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

This Funding Opportunity Announcement (FOA) on the Systems Approach to Immunity and Inflammation solicits applications to develop a comprehensive understanding of innate and adaptive immune responses triggered by pathogens, adjuvants, or vaccines. The basis of the research program will be forward genetic screens of mutant or genetically diverse mice, combined with systems immunology analyses, to identify previously unappreciated key immune regulatory genes, signaling pathways, or mechanisms, which will be validated in human cells and tissues. The long-range goal of this program is to advance our understanding of immune response dynamics following infection with a pathogen or administration of an adjuvant or vaccine; and to provide foundational information that can be used for development of novel translational approaches, including production of vaccines and immune-based therapeutics. A critical objective of this program is to maximize scientific exchange and accelerate research through the rapid and timely dissemination of research data, protocols, and animal models to the broader research community. Data generated through this initiative will be deposited into public portals, such as ImmPort; and new mouse strains or other animal models will be provided to repositories such as the Mutant Mouse Regional Resource Centers or commercial repositories.

The National Institute of Allergy and Infectious Diseases (NIAID) is strongly committed to building a comprehensive understanding of the human immune system as it responds to infection, vaccination, allergens, and other antigenic challenges. One powerful approach to building a deeper understanding of human immune activation and regulation is through the use of animal studies. Animal studies allow for unparalleled levels of experimental observation and control, which have led to significant advances towards our understanding of the mechanisms governing human immunity. One particularly successful approach toward identifying new immunoregulatory genes and mechanisms has been through the combined efforts of systems biology analysis and forward genetic screens. Systems biology approaches involve rigorously controlled, unbiased, and quantitative collection of large data sets that are then integrated to create models of complex molecular and cellular interactions that provide insights into how the system functions as a whole. Forward genetic approaches seek to identify novel genes or regulatory mechanisms through the phenotypic screening of populations of genetically diverse animals. The discovery of novel immune genes or mechanisms creates a foundation for future hypothesis-driven research to test the functional importance of these elements and to identify potential targets for development of new vaccines or therapeutics. Ultimately, this foundation of knowledge can also be applied to human immune-mediated diseases such as allergy, asthma, transplant rejection, autoimmune diseases, and other inflammatory conditions.

The NIAID has supported dedicated systems immunology programs since 2002 through BAA-NIH-NIAID-DAIT-07-35 and RFA-AI-11-017. These programs have elucidated a number of new pathways, novel genes, and novel functions of known genes/proteins, including the demonstration of the role of newly discovered genes in human disease; over 1000 phenotypes have been found resulting from more than 600 affected genes or quantitative trait loci (QTLs), leading to over 50 peer-reviewed publications in the past 5 years. It is anticipated that in the next 5 years, applying a systems biology approach to the study of immune responses will continue to identify novel genes and regulatory mechanisms, providing important and novel insights into the basic principles guiding how immune networks are designed and operate in normal and pathologic settings.

This Systems Approach to Immunity and Inflammation initiative will support programs to identify novel genes, pathways, and/or regulatory mechanisms that are involved in the activation of innate immunity or induction, generation and/or maintenance of adaptive immune responses triggered by infectious pathogens, adjuvants, or vaccines. Each program must be built upon forward genetic screening of mutant or genetically diverse mice, coupled with systems immunology approaches and human validation in primary cells or tissues, and may be descriptive in nature, discovery focused or hypothesis driven. Since the identified genes, pathways, and/or regulatory mechanisms may also play a role in immune-mediated diseases, this initiative will support limited studies within a program to compare and contrast findings with immune-mediated diseases such as allergy, asthma, or autoimmunity, as long as the studies constitute no more than one-third of the overall research projects or aims. Each U19 Cooperative Agreement will be referred to as a Systems Immunology Program, whereas all U19 Cooperative Agreements supported by this FOA will form the Systems Immunology network.

Forward Genetic Screens of Mouse Models

A centerpiece of this Systems Approach to Immunity and Inflammation initiative is the use of forward genetic screens of existing or newly developed mutant or genetically diverse mice. The majority of the animal work in each Systems Immunology Program will be conducted using mouse models. For some pathogens, other animal models have proven to be valuable models for the study of immune responses to human infectious disease; therefore, an additional animal model may be included within a Systems Immunology Program to complement the murine studies. Studies using an additional mouse model must be well justified by a compelling rationale.

Human Correlation Studies

An essential goal of this FOA is the translation of research findings into a context that is relevant and potentially applicable to human disease. Towards this end, each Systems Immunology Program must include correlation studies to analyze, in human cell or tissue samples, a subset of the immune regulatory genes, pathways, or mechanisms identified in the screens of mouse models. The required human correlation studies may be proposed as a Specific Aim within a Research Project, or as a separate standalone Research Project. The human correlation studies must analyze, in human cell or tissue samples, a subset of the immune regulatory genes, pathways, or mechanisms identified in the high-throughput screens of mouse models. Human cell lines may be used in initial screens; however results must be validated in primary human cells or tissues. While NIAID will support clinical research in this FOA, clinical trials will not be supported.

Bioinformatics

This FOA will also support the development of novel bioinformatic, analytical, or computational tools/models for systems-level analyses.

To promote rapid follow-on discoveries that would benefit public health, all Systems Immunology funded projects will be expected to make available to the wider scientific community all scientific data, new techniques and protocols, research tools, and animal models in a timely fashion. These resources will be deposited in existing public databases and repositories, as designated by NIAID, such as ImmPort, BEI Resources, and the Mutant Mouse Regional Resources. It is expected that all data submitted to ImmPort or other public portals will be released to the public within 9 months of submission or immediately upon publication in a scientific journal, whichever comes first.

Specific Areas of Research Interest

Examples of research areas of interest include, but are not limited to:

• Determination of the functions of novel immune genes and/or proteins that are triggered in the primary or secondary response to infectious pathogens, adjuvants, or vaccines.
• Identification of new functions for known genes/proteins in regulating or contributing to the generation and maintenance of protective or pathogenic immunity in response to infectious pathogens, adjuvants, or vaccines.
• Dissection of the molecules and pathways involved in the regulation of the innate and/or adaptive immune system.
• Determination of the mechanisms that regulate antibody production to pathogens, such as heavy chain class switching, affinity maturation/somatic hypermutation, plasma cell generation and maintenance, and cellular mechanisms required for generation of protective antibody responses.
• Regulation of mucosal immunity triggered in response to infectious pathogens, adjuvants or vaccines.
• Determination of the mechanisms of transcriptional or translational regulation of the innate or adaptive immune system, including, but not limited to the role of MicroRNA or Long non-coding RNA in regulating immune responses to pathogens, vaccines or adjuvants.
• Understanding genomic regulation of immune response genes (e.g., epigenetic, enhancer accessibility/occupancy, structural and spatial organization of chromosomes) and the impact on immunity to pathogens, vaccines, or adjuvants.
• Understanding the interacting cell types and spatial/temporal relationships during immune responses to pathogens, vaccines, or adjuvants.
• Identifying the signal transduction mechanisms and/or networks activated in cells of the innate or adaptive immune system in response to pathogens, vaccines, or adjuvants.

Applications that propose to conduct research in the following areas will be considered non-responsive and will not be reviewed:

• Studies that do not include in vivo forward genetic screening of mouse models.
• Analysis of genes, pathways, or regulatory mechanisms of immunity using only in vitro systems (e.g. in the absence of in vivo mouse studies).
• The sole use of animal models, with no human validation studies.
• Applications that use only human cells or tissues (e.g., in the absence of in vivo animal studies).
• Studies focused on understanding the biology or pathogenesis of infectious agents.
• Studies involving cancer models.
• Systems analysis of innate and adaptive immune mechanisms focused solely on immune-mediated diseases.
• Clinical trials (all phases).

Collaborative Interdisciplinary Teams

The scope of this work requires that interdisciplinary teams be formed that are capable of pursuing coordinated activities that bridge disparate scientific disciplines and expertise. Bringing multidisciplinary groups together creates opportunities for synergy that would rarely happen otherwise. The intention of this FOA is to support integrated, collaborative research teams that have a well-defined, central research focus or objective. The individual Research Projects within each Systems Immunology Program should be clearly interrelated and synergistic so that the research ideas, efforts, and outcomes as a whole will offer a distinct advantage over pursuing the individual Research Projects separately. The research teams within each Systems Immunology Program may be composed of investigators located at one institution, or may be formed through a consortium of different institutions. Frequent interactions and communication within the program are key elements to the Systems Immunology Program’s success.

Pilot Project Program

It is anticipated that awardees will not be able to extensively characterize all immune gene candidates or pathways identified under this program, therefore this FOA will support a Pilot Projects Program to support small-scale studies using the animal models developed under each Systems Immunology Program for the broader research community.

Steering Committee

To promote scientific collaboration, exchange of scientific findings among the Systems Immunology network, and coordination of data dissemination to the broader scientific community, a Steering Committee will be established.

The Systems Immunology Program contains the following components:

Administrative Core: The Administrative Core, headed by the contact PD/PI of the application, will be responsible for the overall management, communication, coordination, and supervision of the Systems Immunology Program. Each Administrative Core will include a cohesive Pilot Project Program to provide opportunities for investigators to study animal models/mutants generated under the Systems Immunology Program. Pilot Project funding is intended to provide modest support that will allow an investigator the opportunity to develop sufficient preliminary data as a basis for an application for independent research support. Pilot Projects are not intended to support participants of the Systems Immunology Program or junior members affiliated with their research groups.

Data Management and Bioinformatics Core (DMBC): This core will provide central data storage, data management and information security services to all researchers within the Systems Immunology Program, and will be responsible for ensuring the timely submission of data and data analyses obtained under this award to the ImmPort database or other public databases designated by NIAID. In addition, the DMBC will be responsible for systems-level analysis of datasets generated by the Research Projects and higher level data analytics. The core may also include study design and statistical support/services for the researchers within the program.

Service Core(s): Service Cores are optional, and are limited to providing standard assays, reagents, technologies, repositories, or other services to Systems Immunology Program. They are intended to provide investigators with resources and services, and be utilized by at least two Research Projects. Service Cores may not propose the development of new technologies.

Research Projects: Each individual Research Project should reflect a distinct research effort; however, individual Research Projects must be clearly interrelated and synergistic so that the research ideas, efforts, and outcomes of the program as a whole will offer a distinct advantage over pursuing the individual Research Projects separately.

Members of each Systems Immunology Program will meet annually in the Bethesda, Maryland area to provide the latest update to the Systems Immunology network and NIH staff on their research, to exchange ideas and information, and discuss collaborations. Meeting participants will identify the group's tangible resources, capabilities, and needs to advance overall program goals.

Timelines and Milestones: Applicants will be required to provide a "Timelines and Annual Milestones" document, with clearly stated interim and long-term objectives, and annual milestones to be achieved during the term of award (e.g., forward genetic screening of mice, human validation, data deposition into ImmPort), to be negotiated after review and prior to award.

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:

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) (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.

An individual can be the PD/PI on only one application submitted to this FOA.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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

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

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

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

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

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

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

The letter of intent should be sent to:

Paul Amstad, Ph.D.
Telephone: 240-669-5067
Fax: 301-480-2408
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core (use for Administrative Core)	6 pages
Core (use for Data Management and Bioinformatics Core, Service Core[s])	6 pages each
Project (use for Research Projects)	12 pages each

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, 1
• Administrative Core: required, maximum of 1
• Data Management and Bioinformatics Core: required, maximum of 1
• Service Core(s): optional, maximum 3
• Research Projects: required, minimum 2, maximum 3

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

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

Complete entire form.

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

Follow standard instructions.

Enter primary site only.

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

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

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

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

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

Specific Aims: Briefly describe the overall specific aims of the proposed Systems Immunology Program.

Research Strategy: Provide an overview that succinctly discusses the key scientific aspects of the Systems Immunology Program and how the proposed program satisfies the purpose and objectives of this FOA. A well-defined, central research focus or objective should be described, as well as the significance, innovation, structure, and approach of the overall Systems Immunology Program. Explain how the proposed Research Projects, Data Management and Bioinformatics Core, Service Cores (if proposed), and Administrative Core will work together to address the overall goals and aims of the program and why the program would be more effective at accomplishing these goals than if the Research Projects were conducted independently.

Letters of Support: Provide any letters of support specific to the Overall component.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix: 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 Admin Core.

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

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

List all performance sites that apply to the specific component.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Administrative Core must be headed by the contact PD/PI of the application.
• The Administrative Core Lead may also lead one Research Project, one Service Core, or both one Research Project and one Service Core. The Administrative Core Lead may not lead the Data Management and Bioinformatics Core.
• Include details of the experience and ability of the Administrative Core Lead and key personnel to manage the overall Systems Immunology Program.

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

The budget of the Administrative Core must include the following:

• Funds to accommodate travel by the PD(s)/PI(s) to attend an initial kick-off meeting and subsequent 2-day annual meetings to review progress, which will be held in Bethesda, Maryland.
• Funds to support deposition of research reagents and/or animal models to existing public repositories may be included, as needed, to ensure access of these resources by the broader research community.
• Funds for the Pilot Project Program. A minimum of $100,000 in direct costs and no more than $200,000 in direct costs should be reserved for the Pilot Project Program beginning in the second year to fund 2-3 projects per year, from years 2-5 of the parent award.
• Direct costs for Pilot Projects should be included in the Other Direct Costs category.
• Funds to support the management of the Pilot Project Program.
• Publication costs for the Systems Immunology Program.

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 proposed activities and services of the Administrative Core. Describe how the work to be completed will support the goals of the Systems Immunology Program.

Research Strategy: Include a detailed plan for efficient management of the Systems Immunology Program's research and administration, ensuring appropriate prioritization of resources, problem identification and resolution, establishment of a strong collaborative environment, and effective sharing of resources within the Systems Immunology Program and Network as appropriate.

Include the following:

• A plan that describes the management of the program, including the administrative and organizational structure.
• Plans for coordination and communication among Research Projects, the Data Management and Bioinformatics Core, and proposed Service Core(s).
• Plans for acting as the primary contact for interactions with the NIH, to include: organizing quarterly teleconferences with the NIAID Program Staff, assisting NIAID Staff with site visits and annual meetings, coordinating travel to annual meetings, and preparing and submitting annual progress reports.
• Plans for internal data exchange and resource allocation.
• A description of the Pilot Project Program, through fiscal administration and management of Pilot Project funds. The description of the process for the solicitation and review of Pilot Projects must include:

• Methods to be used for soliciting applications for Pilot Project opportunities

• Process for application submission from interested investigators not supported by the Systems Immunology Program, including: research scope of the studies to be submitted, frequency of application submission, amount of budget caps per application; and timeline from solicitation to funding.
• Process for Pilot Project review, and internal decision-making processes. Include a process for how open competition and fairness to applicants will be preserved.
• Plans for communicating with the NIAID Project Collaborator regarding applications received by the Pilot Project Program and those recommended by the Systems Immunology Program for support.
• Plans for the distribution and tracking of funds upon approval by NIAID and the interaction with the institutions that will receive the funds from the Pilot Project Program.
• Plan/methods for tracking the progress of funded Pilot Project awardees and evaluation of the overall success of the Pilot Project Program. Procedures, formats, and timelines for reporting the status of Pilot Projects to the NIAID and Systems Immunology network.
• A description detailing how the Pilot Project Program will provide an ample opportunity for investigators to use the resources or discoveries generated by the Systems Immunology Program.
• Specific Pilot Projects should not be described in the application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix: 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 (Administrative Core)

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

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

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

SF424 (R&R) Cover (Data Management and Bioinformatics Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Data Management and Bioinformatics Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management and Bioinformatics Core)

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

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

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

Project /Performance Site Location(s) (Data Management and Bioinformatics Core)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Data Management and Bioinformatics 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.
• The Core Lead of the Data Management and Bioinformatics Core must not also lead the Administrative Core, a Research Project, or a Service Core.

Budget (Data Management and Bioinformatics Core)

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

Include the following:

• Funds to support central data storage, data management, and information security systems for the Systems Immunology Program; and to support the timely submission of data, data analyses, and bioinformatics/computational tools to the ImmPort database, or other databases designated by NIAID.
• Funds for the development and maintenance of a public website.
• Funds to support travel of the Core Lead to the Systems Immunology network kick-off and annual meetings.

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

PHS 398 Research Plan (Data Management and Bioinformatics Core)

Specific Aims: Describe the specific aims of the proposed Data Management and Bioinformatics Core. In addition, state how these aims support the specific aims of the Systems Immunology Program.

Research Strategy: Include a description of the following:

• A plan to establish and maintain tools that are technologically up-to-date for systems-level analyses of datasets generated by the Research Projects.
• A description of the process by which existing bioinformatics tools will be used to analyze and interpret project data.
• A plan and timeline for depositing data into ImmPort.
• A plan to develop and maintain a public website that will provide an overview of the Systems Immunology program. The website must include information about, and the web links (where appropriate) to, access animal models, reagents, experimental protocols, newly developed analytical or computational tools/models, and data (raw and processed) generated through the Systems Immunology Program.
• A plan for interacting with the Project and Core Leads supported by the Systems Immunology Program.

Letters of Support: Provide any letters of support from Collaborators that are specific to the Data Management and Bioinformatics Core.

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:

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

• The Data Management and Bioinformatics Core (DMBC) should be central to the Data Sharing Plan, which is expected to include information on and the availability of: mouse models and reagents generated by the Program Project, experimental protocols, raw and processed data, and newly developed analysis tools.
• The Data Sharing Plan is expected to include an outline of the process and format proposed for data submission to ImmPort, noting that all data submitted to ImmPort or other public portals will be released to the public within 9 months of submission or immediately upon publication in a scientific journal, whichever comes first.

NOTE: The animal models, reagents, analytical/computational tools, and data generated by the Systems Immunology Program should be deposited in existing repositories or databases, as negotiated with NIAID program staff upon award, such as the Mutant Mouse Regional Resource Centers (MMRCR), BEI Resources, BioModels, the Immune Epitope Database and Analysis Resource and ImmPort.

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 (Data Management and Bioinformatics Core)

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

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

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

SF424 (R&R) Cover (Service Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Service Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Service Core)

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

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

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

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

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Service 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.
• A single investigator may not lead more than one Service Core.
• The Service Core Lead may also lead the Administrative Core, one Research Project, or both the Administrative Core and one Research Project.

Budget (Service Core)

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

• Funds to support deposition of research reagents and/or animal models to existing public repositories may be included, as needed, to ensure access of these resources by the broader research community.
• Funds to support travel of the Core Lead to the Systems Immunology network kick-off and annual meetings with NIAID.

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 (Service Core)

Specific Aims: Describe the specific aims of the proposed Service Core. In addition, state how these aims support the specific aims of the Systems Immunology Program.

Research Strategy: Include the following:

• A description of the facilities, techniques, and skills that the Service Core will provide to the Systems Immunology Program.
• A specific outline of how the Service Core will support at least two of the proposed Research Projects, including an explanation for why the core resources are not otherwise available.
• A description of how the Service Core is connected to the central research focus of the overall Systems Immunology Program.
• A description of how the Service Core will enhance the productivity, cost-effectiveness, and/or research outcome of the Systems Immunology Program.

Letters of Support: Provide any letters of support from collaborators that are specific to the Service Core.

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:

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

NOTE: The animal models, reagents, analytical/computational tools, and data generated by the Systems Immunology Program sites should be deposited in existing repositories or databases, as negotiated with NIAID program staff upon award, such as the Mutant Mouse Regional Resource Centers, BEI ResourcesBioModels; the Immune Epitope Database and Analysis Resource and ImmPort.

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 (Service Core)

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

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

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

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

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

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

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

Other Attachments: If human samples are to be obtained from independently funded ongoing or planned clinical trials, documented approval from the clinical trial director should be provided, to include:

• Synopsis of the parent clinical trial protocol;
• Informed consent forms for ongoing or completed parent clinical trials only (i.e., not applicable for clinical trials that have not completed IRB review at the time of application submission);
• Informed consent forms for the proposed systems immunology studies;
• Reference to ClinicalTrials.gov citation, if applicable.
• Memorandum of Understanding from the clinical trial(s) sponsor, IND holder(s) and Principal Investigator(s) supporting use of the samples in the Systems Immunology Program and adherence to the programs data sharing as appropriate.

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

List all performance sites that apply to the specific component.

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

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• A single investigator may not lead more than one Research Project.
• A Research Project Lead may also lead the Administrative Core, one Service Core, or both the Administrative Core and one Service Core. A Research Project Lead may not lead the Data Management and Bioinformatics Core.

Budget (Research Project)

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

The budget should include:

• Funds to support deposition of research reagents and/or animal models to existing public repositories may be included, as needed, to ensure access of these resources by the broader research community.
• Funds to support travel of the Project Lead to the Systems Immunology network kick-off and annual meetings.

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

PHS 398 Research Plan (Research Project)

Specific Aims: Describe the specific aims of the proposed Research Project. In addition, state how these aims support the specific aims of the Systems Immunology Program.

Research Strategy: Include the following:

• A description of the interactions/synergy with the other Research Projects and Cores.
• A description of the forward genetic screens and mouse models to be used.
• A justification for the inclusion of an additional animal model(s), if proposed.
• A description of the human correlation studies, including the procedures that will be used to select subsets of the immune regulatory genes, pathways, or mechanisms identified in the high-throughput screens of mouse models that will be validated in humans.
• Projects that include development of novel bioinformatic, analytical, or computational tools/models for systems-level analyses, should provide a description of the methods to be developed, including how the tools/models will be validated, and how these novel resources are different from others in the public domain.

Letters of Support: Letters of support should be included, as applicable.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

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

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

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

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

For information on how your application will be automatically assembled for review and funding consideration after submission go to: 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 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 determination of scientific and technical merit and in providing an overall impact score, but will not give separate scores for these items.

• Is the Systems Immunology Program as a whole scientifically compelling?
• Are the overall goals of the Systems Immunology Program significant and focused on studies that meet the objectives of the FOA?
• Are the proposed forward genetic screens central to the Systems Immunology Program, and are they used appropriately to facilitate discovery?
• Are the human correlation studies significant and do they support the Program goals?
• Are the individual Research Projects and Cores clearly interrelated and synergistic?
• Does the Systems Immunology Program as a whole offer a distinct advantage over pursuing the individual Research Projects separately?
• Does the Systems Immunology Program PD/PI have sufficient time, effort, leadership ability, and scientific expertise to develop a successful program of integrated research projects with a well-defined research focus?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Research 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 Research Project. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a Research Project that by its nature is not innovative may be essential to advance a field.

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

Are the Research Project Leads, collaborators, and other researchers well suited to the Research Project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative, 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 Research 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 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 children, justified in terms of the scientific goals and research strategy proposed?

Are the proposed forward genetic screening studies of mouse models and the correlation studies to humans appropriate and do they support the project goals? If an animal model is proposed in addition to the required murine model, is it well justified by a compelling rationale?

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?

Reviewers will provide an overall impact score for each individual cores to reflect an assessment of the likelihood that the core will contribute in an important way to the success of the program.

Reviewers will consider each of the review criteria below, as appropriate for the individual core, in the determination of merit and will give an overall impact sore for each Core but will not give separate scores for each criterion.

Administrative Core

• Is the administrative and organizational structure clearly defined and is it appropriate and adequate to accomplish the objectives of the Systems Immunology Program?
• Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the program appropriate?
• Are plans for communication among the members of the Systems Immunology Program adequate to facilitate collaborative activities?
• Are plans for internal data exchange and resource allocation within the Systems Immunology Program adequate and appropriate?
• Do the Core Lead and other staff possess the expertise and experience relevant for their roles/responsibilities and devote adequate effort?
• Are the plans for a Pilot Project Program adequately described and appropriate? Will the Pilot Project Program provide an appropriate opportunity for investigators to use the resources or discoveries generated by the Systems Immunology Program?

Data Management and Bioinformatics Core

• Is the role of the Data Management and Bioinformatics Core (DMBC) clearly defined and is it appropriate and adequate to accomplish the objectives of the Systems Immunology Program?
• Is an adequate plan provided for the DMBC to provide a systems-level analysis of datasets generated by the Research Projects?
• Does the Core provide well defined, appropriate, and effective plans for interacting with other Research Project and Core Leads of the Systems Immunology Program?
• Is there a strong plan to establish and maintain a technologically up-to-date toolset that can be readily used for systems-level analyses of data generated by the Systems Immunology Program?
• Are the plan and timeline reasonable for depositing data generated by the Systems Immunology Program into ImmPort or other public databases?
• Is there a clearly defined plan to develop and maintain a public website that provides an overview of the Systems Immunology Program and information about access to mouse models, reagents, experimental protocols, data, and developed analytical tools? Is this plan adequate and sufficient?
• Do the Core Lead and other staff possess the expertise and experience relevant for their roles/responsibilities and devote adequate effort?

Service Core(s)

• Are the resources to be provided by the Service Core(s) clearly defined and are they appropriate and adequate to accomplish the objectives of the Systems Immunology Program?
• Is the addition of a Service Core(s) sufficiently justified? Does it enhance the productivity, cost-effectiveness, and/or research outcome of the Systems Immunology Program?
• Does each Service Core support at least two Research Projects?
• Is the Service Core adequately connected to the central focus of the overall Systems Immunology Program?
• Does the application demonstrate the ability to provide the services proposed by the Service Core? Will the Core services be used effectively?
• Do the Core Lead and other staff possess the expertise and experience relevant for their roles/responsibilities and devote adequate effort?

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.

Not Applicable

As applicable for the project or 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.

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 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.
• Compliance with data- and resource-sharing policies as appropriate.

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 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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Apprising the Project Collaborator of any potential impediments to execution of the goals of the Systems Immunology Program.
• Ensuring successful completion of the data- and other resource-sharing plans as appropriate.
• Distributing mutant mice and other reagents produced by this award to the research community in a timely manner, through appropriate existing repositories (e.g. the Mutant Mouse Regional Resource Centers, BEI Resources, commercial sources, etc.).
• Depositing data into ImmPort in a timely manner as agreed upon with NIAID, including release of all submitted data to the public.
• Managing the Pilot Project Program.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

• The Project Collaborator will support and encourage the recipient's activities by substantial involvement as partners and facilitators in the process without assuming responsibility that remains with the PD(s)/PI(s).
• The Project Collaborator will work closely with the PD(s)/PI(s) to facilitate collaborations and leverage resources of the Systems Immunology Program.
• The Project Collaborator may withhold or reduce support from any cooperative agreement that fails to achieve its goals according to the milestones agreed to at the time of the award.
• NIAID staff may use information obtained for the preparation of internal reports on the activities of the study.
• 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:

Steering Committee:

• A Steering Committee will be established as part of the Systems Immunology network. One PD/PI from each Systems Immunology Program will be a voting member of the Steering Committee, will participate in all Steering Committee activities, and will follow the policies and procedures developed by the Steering Committee. If an application is a multi-PD/PI application, the remaining PD(s)/PI(s) will serve as non-voting members of the Steering Committee. The Data Management and Bioinformatics Core Lead will serve as a non-voting member of the Steering Committee. The NIAID Project Collaborator will serve as a non-voting member of the Steering Committee.
• The Steering Committee may choose to include the Key Personnel of the individual Systems Immunology Programs as non-voting members of the Steering Committee. NIAID may also appoint additional staff or other investigators to serve on the Steering Committee as non-voting members, as deemed necessary and beneficial to the program overall.
• A Steering Committee Chair will be elected by majority vote from among the Steering Committee voting members. Selection of the Chair will be repeated annually, by majority vote of the voting members.
• Accept and implement policies approved by the Steering Committee.

The responsibilities of the Steering Committee will include the following activities:

• Promote inter-awardee collaboration.
• Establish procedures and standards for interactions with ImmPort, including data submission processes, ontology development etc.
• Establish procedures for the publication and oral presentation of results or data collected collaboratively within the Systems Immunology network. The results of any collaborative work must be approved by the Steering Committee before being made public.
• Discuss potential projects to be funded through the Pilot Project Program.

Dispute Resolution

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: 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: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Kentner Singleton, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5499
Email: [email protected]

Paul Amstad, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5067
Email: [email protected]

Roberta Wolcott
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2964
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.