, although a greater emphasis should be placed upon components of the virus and/or host for which a sufficiently complete structure has yet to be determined, rather than for single proteins such as reverse transcriptase and protease for which a wealth of detailed information is already available. Restriction factor targets are of particular interest, especially factors that contribute to the establishment or maintenance of viral latency and thus may represent potential therapeutic targets to effect a cure. With this re-issued FOA we would once again strongly encourage investigation into poorly characterized categories of complexes, including RNA, nucleic acid/protein, and protein/membrane interactions. For all the potential molecules and complexes integration of structure with validation strategies, including computational, biochemical, and systems biology/interactome analyses, is essential to understanding their biological functions.

The goal of this announcement is to attract the best scientists in relevant fields to attack the problem of characterizing HIV-related macromolecular complexes. Hence the application should focus on

the specific problems to be solved:

• approaches to be used
• identification of potential bottlenecks
• a plan for outreach and collaboration to the wider HIV biology community
• a workable management plan along with milestones
• the commitment and past experience of the investigators.

The research being proposed is expected to push the boundaries of what is feasible. As such, it is recognized that aspects of the plan necessarily will be of high risk.

Structure Determination

Each Center must have demonstrated capabilities for the determination of high-resolution structures of macromolecular complexes. Although X-ray crystallography may remain the method of choice in many instances, alternative approaches such as NMR and cryo-electron microscopy offer particular advantages for the characterization of certain components such as RNA or for larger multicomponent complexes. Similarly, small angle x-ray scattering, single molecule FRET, mass spectrometry and other methods also may 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. It is expected that methods unique to a Center will be made available to other Centers on a collaborative basis.

Biological Theme

Each Center must have a focus of investigation within the broader biology of HIV replication and host cell interactions. This focus will help to guide selection of structure determination targets. The proposed research should aspire to achieve a comprehensive structural analysis of a particular aspect in the biology of HIV-host cell interactions, for example, "uncoating" or "assembly." This may be a continuation of the previous focus of a Center or a new focus for new or renewal applications. A change in focus for a previously funded Center must be sufficiently justified. A judiciously selected set of structures will provide a sufficiently extensive and detailed framework for interpreting, integrating, and guiding functional research related to that aspect of HIV biology. Through such a focused approach, a deep and definitive understanding of that aspect of HIV biology should emerge that then may be capitalized effectively for therapeutic strategies. Since in certain cases related systems, such as other lentiviruses, may be more tractable for structure determination, work on such is acceptable. In these cases, the work must contribute demonstrably to our understanding of HIV biology and provide lessons that can be applied to the development of anti-HIV therapeutics.

Collaboration

Each Center must actively collaborate with the biological community. 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 biological 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 scientists studying HIV/host interactions. These collaborators should be able to enter the structure determination pipeline at several points, from the provision of clones to actual purified complexes. The collaborators expertise in the biological aspects may also be important as the Centers. The goal is to mesh structural and functional studies of HIV host interactions such that they inform and build on each other in pursuit of effective anti-HIV therapeutics. Thus, it is expected that potential competitors will collaborate to the benefit of the project as a whole.

Collaborations and formal interactions are also highly encouraged between Centers and NIH-funded Centers for AIDS Research (CFAR), and the NIAID-funded Center for HIV/AIDS Vaccine Immunology (CHAVI), to both link Center efforts to HIV biology and to facilitate activities toward translational research and drug target validation. Centers may also collaborate with government researchers and Centers, e.g., 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.

Collaborative Development Program

To foster at least a minimum number of these collaborations, each Center will include a Collaborative Development Program. This development program will draw upon a fund, representing approximately 10% of the direct costs of the award, to be included in the budget. The Center will establish, as a part of its management program, a mechanism for the solicitation and award of development grants, subject to final approval by the NIGMS program official. To encourage recipients transition to independent funding, these awards should be of limited duration. Development grants may NOT be awarded to foreign components. Consistent with NIGMS mission of training and mentoring, development awards should be targeted to the recruitment and mentoring of early stage investigators. Collaborative Development Program award recipients must be at the level of faculty or its equivalent. Students and postdoctoral fellows are not eligible. Centers will also establish outreach and data sharing/dissemination mechanism(s) for the biological and collaborative community to have timely access to all data generated in the Center as appropriate and consistent with achieving the goals of the program.

Also, in accordance with the NIGMS mission to promote the training of the next generation of scientists, each Center should provide activities for students, postdoctoral fellows, and early stage investigators. Such activities may include seminars and journal clubs that cover the areas of focus for the Center and HIV structural biology in general. Consistent with the NIGMS mission to include underrepresented populations in the biomedical research workforce, each Center should endeavor to maintain an open and inclusive environment for these activities.

Technology Advancement

Each Center is required to have a technology effort designed to push the state-of-the-art in structure determination and dynamics. Characterization of macromolecular complexes, particularly when such complexes include nucleic acids, carbohydrates or lipids, pushes the current state of the art, both in terms of the technology needed for structure determination and the biology needed to produce sufficient material for analysis. Hence each Center also will work toward advancing the state of the art for the determination and characterization of structures of macromolecular complexes. Methods that characterize the dynamics of such 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 modern single-particle and correlative microscopy methods, which are being used increasingly to examine biological processes in vivo. Collaboration with scientists with demonstrated expertise in these methods is recommended strongly.

Center Organization

Centers are anticipated to be organized primarily around projects that will perform the studies towards the overall aims of the Center. Where multiple and/or complementary expertise is required, project investigators and other collaborators will work in concert to overcome obstacles to achieving the Center aims. Projects can also potentially utilize cores, established if necessary to provide services and/or facilities vital to the efforts of one or more projects. Such services could include X-ray crystallography, cryo-electron microscopy, NMR spectroscopy, etc. Both projects and cores will be devoted toward the goals of the Center as a whole rather than pursuing studies specific to that single component.

Overall success of this program depends critically on the success of each Center, the accomplishments of collaborating investigators and on the ability of the entire program to work in concert. Therefore, each Center will appoint an advisory committee in consultation with and subject to the approval of the NIGMS Program Official. This advisory committee will meet at least once a year and give advice directly to the Center. The NIGMS Program Official will attend each meeting of the advisory committee as an observer. Candidates for the advisory board should not be named in the application or solicited prior to award. In addition, NIGMS will appoint an advisory committee to oversee the operation of the entire network. That committee will function as a working group of the National Advisory General Medical Sciences Council. Members of this committee will be appointed directly by the Program Officials of NIGMS and will give advice directly to NIGMS. The NIGMS committee will meet at least annually. Representatives from each Center are required to attend.

To ensure coordination and cooperation among the funded Centers and the other members of the scientific research community working in areas germane to their mission, an annual scientific meeting will be held. Attendance of the PD/PI and key participants from each Center is required. Attendance of key collaborating investigators is highly encouraged.

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

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• 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) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

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).

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

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

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

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

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Michael Sakalian, Ph.D.
Telephone: 301-594-0828
Fax: 301-480-2004
Email: sakalianm@mail.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (Use for Administrative Core)	6
Project	6
Core	6

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 1
• Project: required
• Core: optional

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

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

Complete entire form.

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

Follow standard instructions.

Enter primary site only.

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

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

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

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

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

Specific Aims: Provide the specific aims for the entire research portion of the Center. What are the goals to be achieved within the biological theme? What technology or technologies will be developed to achieve these goals?.

Research Strategy: In general terms, describe how the projectswill contribute to the overall aims of the Center. Include a discussion of the contribution of the cores to these efforts. Discuss also 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 various projects and/or cores will contribute in a concerted manner toward the Center s goals. Provide a comprehensive overview of how Center components and collaborators, both developmental and outside, will coordinate their efforts..

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 modifications:

• 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 publically accessible resource such as the EMDB.

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

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

When preparing your application in ASSIST, 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.

• 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. Senior/Key persons are the faculty-level (or equivalent) Center investigators. Do NOT list junior individuals (students, postdocs, or technicians) as key personnel.
• 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 Project in the context of the overall goals and biological theme of the Center. What technology or technologies will be developed to achieve these goals?

Research Strategy: Detail the approach to be taken to further knowledge on the biological theme. Discuss also the technology development focus, if applicable, for the Project. For both the biological theme and the 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. If applicable, provide a report of the progress since the last competitive award. Describe how these results have advanced the field. 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 developmental and outside of 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 modifications:

• 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 publically accessible resource such as the EMDB.

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

PHS Inclusion Enrollment Report (Project )

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

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

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. Senior/Key persons are the faculty-level (or equivalent) Center investigators. Do NOT list junior persons (students, postdocs, or technicians) as key personnel
• 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 and biological theme of the Center

Research Strategy: Detail the function of the 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, both developmental and outside of the Center.

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 modifications:

• 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 publically accessible resource such as the EMDB.

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

PHS Inclusion Enrollment Report (Core)

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

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

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

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

List all performance sites that apply to the specific component.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Center 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.
• Senior/Key persons are the faculty-level (or equivalent) Center investigators. Do NOT list junior persons (students, postdocs, or technicians) as key personnel.
• The support of a Center coordinator, who will attend to the day-to-day operation of the Center, is strongly encouraged.

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

Because of the complex nature of these Centers, the Project Director/Principal Investigator must devote at least 25% of his/her effort to the entire Center.

It is essential that sufficient travel funds be allocated in the budget for advisory board meetings, the yearly structure meeting at NIH, and the collaborations envisaged.

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: Briefly outline the goals for the Administrative Core of the Center. Include a brief description of the Collaborative Development program, its priorities, and implementation.

Research Strategy: Detail the management plan for the entire Center, its Collaborative Development Program, and its collaborations with other Centers and the community at large. Describe the roles of the PD/PI, the Project/Core Leads, Collaborators, and Administrative Assistant. Describe the management structure of the Center, its decision making process(es) and the mechanism for resolving conflicts. Describe the scientific goals of the Collaborative Development Program. What will be the size and scope of the development awards? Describe the process for soliciting, reviewing, and selecting development projects, as well as the expertise of the review panel. Note that foreign applicants are not permitted for development awards. 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 Committee. Do not name or solicit advisory board candidates prior to award.

Include also a description of the activities the Center will provide for students, postdoctoral fellows, and early stage investigators. Such activities may include seminars and journal clubs that cover the areas of focus for the Center and HIV structural biology in general. Consistent with the NIGMS mission to include underrepresented populations in the biomedical research workforce, 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 investigator, in sister centers or from the community at large, 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.

PHS Inclusion Enrollment Report (Administrative Core)

Not Applicable.

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.

Collaborative Developmental Program funds will be restricted for that purpose and may not be used or rebudgeted without NIH approval.

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: https://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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

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

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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

See more tips for avoiding common errors.

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

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

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

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 Center 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 Center that by its nature is not innovative may be essential to advance a field.

Does the Center address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the Center? If the aims of the Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

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

Does the 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?

Is the overall strategy well-reasoned and appropriate to accomplish the specific aims of the Center? Is the Center organized in a fashion to ensure success through a concerted effort among all the investigators? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the Center involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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

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

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

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

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

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

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

Not Applicable

For Renewals, the committee will consider the progress made in the last funding period.

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.

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

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

For Centers 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.

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

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 there a strong scientific premise for the project? Is the project necessary to the Center and the attainment of its goals? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?

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

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 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 children, 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? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

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

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

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

Not Applicable

For Renewals, the committee will consider the progress made in the last funding period, including the quality of the publications listed in the Progress Report Publication List.

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.

For applications containing foreign components (as defined in the NIH Grants Policy Statement), reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

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

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the core 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 core 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 core address an important problem or a critical barrier to progress in the field? Is there a strong scientific or organizational premise for the core? Is the core necessary to the Center and the attainment of its goals? If the aims of the core are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?

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

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 core? 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 core is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Is this core well justified as a contributor to goals of the Center and its projects? Is it well integrated into Center efforts and that of collaborators? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the core involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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

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

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

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

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

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

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

Not Applicable

For Renewals, the committee will consider the progress made in the last funding period.

Not Applicable

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

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

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

For cores 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.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Adminstrative Core to fulfill its intended roles for the functioning and success of the Center, 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, an administrative core that by its nature is not innovative may be essential to advance a field.

Does the proposed core address the needs of the research Center that it will administer? Is the scope of activities proposed for the core appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the Center? Is the Collaborative Development Program likely to have an impact on the Center and on the careers of award recipients? Are the plans for outreach and collaboration, beyond the Collaborative Development Program, likely to have a significant effect onthe field at large?

Are the Core Lead(s) and other personnel well suited to their roles in the core? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing research? Do the investigators demonstrate significant experience with coordinating collaborative basic research? Do the multiple Center investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

Does the application propose novel organizational concepts or management strategies in coordinating the research Center the core will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts or management strategies proposed?

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research Center the core will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the Center, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the Center is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the Center? Are an appropriate plan for work-flow and a well-established timeline proposed? Are the plans for engagement and collaboration with the community adequate to influence the wider field? Are the Center plans for activities for students, postdoctoral fellows, and early stage investigators appropriate and consistent with the NIGMS mission to promote the training of the next generation of scientists? Are such activities open and inclusive for populations underrepresented in the biomedical research workforce?

Is the Collaborative Development Program plan structured to augment the goals of the Center? Are the plans for solicitation and selection of awards appropriate? Are there adequate institutional plans and procedures to assure compliance of developmental awards with applicable federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

Will the institutional environment in which the core will operate contribute to the probability of success in facilitating the research Center it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the core proposed? Will the core benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

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

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

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

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

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

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

Not Applicable

For Renewals, the committee will consider the progress made in the last funding period. Was the previous Collaboarative Development Program successful? Did inclusion of award recipients benefit the Center? Did these persons transition to independent funding? Was there an impact of wider collaborations and engagement on the field? Did the community outside the Centers benefit from Center efforts?

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 cores 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 Center for Scientific Review 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 General Medical Sciences Council. The following will be considered in making funding decisions:

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Awardee-selected projects require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with a copy of the Collaborative Development Project application, including the recipient's Other Support information.
• If applicable, IACUUC approval and a completed Vertebrate Animals section must be provided according to the instructions and guidelines provided in the Research Instructions and Worksheet for the Vertebrate Animals Section (VAS).
• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• 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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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. Progress reports should briefly describe the status of Collaborative Development projects, including data and safety monitoring, and should notify NIH of serious adverse events and unanticipated problems.

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

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

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

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Elizabeth Church, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3201
Email: elizabeth.church@nih.gov

Michael Sakalian, Ph.D.
National Institute of General Medical Sciences (NIGMS)
Telephone: 301-594-0828
Email: sakalianm@nigms.nih.gov

Raymond Jacobson, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-996-7702
Email:jacobsonrh@csr.nih.gov

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: adevine@mail.nih.gov

E.C. Melvin
National Institute of General Medical Sciences (NIGMS)
Telephone: 301-594-3912
Email: melvine@nigms.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.