Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Systems Approach to Immunity and Inflammation (U19)
Activity Code	U19 Research Program Cooperative Agreements
Announcement Type	New
Related Notices	May 26, 2016 - This RFA has been reissued as RFA-AI-16-050.
Funding Opportunity Announcement (FOA) Number	RFA-AI-11-017
Companion FOA	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855; 93.856
FOA Purpose	The primary objective of the program is to use a systems biology approach to develop a comprehensive understanding of innate or adaptive immune responses to infection with and/or vaccination against one or more pathogenic microbes, with a focus on NIAID Emerging/Re-emerging Pathogens of concern to human health. The initiative will support quantitative analyses that will identify and measure dynamic networks regulating immune responses. The basis of the research program will be genome wide screens of mutant mice for identification of key regulatory immune response genes. The studies will be complemented by detailed genomics, proteomics, computational biology and bioinformatics approaches that focus on transcriptional regulation and signaling mechanisms. Investigators will analyze a subset of the newly discovered murine immune regulatory genes in human correlation studies.

Posted Date	March 25, 2011
Letter of Intent Due Date	July 30, 2011
Application Due Date(s)	August 30, 2011
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	January, 2012
Advisory Council Review	May, 2012
Earliest Start Date(s)	August, 2012
Expiration Date	August 31, 2011
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, 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 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 Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), promotes and supports a broad range of research projects focused on basic mechanisms of immune function, including studies of innate and adaptive immunity and the immunological basis of vaccines, adjuvants, and immune-based therapies. As part of its research mission, DAIT announces a program to support a systems biology analysis of innate and/or adaptive immune responses to infection and/or vaccination with a focus on NIAID Emerging/Re-emerging Pathogens. (listed at http://www.niaid.nih.gov/topics/emerging/pages/list.aspx). HIV studies are excluded from this FOA.

The mammalian immune system has evolved to provide an efficient and effective host response during pathogen infection. Cells of the innate immune system are activated directly by recognizing conserved microbial products, such as pathogen DNA, RNA or components of bacterial cell walls. Dendritic cells, natural killer cells, macrophages, and neutrophils are cells of the innate immune system with specialized functions against pathogens, such as the production of anti-microbial molecules or phagocytosis of the pathogen. The innate immune response to infection is very rapid and is instrumental in initiating the adaptive immune response by T and B cells. In contrast to the innate immune response, the adaptive immune system provides long-lived pathogen-specific protective immunity, which may persist for the life of the host. Both T and B cells have receptors that recognize unique components of the pathogen, such as a peptide or protein. Activation of the adaptive immune response leads to the production of antibodies by B cells, the generation of cytotoxic T cells, or cytokine release that helps to clear the pathogen. Robust adaptive immune responses are critical for recovery from infection, as well as vaccine efficacy. In addition, long-lived T and B cell responses, a phenomenon known as immunological memory, are the basis for the use of vaccines to induce pre-exposure protection to specific pathogens.

A systems biology approach will support the study of complex regulatory mechanisms that are crucial for effective immune responses. Immunology is well suited to using a systems biology approach because a number of cellular subsets can be studied and findings can be pursued in well developed model organisms and applied to human immunology and disease. The NIAID has supported dedicated systems biology programs directed at host-pathogen interactions since 2002. These programs have elucidated a number of new pathways, novel genes and their functions, and novel functions of known genes/proteins; including the demonstration of the role of newly discovered genes in human disease. It is anticipated that applying a systems biology approach to the study of immune responses will provide important and novel insights into the basic principles guiding how immune networks are designed and operate in normal and pathologic settings.

The overarching goal of this FOA is to generate and assemble the information required to define common and unique features across immune response pathways, and to integrate the pathways and networks that initiate, sustain, moderate, and resolve immune responses. This systems biology initiative will be a large scale collaborative program that requires multi-disciplinary teams of investigators with expertise in immunology, mouse genetics, genomics, proteomics, infectious disease, bioinformatics, and computational science to better understand the innate and adaptive immune responses to pathogens, as well as the regulatory mechanisms that orchestrate host innate and adaptive immune responses to infection. The research program will be centered on genome wide screens of mutant mice to define key regulatory immune response genes. Investigators will choose a subset of the newly discovered immune regulatory genes from the mouse studies to validate in human correlation studies. Although clinical trials are excluded from this FOA, it is expected that the validation will be performed with primary human cells or tissues. All scientific findings, new techniques, research tools, and project-associated databases will be made available to the wider scientific community to allow for rapid follow-on discoveries that would benefit public health. An educational component will provide workshops or on-line learning environments for researchers to make use of the tools and data generated by the program. It is anticipated that this initiative will lead to a better understanding of the immune response during infection and/or vaccination and will provide detailed information for translational approaches in the discovery and development of vaccines and immunotherapeutics.

At the end of the project period it is expected that each program should have identified and quantified several of the following aspects of host immune responses as they relate to the team’s primary research focus area:

• functions of novel genes/proteins;
• new functions of known genes/proteins;
• interacting cell types and spatial/temporal relationships during responses;
• signal transduction or gene transcription pathways; and
• new potential candidates for biomarkers, diagnostics, or therapeutic targets.

Each application must include both animal and human studies and the development and maintenance of a public website to facilitate the dissemination of novel animal models, reagents, and data, as outlined below:

NOTE: Incomplete and/or non-responsive applications will not be reviewed.

High-Throughput Screens of Mouse Models for the Identification of Key Immune Response Genes.

The systems biology analysis must be based on high-throughput screens of existing or newly developed mouse models for identification of key regulatory immune response genes, supported by detailed genomics, proteomics, computational biology, and bioinformatics approaches to determine the gene products functions in innate and/or adaptive immunity to infection with and/or vaccination against NIAID Emerging/Re-emerging and Biodefense Pathogens (as listed at http://www.niaid.nih.gov/topics/emerging/pages/list.aspx). Studies may also use additional pathogens that pose serious threats to human health, but at least one of the projects proposed in the U19 must be predominately centered on an NIAID Emerging/Re-emerging Pathogen. HIV studies are excluded from this FOA.

Mutagenesis approaches are preferred for development of appropriate mouse models, since these methods do not rely on knowledge of the genetic regulation of an observed phenotype. For example, random mutagenesis with ethylnitrosourea (ENU) has been used successfully by several groups to identify unique innate and adaptive immune response genes involved in immunity to pathogens. These methods were supported by novel screening assays to detect phenotypic changes in immunity, followed by rapid gene identification approaches. Another, relatively untapped resource for large-scale analysis is the wealth of recombinant inbred mouse strains, congenic mouse strains, the Collaborative Cross strains, or the Diversity Outbred strains that exhibit differences in their susceptibility or resistance to infection. More targeted high-throughput genomics methods for the generation of novel mouse models (e.g., targeted mutagenesis of candidate genes, high throughput knock-outs, knock-ins, or deletion mutants) may be utilized, with adequate justification of the benefits these approaches bring to large-scale identification of novel immune response genes.

It is expected that the majority of the animal work will use mouse models. In some instances, other animal models have proven to be better models of human infectious disease. If a second, additional animal model is proposed in these studies, it must be well justified by a compelling rationale for choosing the additional animal model, a discussion of the feasibility of high-throughput screens in the additional animal model, and an explanation of how the reagents, the availability of the animal model, and the genomic information from this animal model will lead to the identification of key regulatory genes that cannot be determined in the mouse models.

All animals and associated reagents generated through the program should be distributed to the research community through appropriate existing repositories, such as the NIAID Taconic Exchange program (http://www.taconic.com/emerging/listing.htm), the NCRR Mutant Mouse Regional Resource Centers (http://www.mmrrc.org), NIAID Biodefense and Emerging Infections Research Resources Repository (http://www.niaid.nih.gov/labsandresources/resources/dmid/midbrr/pages/default.aspx), or commercial sources.

Human Correlation Studies for the Analysis of a Subset of the Immune Regulatory Genes Identified in the Animal Model(s).

Each Program must provide for appropriate translation of research findings into a context that is relevant and potentially applicable to human disease. The research activities to be performed include correlation studies to analyze, in human cell or tissue samples, a subset of the immune regulatory genes identified in the high-throughput screens of mouse models. While human cell lines may be used in initial screens, results must be validated in primary human cells or tissues. The analyses shall be designed to determine the function of immune response genes in human cells that were initially defined in the mouse. These human correlation studies can be proposed as a Specific Aim within a project or as a separate stand alone project. 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. While NIAID will support clinical research in this FOA, clinical trials will not be supported (http://grants.nih.gov/grants/policy/hs/index.htm).

Public Website, Models, Reagents and Data

As part of a required Bioinformatics Core (see below), a description and the availability of animal models, novel reagents, computational tools, and data generated by the funded investigators will be made available to the broader scientific community. Therefore, each funded research team will be required to develop and maintain a public website that includes information on mouse models and their availability, reagents generated through the program, experimental protocols, both raw and processed data, and any newly developed analysis tools for usage by the broader research community.

Educational Component

An educational component must be included within the Administrative and Educational Core (see below) of each U19, to provide training through such means as online tutorials or workshops/symposia hosted at relevant meetings or as stand-alone training. The educational component is intended to provide the research community with enhanced knowledge of systems biology approaches and their applications in the study of the immune system, particularly the utilization of computational analysis tools in the systems biology domain. For example, these could be short training sessions, workshops or symposia (not more than a few days). Topics could include understanding how to use network analysis tools to evaluate immunological data or phosphoflow data analysis and interpretation.

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. By promoting a systematic and quantitative analysis of immune responses on many levels, this initiative offers a unique opportunity to build on current programs and to coordinate these activities toward a common goal. Bringing multidisciplinary groups together creates opportunities for synergy that would rarely happen otherwise. To accomplish a task of this magnitude, it will be necessary for the team to recruit expertise from a multitude of experimental scientific areas, including immunology, molecular and cellular biology, mouse genetics, biochemistry, genomics, and proteomics. Enlistment of strong computational biology expertise will also be key to ensure project success, including bioinformatics and mathematical support that may be necessary to manage the large datasets and network analyses that will be pursued. The research teams may be located at one institution or may be formed through a consortium of different institutions. Frequent interactions and communication within the research team are key elements to the program’s success.

AREAS OF RESEARCH

Because of the nature of this Program some projects may be descriptive or discovery; not all are required to be hypothesis driven. Examples of research areas in the context of infection and/or vaccination that are responsive to this FOA include, but are not limited to, the following (not listed in priority order):

• Regulation of innate immune cell function in response to infections or vaccines (e.g., macrophages, dendritic cells, NK cells, and NK T cells).
• Control of expression of and signaling through immune receptors, such as Toll-like Receptors and NK regulatory receptors, or antigen and costimulatory receptors.
• Dissection of the molecules and pathways involved in the regulation of the innate/adaptive interface.
• Mechanisms that regulate antibody production to pathogens, such as heavy chain class switching, affinity maturation/somatic hypermutation, plasma cell generation and maintenance, and parameters required for generation of protective antibody responses.
• Mechanisms for the generation and maintenance of immune memory in T or B cells.
• Regulation of mucosal immunity in infection or vaccination.
• MicroRNA regulation of the immune system.
• Control and roles of apoptosis in immune response.
• Undertanding the mechanisms that regulate inflammatory responses only in the context of a pathogen infection or vaccination.
• Understanding mechanisms of adjuvants and potential new targets for adjuvant development.

Examples of research areas that are NOT responsive to this FOA include the following areas. NOTE that applications proposing such studies will be considered non-responsive and will not be reviewed.

• Analysis of genes, pathways, or regulatory mechanisms of immunity using only in vitro systems (e.g., absence of in vivo mouse studies).
• Studies using only animal models.
• Studies using only human cells or tissues.
• Bacterial or viral pathogenesis studies in the absence of a detailed analysis of innate or adaptive immunity to the pathogens.
• Systems analysis of innate and adaptive immune mechanisms focusing on immune-mediated diseases (e.g., autoimmunity, allergy, asthma).
• Studies on HIV.
• Clinical trials of experimental therapeutic or prevention strategies/products. However, please note that clinical research involving the use of human samples is required by this FOA (http://funding.niaid.nih.gov/researchfunding/sci/human/pages/hshandbook.aspx).

Additional Information for Multi-Project Applications

This initiative will use the U19 Cooperative Agreement grant mechanism. Essential elements of the U19 include: (1) a minimum of two interrelated Research Projects organized around a central theme; (2) collaborative efforts and interactions among these independent projects and their investigators to achieve a common goal; (3) an Administrative and Educational Core; and (4) a Bioinformatics Core. In addition, one or more optional Scientific Cores are allowed. Lack of synergy and interaction among the Research Projects and Scientific Cores will adversely affect the impact score of a multi-project application, even if the merit of individual projects is high. For detailed instructions for the preparation of the U19 application, please see PHS 398 Application Guide and Supplemental Instruction for the Preparation of Multi-Project Applications under Part 2. Section IV. Application and Submission Information.

Research Projects

Each U19 Program Project application must include at least two inter-related Research Projects. Each Research Project should be prepared according to the standard PHS 398 instructions as modified in the NIAID guidelines for preparing multi-project applications (http://funding.niaid.nih.gov/ncn/grants/multi/index.htm). In addition to the standard scientific description, the interactions among projects and core facilities should be described within each Project. The Projects may be descriptive in nature, discovery, or hypothesis driven, but should provide synergy within the program.

Administrative and Educational Core (required)

An Administrative and Educational Core is required and will support the coordination of efforts across the components of the U19. The Administrative and Educational Core will be responsible for activities not directly supported by the individual projects or scientific cores; including organizing quarterly teleconferences with the NIAID Program Staff, assisting the NIAID Staff with site visits, preparing the annual progress reports or publications from multiple projects within the U19, and coordinating the sharing of resources generated by the program (and budget accordingly). The educational component is intended to provide the research community with enhanced knowledge of systems biology approaches and their applications in the study of the immune system, particularly the utilization of computational analysis tools in the systems biology domain. The PD(s)/PI(s) of the application (or one of the PD/PIs if it is a multi-PD/PI application) must serve as the Leader of the Administrative and Educational Core. The budget for this Core must request funds for the PD(s)/PI(s) to attend an initial kick-off meeting and then semi-annual meetings to review progress that will be held in Bethesda, Maryland.

The budget of the educational component of the program will be included in the Administrative and Educational Core.

Bioinformatics Core (required)

A Bioinformatics Core is required to support at least 2 projects and be responsible for ensuring the availability of the data generated by the funded investigators to the broad scientific community. As part of this Core each funded research program will be expected to develop and maintain a public website and a resource sharing plan that includes information on mouse models and their availability, reagents generated through the program, experimental protocols, and raw and processed data, consistent with achieving the goals of this program. In addition, any analysis tools that are generated through the program should be available at the website. Publically available data analyses tools can be hosted at the website or have links to them at the website. It is expected that a bioinformatics core will also coordinate with the scientific projects within the program to analyze the data generated by the experimental groups. The budget for the development and maintenance of the website should be included in the Bioinformatics Core.

NOTE: Applications that do not contain the required components will not be reviewed.

Scientific Cores (optional)

One or more Scientific Cores may be proposed in a U19 application. Each Scientific Core must be used by at least two research projects. Scientific Cores should be limited to providing standard assays, reagents, technologies, or other available services to investigators. Scientific Cores may include technical services (e.g., flow cytometry, multiplex cytokine analysis, sample collection), animal cores, or other non-administrative activities that directly support the research program.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIAID intends to commit an estimated total of $7 million in FY 2011 to fund 1-3 awards..
Award Budget	Application budgets are not limited, but need to reflect actual needs of the proposed project.
Award Project Period	Scope of the proposed project should determine the project period. The maximum award period is 5 years.

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

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 Organizations)

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) 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 PHS398 Application Guide.

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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

The letter of intent should be sent to:

Quirijn Vos, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3137, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Bethesda, MD 20817-7616 (for express/courier service; non-USPS service)
Telephone: (301) 451-2666
Email: [email protected]

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the appendix files must be sent to:

Quirijn Vos, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3137, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Bethesda, MD 20817-7616 (for express/courier service; non-USPS service)
Telephone: (301) 451-2666
Email: [email protected]

All page limitations described in the PHS398 Application Guide must be followed, with the following exceptions or additional requirements:

• Research Projects are each limited to 12 pages and all cores are limited to 6 pages.

The following section supplements the instructions found in Form PHS 398 for preparing a multi-project grant application. Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research project grant applications, and has no specific instructions for multi-project applications consisting of research projects interrelated by a common theme.

The supplemental instructions for multi-project applications below are divided as follows:

A. General Instructions addresses collaborative efforts among research projects, the administrative and organizational structure as well as the overall facilities and environment, and the overall budget.

B. Specific Instructions for Individual Research Projects describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the Project.

C. Specific Instructions for Cores Describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the Core.

A. General Instructions

All applications must be submitted on Form PHS 398. The multi-project grant application should be assembled and paginated as one complete document.

Items 1 - 14: complete these items as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

Using Page 2 of Form 398; provide a succinct but accurate description (abstract) of the OVERALL multi-project application addressing the major, common theme of the program. Do not exceed the space provided.

List the performance sites where the research will be conducted.

Under "Key Personnel", list the PD/PD/PIof the multi-project application, followed by the Project and Core Leaders of the component research projects and cores, and other key personnel and then other significant contributors.

Do not use Form Page 3 of the PHS 398; a more comprehensive table of contents is needed for a multi-project application.

Bearing in mind that the application will be scientifically reviewed project by project and core by core, prepare a detailed Table of Contents that will enable reviewers to readily locate specific information pertinent to the overall application as well as to each component research project and core. A page reference should be included for the budget for each project and each core. Further, each research project should be identified by number (e.g. Project 1), title, and responsible Project Leader, and each Core should be identified by letter (e.g. Core A), title, and responsible Core Leader. The page location of a COMPOSITE BUDGET should be indicated in the "Table of Contents."

Do not use Form Page 4 of PHS Form 398. Instead, using the suggested format presented below, prepare a Composite Budget For All Proposed Years of Support. (Justification for budget elements should not be presented here but in the individual budgets of the projects and cores.)

SAMPLE: Consolidated Direct Cost Budget for All Proposed Years of Support

Component	Year 1	Year 2	Year 3	Year 4	Year 5	All Years
Project 1. Invest.	125,000	130,000	135,200	140,608	146,232	677,040
Project 2. Study	125,000	130,000	135,200	140,608	146,232	677,040
Project 3. Develop.	100,000	104,000	108,160	112,486	116,985	541,631
Core A. Admin. Core.	50,000	52,000	54,080	56,243	58,493	270,816
Core B. DNA	25,000	50,000	52,000	54,080	56,243	237,323
Totals	425,000	466,000	484,640	504,025	524,185	2,403,850

Complete the Total Direct Cost line entries for all requested budget periods (years) and the Total Direct Cost for Entire Period of Support entry. Detailed budgets are required within the descriptions of each project and core (see below). If the FOA allows for budget requests beyond 5 years, use a second Form Page 5 to reflect the additional budget years requested.

Biographical sketches of all professional personnel for all components should be placed at the end of the application with the PI/PD first, followed by those of other key personnel in alphabetical order.

Do not complete. Essential information is to be presented in the individual research project and core sections of the application.

Specific Aims (Limited to 1 page.)

List in priority order, the broad, long-range objectives and goals of the proposed Program. Concisely and realistically describe the hypothesis or hypotheses to be tested.

Overall Research Strategy (Limited to 12 pages)

This narrative section summarizes the overall research plan for the multi-project application and is limited to 12 pages. The multi-project application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall Program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems. As the strategy develops, each individual research project and core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique. In addition, provide detailed annual milestones for the major goals and objectives for the Program. If the application is a renewal, the Program Overview (Research Objectives and Strategic Plan) section should also highlight past performance and the major accomplishments from the prior funding period as described in the PHS 398 Instructions. Preliminary studies and/or progress reports must be contained within the page limits of the Research Strategy section.

One Checklist, placed at the end of the application, is to be submitted for the entire application.

Refer to Section IV.6. Appendix Materials below, for instructions on submitting appendix materials.

For each project or core in the multi-project application, 3 publications plus other approved material are allowed.

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each research project.

For each individual Research Project, include:

Face page (see special instructions, below)

Description & Key personnel (PHS 398 Form Page 2)

Table of Contents (PHS 398 Form Page 3)

Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications

Research Plan

Resources

The Face Page of the 398 Form should not be used as a cover page for individual research projects within a multi-project application. Instead, use the PHS 398 continuation page to create a "Cover Page" containing selected data about each individual research project. This Cover Page will demarcate each individual research project and should contain the following information items (these are a subset of the information provided on a PHS 398 Face Page):

• Project Number and Title: (e.g., 1. Preclinical Evaluation of HIV Microbicides)
• Name of Project Leader: (e.g., Jones, Roberta A.)
• Human Subjects: (Yes or No)
• If Yes:
• Exemption number, -or-
• IRB Approval Date (e.g., 12/13/2006,or "Pending"), and Federalwide Assurance (FWA) number
• Vertebrate Animals: (Yes or No)
• If Yes:
• IACUC Approval Date (e.g., 11/17/2006, or Pending) and Animal welfare assurance number:
• Proposed Period of Support:
• From: (mmddyy - e.g., 07/01/2007)
• To: (mmddyy - e.g., 06/30/2112)
• Costs Requested for Initial Budget Period: (e.g. 07/01/2007-06/30/2008)
• Direct Costs: (e.g., $ 150,000)
• Total Costs: (e.g., $162,000)
• Costs Requested for the Entire Budget Period: (e.g., 07/01/2007-06/30/2112)
• Direct Costs: (e.g., $700,000)
• Applicant Organization (full address)

Provide a Description (abstract) of the research proposed in the individual research project according to the instructions on Form Page 2 of PHS Form 398. In addition, the abstract should contain a brief description of how the individual research project will contribute towards attainment of the multi-project Center objectives.

List the performance sites where the research will be conducted.

Under "Key Personnel", list the Project Leader, followed by other key project personnel, and then other significant contributors.

Prepare a Table of Contents for the research project using Form Page 3 of the PHS 398.

Prepare a detailed budget and justification for the research project using Form Pages 4 and 5 of the PHS 398.

(a minimum of two individual research projects are required)

Specific Aims (Limited to 1 page.)

List, in priority order, the broad long-range objectives and goals of the proposed project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the individual research project's relationship to the Program’s goals and how it relates to other projects or cores.

Research Strategy (Limited to 12 pages.)

Use this section to describe how the proposed research will contribute to meeting the Center’s goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application.

Organize the Research Strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5. Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information. Experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. Preliminary Studies for new projects must be included as part of the approach section, and must be contained within the page limits of the Research Strategy section.

Provide information on resources available for the project. Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport.) For Early Stage Investigators, describe institutional investment in the success of the investigator. If there are multiple performance sites, describe the resources available at each site. Describe any special facilities used for working with biohazards or other potentially dangerous substances.

Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each proposed core.

For each individual Core, include:

Cover page (see special instructions, below)

Description & Key personnel (PHS 398 Form Page 2)

Table of Contents (PHS 398 Form Page 3)

Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications

Core Services Plan

Resources Format Page

The Face Page of the 398 Form should not be used as a cover page for cores within a multi-project application. Instead, use the 398 continuation page to create a "Cover Page" containing selected data about each individual core. This Cover Page will demarcate each core and should contain the following information items (which are a subset of the information provided on a Face Page - see PHS 398):

• Core Letter and Core Title: (e.g., A. Monoclonal Antibody Production Core)
• Name of Core Leader: (e.g., Smith, Robert A.)
• Human Subjects (Yes or No)
• If Yes,
• Exemption Number, -or-
• IRB Approval Date (e.g., 5/14/06, or Pending), and Federalwide Assurance (FWA) number
• Vertebrate Animals (Yes or No)
• If Yes,
• IACUC Approval Date (e.g., 4/15/07, or Pending), and Animal welfare assurance number
• Proposed Period of Support
• From: (mmddyy, e.g., 07/01/2007)
• To: (mmddyy, e.g., 06/30/2012)
• Costs Requested for Initial Budget Period
• Direct Costs (e.g. $50,000)
• Total Costs (e.g. $70,000)
• Costs Requested for the Entire Budget Period
• Direct Costs (e.g. $212,323)
• Total Costs (e.g. $297,252)
• Applicant Organization (ABC University; 111 Main Street; Anywhere, Else 99999)

The following are specific instructions for sections of the PHS 398 application form that are to be completed differently than usual. For all other items in the core application, follow the usual PHS 398 instructions.

Provide a Description (abstract) of the core activities and services according to the instructions on Form Page 2 of the PHS 398. In addition, the abstract should contain a brief description of how the core services will contribute towards attainment of the objectives.

List the performance sites where the core activities and services will be conducted.

Under "Key Personnel", list the Core Leader, followed by other key core personnel, and then other significant contributors.

3. Table of Contents

Prepare a Table of Contents for the core using page 3 of Form PHS 398.

Prepare a detailed budget and justification for the core using Form Pages 4 and 5 of the PHS 398.

Required minimum cores: Administrative and Educational Core, Bioinformatics Core; optional cores: Scientific Cores

Specific Aims (Limited to 1 page.)

List in priority order, the broad, long-range objectives and goals of the proposed Administrative and Educational Core, Bioinformatics Core, or Scientific Cores. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the core’s relationship to the Program s goals and how it relates to the individual research projects or other cores in the application.

Core Services (limited to 6 pages)

Use this section to describe how the proposed core activities will contribute to meeting the Center's goals and objectives and explain the rationale for selection of the general methods and approaches proposed to accomplish the specific aims. In addition, this section should indicate the relevance of the core to the primary theme of the application.

Organize the Plan in the specified order as stated in the PHS 398 Instructions, Section 5.5. Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information. Experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. Preliminary Studies for new cores and progress reports for renewal cores in a renewal application must be included as part of the approach section and must be contained within the page limits of the Core Services Plan section.

Provide information on resources available for the core. Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport.) For Early Stage Investigators, describe institutional investment in the success of the investigator. If there are multiple performance sites, describe the resources available at each site. Describe any special facilities used for working with biohazards or other potentially dangerous substances.

Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) as provided in the PHS398 Application Guide.

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the PHS398 Application Guide.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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 received on or before the due dates in Part I. Overview Information.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NIAID, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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/priority 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).

Is the program as a whole scientifically compelling? Are there coordination and synergy of the individual research projects and cores towards the achievement of the central objectives of the program? Are the overall program goals significant and focused on studies that meet the objectives of the FOA? Will the integration of the individual projects into a single program be more beneficial than pursuing each project independently? Are the proposed milestones reasonable and achievable? If additional animal models (non-mouse) are proposed are the need and use adequately justified? Do(es) the PD/PI (multiple PDs/PIs) have the leadership and scientific ability to develop an integrated and focused research program? Are the qualifications, experience, and commitment of investigators responsible for the individual research projects or cores and their contribution to the program, including their ability to devote time and effort to the program adequate? Is there adequate evidence of sufficient institutional support for the PD/PI (multiple PDs/PIs) in terms of laboratory space, equipment and other resources? For applications designated multiple PDs/PIs, is the Leadership Plan both adequate and appropriate to ensure that there will be sufficient coordination and communication among the PDs/PIs?

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

Protections for Human Subjects

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed program involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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.

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

As applicable for the program 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/priority score.

Applications from Foreign Organizations

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.

Select Agent Research

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).

Resource Sharing Plans

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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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/priority 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 five scored review criteria, and additional review criteria (as applicable for the project proposed).

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

Investigator(s)

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

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

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

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

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

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

For the Administrative and Educational Core, is the administrative and organizational structure appropriate and adequate to achieve the goals of the proposed program? Is the management plan for fiscal accountability and communication within the program appropriate? 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 U19 adequate to facilitate collaborative activities? Are the personnel and plans for the educational component appropriate and adequately described? Will the educational component provide the research community with enhanced knowledge of systems biology approaches and their applications in the study of the immune system, particularly the utilization of computational analysis tools in the systems biology domain? Do the PD/PI and Key Personnel commit sufficient time and effort to adequately manage the Program?

For the Bioinformatics Core, is the proposed plan for the development and maintenance of a public website that includes information on mouse models or any additional proposed animal models and their availability, reagents generated through the program, experimental protocols, both raw and processed data, and analysis tools for usage by the broader research community adequate and reasonable? Does it support at least two research projects? Is the plan for resource sharing adequate?

For the Scientific Core(s), is it sufficiently justified? Does it support at least two research projects? Is the core adequately connected to the central focus of the overall program? Are the facilities or services provided by the core (including procedures, techniques, and quality control) high quality? Will the services be used effectively? Are the core leader and key personnel well qualified and is there an adequate commitment of time?

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

Protections for Human Subjects

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed Project or Core involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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.

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/priority score.

Applications from Foreign Organizations

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.

Select Agent Research

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).

Resource Sharing Plans

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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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 NIAID Scientific Review Group(s) , in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments 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/priority score.
• Will receive a written critique.

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 Councill. 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/PD/PIwill be able to access his or her Summary Statement (written critique) via the eRA Commons.

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 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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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:

• Defining the research plan and goals; overseeing/performing the scientific activities of the plan; monitoring the accomplishment of successful completion of milestones within the timeframe and budget proposed; cooperating with NIAID programmatic, technical, and administrative staff, and administratively managing the U19.
• Awardees agree to accept close coordination, cooperation, and participation of the NIAID staff in those aspects of the scientific and technical management of the project described below.
• The awardee is solely responsible for the timely acquisition of all appropriate propriety rights, including intellectual property rights, and all materials needed for the awardee to perform the project.
• The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act).
• Awardees are expected to make new information and materials known to the research community in a timely manner through publications, web announcements, and reports to the NIAID, or other mechanisms.
• If multiple awards are made, one PD/PD/PIfrom each U19 award will be a voting member of the Steering Committee (see below), will participate in all Steering Committee activities, and will follow the policies and procedures developed by the Steering Committee.
• Mutant mice and reagents produced by this award will be distributed to the research community through appropriate existing repositories, such as the NIAID Taconic Exchange program (http://www.taconic.com/emerging/listing.htm), the NCRR Mutant Mouse Regional Resource Centers (http://www.mmrrc.org), NIAID Biodefense and Emerging Infections Research Resources Repository (http://www.niaid.nih.gov/labsandresources/resources/dmid/midbrr/pages/default.aspx), or commercial sources.

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

• A program official from the extramural Basic Immunology Branch of the Division of Allergy, Immunology, and Transplantation will serve as NIAID s Project Scientist for the Systems Biology Program. In conjunction with other NIAID scientific program staff and the Steering Committee, the Project Scientist will provide advice and guidance on technical issues, such as reviewing progress or approving changes in proposed milestones.
• After award of the grants, the NIAID will establish an External Advisory Board (EAB) to advise the NIAID by reviewing, evaluating, and prioritizing the scientific progress of the individual awardees and the network. Applicants should not contact any individuals for the purpose of serving on this EAB, nor should they identify any such individuals in their applications.
• Although applicants can propose scientific advisory boards (SABs) to advise the PD(s)/PI(s) of the individual awards, applicants should not contact any individuals for the purpose of serving on these Scientific Advisory Boards, nor should they identify any such individuals in their applications.
• 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. This Program Officer will monitor program progress, approve changes, have access to data generated under these awards, and may periodically review the data and progress reports. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study. This assigned Program Officer may also serve as the NIH Project Scientist.

Areas of Joint Responsibility include:

Steering Committee

• If multiple awards are made, a Steering Committee will be established to serve as the governing board of a systems biology network. One PD/PD/PIfrom each U19 award 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. An NIAID Project Scientist will serve as a non-voting member of the Steering Committee.
• The Steering Committee will direct collaborative work of the awardees, evaluate the progress and direction of the individual awardees and network, and make recommendations for the continuation or re-direction of projects on an ongoing basis and in consultation with the NIAID.
• In order to maximize the utilization of awardee resources, the Steering Committee may re-budget individual awardee funds, with the approval of the NIAID.
• U19 Project Leaders and other relevant investigators may serve as non-voting members, as determined by the Steering Committee. NIAID may also appoint additional staff to serve on the Steering Committee as non-voting members.
• A Steering Committee Chair will be elected by majority vote from among the Steering Committee voting members. Selection of the Chair will be repeated yearly, by majority vote of the voting members.
• Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.
• The Steering Committee will meet face-to-face during the Annual Scientific Meeting and will also meet by teleconference at intervals to be decided by the Steering Committee and the NIAID.

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

• Define procedures for the evaluation of ongoing research within the network and recommend changes in research direction if needed;
• Promote inter-awardee collaboration; and
• Establish procedures for the publication and oral presentation of results or data collected collaboratively within the Systems Biology Network. The results of any collaborative work must be approved by the Steering Committee before being made public and all publications should provide appropriate acknowledgement of NIAID support.

Semi-Annual Scientific Meetings

• All awardees will participate together in an initial meeting, arranged by the NIAID Project Scientist, to be held soon after award in the Bethesda, Maryland area; and will participate in face-to-face Scientific Meetings of all PDs/PIs to be held semi-annually thereafter.
• The Scientific Meetings are open to members of the network and to NIH extramural staff. These meetings will serve as opportunities for members to provide the latest update on their research, exchange ideas and information, and discuss collaborations among consortium members.
• Meeting participants will identify the group’s tangible resources, capabilities, and needs to advance overall program goals.
• The PDs/PIs are required to give oral presentations at the annual meetings on current and planned activities and projects.
• In addition, NIAID staff may perform annual site visits to the PI’s research facilities.

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 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 Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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.

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Lynda Chiodetti, Ph.D.
Basic Immunology Branch
National Institute of Allergy and Infectious Diseases (NIAID)
Room 6411, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601
Bethesda, MD 20817-6601 (for express/courier service; non-USPS service)
Telephone: 301-451-3119
Email: [email protected]

Quirijn Vos, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3137, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Bethesda, MD 20817-7616 (for express/courier service; non-USPS service)
Telephone: (301) 451-2666
E-mail: [email protected]

Roberta Wolcott
National Institute of Allergy and Infectious Diseases (NIAID)
Room 2244, MSC-7614
6700B Rockledge Drive
Bethesda, MD 20892-7614
Bethesda, MD 20817-7614 (for express/courier service; non-USPS service)
Telephone: 301-451-2685
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 Parts 74 and 92.