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). 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) solicits applications that use a multi-disciplinary systems biology approach to study the molecular interaction networks of the pathogen and the host in association with antibacterial resistance or in response to treatment of antibacterial resistant (AR) infections. Proposed projects are expected to employ high-throughput omics technologies and assays of host responses, robust data management processes, data integration and computational modeling methods. The proposed project’s focus must be on bacterial pathogens with established antibacterial resistance as defined in the Research Objectives section. Increased understanding of the molecular mechanisms of the host and the pathogen associated with AR is critical to combat infectious diseases and for public health preparedness.

Over the past several years, bacterial resistance has increased at an alarming rate. This includes resistance among Gram-negative bacteria, which have acquired new resistance traits rapidly over the past decade. It is recognized that novel strategies are needed to understand the complexity of AR infectious diseases, control the emergence of antimicrobial resistance and facilitate the development of new antimicrobial interventions. Traditional molecular approaches have been used to investigate the biochemical function of individual genes and proteins of pathogens and the host to identify potential drug targets. However, new system-level approaches are now available that comprehensively examine host-pathogen molecular interactions to offer new research strategies to understand and discern cause-effect mechanisms of infectious diseases, and provide a framework for more effective therapeutic development.

The NIAID has made a significant investment in genomic-related activities that provide advanced technologies and comprehensive genomics resources to the scientific community for basic and applied research to rapidly address the Institute's mission (http://www.niaid.nih.gov/topics/pathogenGenomics/Pages/relatedInitiatives.aspx). In 2008 NIAID/DMID launched the Systems Biology for Infectious Diseases Research initiative (http://www.niaid.nih.gov/labsandresources/resources/dmid/sb/pages/default.aspx) to establish projects that develop and utilize a combination of experimental high-throughput omics technologies and computational modeling methods and, furthermore, to encourage a paradigm shift in strategies for infectious diseases research by adopting less traditional, more global approaches. State-of-the-art next-generation sequencing, transcriptomics, proteomics, metabolomics and other high-throughput "omics" technologies enable the efficient generation of very large experimental data sets that can be integrated to build/train predictive computational models of complex biological systems. This vast amount of data presents a number of challenges for data integration and analysis; however, it also provides an unprecedented opportunity for generating robust predictive models of the molecular processes occurring in the pathogen and the host at different stages of infection and treatment.

This initiative will support research projects that utilize a systems biology approach to identify, quantify, model and predict the overall architecture and dynamics of the molecular interactions of AR pathogens and their host during infectious disease initiation and progression or in response to antibacterial treatment. The molecular interaction networks serve as an integrated knowledge base and establish a framework to more efficiently explore the complexity of pathogen-host interactions and the functional behavior of microbial communities that play a role in the response to antibiotics. Systems biology studies of the host microbiome during AR disease and antibiotic treatment are also of interest for this initiative.

Applications focused on the pathogens designated as Urgent Threats in the Centers for Disease Control and Prevention’s Antibiotic resistance threats in the United States, 2013 report (http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf), which include Clostridium difficile, carbapenem-resistant Enterobacteriaceae (CRE) and drug-resistant Neisseria gonorrhoeae, are of highest priority. In addition, applications focused on the bacteria listed in the Serious Threats list in the aforementioned CDC report, with the exception of Mycobacterium tuberculosis, are also responsive to this FOA, especially those focused on the ESKAPE bacteria, i.e., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and extended-spectrum beta lactamase (ESBL)-producing Enterobacteriaceae (e.g., Escherichia coli and Klebsiella). 

For the purpose of this initiative, the systems biology approach consists of repeated cycles of experimental data generation, analysis and integration, modeling of system-wide molecular networks structure and dynamics, predictions of microbial and host systems responses to changes/perturbations/alterations of experimental conditions and experimental validation.

Each research project should be designed around a primary biological hypothesis to be tested using the systems biology approach. Studies using human primary cells and/or clinical samples (i.e. human tissues, human blood, immune components, bacterial isolates) from human subjects with AR infections are strongly encouraged; however studies using the appropriate animal models of human AR disease are also acceptable. Employment of omics and other advanced high-throughput technologies is strongly encouraged to investigate the metabolic, regulatory, signaling and immune responses of the pathogen and the host affected by AR disease or in response to treatment. Examples of omics technologies of interest include, but are not limited to, those for next-generation sequencing, transcriptomics, proteomics, metabolomics, lipidomics, and others. These technologies should be used to conduct not only systems-wide molecular profiling studies, but also more targeted measurements, such as quantitative targeted proteomics  (e.g. MRM: Multiple Reaction Monitoring) or validation of protein/protein or protein/DNA interactions. In addition, development of computational approaches for big-data integration of multiple data types generated by the experimental technologies is supported under this FOA, including, for example, data analysis and visualization tools development. Also, computational modeling of the molecular networks and other cellular subsystems is strongly encouraged. Experimental validation of the new hypotheses generated through the systems biology approach is also of primary interest for this initiative. An example of experimental validation is by testing in an animal model the predicted role of a host factor in antibiotic resistance, through the assessment of the effects on the outcome of the infection of the host gene knockout or by RNA interference.

Rapid and efficient release to the broad scientific community of datasets, analysis tools, computational models, reagents, and other resources generated under the grant in adherence to the requirements and timelines described in the NIAID Data and Reagents Sharing and Release Guidelines (http://www.niaid.nih.gov/LabsAndResources/resources/dmid/gsc/Pages/data.aspx) is strongly encouraged.

Potential areas of research include, but are not limited to, the following:

• The analysis of host/pathogen molecular interaction networks to compare networks responses during infection with AR and non-AR strains and in response to antibiotic treatment.
• Risk assessment for the emergence of antibacterial resistance in animal models of human infection.
• Studies of the molecular processes and biological functions of the host microbial populations during AR infection, treatment and return to homeostasis.
• Identification of host factors, including lipids and metabolites, which contribute or interfere with drug efficacy or toxicity during treatment of AR disease.
• An assessment of disease progression in response to drug treatment derived from molecular expression profiling of clinical isolates from treatment-responsive and unresponsive patients.
• Identification of early biomarkers of host response to treatment, resolution or exacerbation of AR disease.
• Identification of pathogen and host gene targets for rational combination chemotherapy to suppress antibacterial resistance.

Applications including the following studies will be considered non-responsive and will not be reviewed:

• Applications focused on Mycobacterium tuberculosis.
• Projects that focus exclusively on the cellular molecular components and interactions of the pathogen with no consideration of the host, and vice versa. For example, studies that focus uniquely on the identification of molecular signatures of the host immune response will be considered non-responsive; a project proposing only sequencing of bacterial isolates from patients not responding to antibiotic treatment will be considered non-responsive.
• Studies that propose only the use of immortalized cell cultures, but not samples from human or animal tissues.
• Applications addressing infectious diseases caused by bacteria other than those identified above.
• Applications that propose clinical trials.

Steering Committee

A Steering Committee will be established by the NIAID in collaboration with the awardees to review the progress in meeting the goals of all projects funded under this FOA and of the Systems Biology for Infectious Diseases Research initiative. The Steering Committee will also make recommendations for the continuation or re-direction of the funded projects on an ongoing basis and in consultation with the NIAID staff.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download 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.

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. 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:

Eleazar Cohen, Ph.D.
Telephone: 240-669-5881
Fax: 301-480-2408
Email: ecohen@niaid.nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

• For this specific FOA, the Research Strategy section is limited to 30 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

Facilities & Other Resources: 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.

Other Attachments: The following attachment is required for this FOA, and must be included as separate pdf attachment under "Other Attachments".

A. Project Organization and Management Structure Plan: The filename Project Organization and Management Structure Plan.pdf should be used and will be reflected in the final image bookmarking for easy access for reviewers.

Applicants are required to include a Project Organization and Management Structure Plan describing the management structure, the roles and responsibilities of scientific and administrative staff; how resources will be allocated and managed; how fiscal accountability will be monitored; and how effective communication among the key personnel will be established and maintained. It is suggested that this section be no more than 8 pages. Applications lacking this attachment will be deemed incomplete and will not be reviewed.

If applicable to the applicant's proposed research:

B. Human Subjects Research Documentation: The filename Human Subjects Research Documentation.pdf should be used and will be reflected in the final image bookmarking for easy access for reviewers.

If proposing research using human samples, provide copies of the relevant IRB documentation, protocol(s) and consent form(s) related to the human sample collection to be used in the proposed project, if available. 

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

The biosketches for the application should reflect a multidisciplinary research team with the relevant expertise spanning the fields of bacterial infectious diseases, antibacterial resistance evolution and mechanisms, AR diseases, systems biology, omics and other advanced technologies, big-data management and computational modeling, as necessary. Biosketches should also describe past experience with research projects of similar size and complexity as the proposed project.

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

Each PD(s)/PI(s) must expend at least 2.4 person-months effort on the project.

Costs associated with prospective human sample collection are not allowable.

Include travel costs for the PD(s)/PI(s) and key personnel to attend a one-time, two-day kick-off meeting to be held at a location at/near Bethesda, MD or at another NIAID-approved site.

Include travel costs for the PD(s)/PI(s) and key personnel to attend annual 1 2 day Programmatic Meetings beginning in year 2 of the award to share knowledge of innovative technologies and methodologies, and to encourage collaboration. Each awarded Center will assume responsibility for the meetings organization at least once over the award period. These meetings are anticipated to be held at a location at/near Bethesda, MD or at another NIAID-approved site. Costs for organizing the annual meeting should not be included in the budget.

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

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

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

Specific Aims:  List the objectives and goals of the proposed program.  Concisely and realistically describe the hypothesis or hypotheses to be tested.

Research Strategy: This section describes the overall research strategy and explains how the proposed project satisfies the purpose and all objectives of this FOA. Each research project must be designed around a primary biological hypothesis to be tested and validated using the systems biology approach, and must include the following elements:

• Describe the research design, conceptual procedures and analyses to be used to accomplish the specific aims of the project.
• Provide a strong justification for the selection of the pathogen/disease and its association to antibacterial resistance.
• If proposing to use samples from human subjects indicate the samples source and provide the rationale indicating that the sample collection is adequate for the proposed project. For example, provide the number of samples to be analyzed, describe available sample metadata, expected quality and quantity of materials for omics profiling, report the human samples de-identification status, any relevant preliminary work done with those samples, etc.  Studies using human primary cells and/or clinical samples (i.e. human tissues, human blood, immune components, bacterial isolates) from human subjects with AR infections are strongly encouraged; however studies using the appropriate animal models of human AR disease are also acceptable.
• If using animal models, provide a description of how the research findings are applicable and relevant to the study of antibacterial resistant diseases in humans.  
• Describe which omics and other advanced high-throughput technologies will be used to investigate the responses of the pathogen and the host during AR disease and treatment. Explain the rationale for the selection of the methods and approaches proposed, and how these technologies complement each other. Examples of omics technologies of interest include, but are not limited to, those for next-generation sequencing, transcriptomics, proteomics, metabolomics, lipidomics, and others. These technologies should be used to conduct not only systems-wide molecular profiling studies, but also more targeted measurements, such as quantitative targeted proteomics (e.g. MRM: Multiple Reaction Monitoring) or validation of protein/protein or protein/DNA interactions.
• Provide details of the data management system and sample tracking system of the project across all sites involved in the project.
• Describe the processes that will be put in place to ensure rapid and efficient sharing and release of all resources generated by the project.  
• Provide a description of the computational approaches that will be developed and utilized to integrate experimental datasets, which may include the development of data analysis and data visualization tools.
• Provide a description of the computational modeling approaches that will be developed and utilized to investigate the biological systems; and clearly delineate how the experimental data to be generated under the project will inform and improve the models.
• Describe how the computational models of the interaction networks or of other biological systems of interest will be experimentally validated. An example of experimental validation is by testing in an animal model the predicted role of a host factor in antibiotic resistance through the assessment of the effects on the outcome of the infection of the host gene’s knockout or silencing by RNA interference.

Milestones and Timelines: Applicants are required to include Milestones and Timelines with detailed project performance and quarterly timelines and milestones for the proposed work. These should be specific, measureable, and scientifically justified; they should not be simply a restatement of the specific aims. Include discussion on potential delays, and alternates for conducting the study in the face of adverse outcomes or unanticipated problems.

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

• All applications submitted for the January 25, 2015 due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.
• All applications, 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 Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. 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.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). 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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

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.

Important reminders:

All PD(s)/PI(s) 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. See Section III of this FOA for information on registration requirements.

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

Does the project address an important problem or a critical barrier to progress in the field? 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? Do the overall project goals utilize a multi-disciplinary systems biology approach to study the molecular interaction networks of bacterial pathogens with established antibacterial resistance or in response to treatment of antibacterial resistant infections?

Are the PD(s)/PI(s), 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 the level of commitment of the PD(s)/PI(s) and key personnel adequate to manage the overall project? For applications designated multiple PD(s)/PI(s), is the Leadership Plan both adequate and appropriate to ensure that there will be sufficient coordination and communication among the PD(s)/PI(s)?

Do the PD(s)/PI(s), collaborators and other researchers have the appropriate skills for rigorous collection, analysis and interpretation of data to be generated?

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 proposed computational approaches innovative?

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? 

Do the targeted pathogen(s)/disease(s) address the FOA s intent to focus on the most problematic AR pathogens? 

Are the proposed host systems adequate, well-documented and characterized? If using animal models, are the models relevant and appropriate to investigate antibacterial resistant infections?

Are the proposed omics and other advanced technologies well justified, critical and relevant to the project aims?

Are the appropriate statistical plans, power calculations and controls included?

Are the described data management activities sufficient?

Are the proposed computational modeling approaches appropriate?

Is the project’s implementation of a systems biology approach adequate?

Are the contributions of each individual activity proposed within the research design well integrated with the aims of the project? Are the coordination and synergy within the project adequate to ensure the achievement of its central objectives?

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

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

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

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

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

Not Applicable

Not Applicable

Not Applicable

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

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Allergy and Infectious Diseases, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA . Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 

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

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

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

• Organizing, attending and serving as the Chair of one of the Annual Programmatic Meetings of all awards funded under this FOA, starting in the second year of award; these meetings and their organization will rotate among the awards sites on an annual basis. The programmatic kick-off meeting will be held soon after award and will be organized by the NIAID Project Scientist in coordination with all funded awards.
• Organizing and hosting annual site visit activities.
• Advertising the availability of the project’s generated resources through outreach activities.
• Ensuring that results obtained from the research project are analyzed, published and communicated to NIAID in a timely manner, so that an up-to-date summary of program accomplishments can be maintained.
• Providing suggestions for members of the Steering Committee soon after award.
• Participating in the activities of the Steering Committee as needed and following the policies and procedures developed by the Steering Committee.
• Providing semi-annual progress reports to report primarily on scientific progress. The format and maximum number of pages will be defined by the NIAID after award.
• Ensuring that all projects involving human or animal subjects have the appropriate clearances (e.g., IRB, FWA, IACUC, human subject s research training, and other required documentation) during the entire award period.
• Keeping NIAID staff apprised of any potential impediments to execution of the goals of the project.
• Agreeing to be active participants in collaborative activities among all projects funded under the NIAID Systems Biology for Infectious Diseases Research initiative. Collaborative activities may include attending teleconferences and meetings focused on common scientific interests and issues. The multi-disciplinary and collaborative nature of the projects funded under the NIAID Systems Biology initiative creates an extraordinary opportunity for information exchange and scientific advancement; investigators are expected to take advantage of this opportunity by participating in both formal events established expressly for this purpose and informal investigator-initiated dialogues.
• In addition to following the NIH Genomic Data Sharing Policy, following the requirements and timelines described in the NIAID Data and Reagents Sharing and Release Guidelines (http://www.niaid.nih.gov/LabsAndResources/resources/dmid/gsc/Pages/data.aspx). Project-generated data and software should be made available through a publicly accessible project website and other publicly accessible resources, including those at the NIAID funded Bioinformatics Resource Centers (http://www.niaid.nih.gov/dmid/genomes/brc/default.htm), at NCBI (http://www.ncbi.nlm.nih.gov/) and/or other repositories to be determined. Program-generated data and software include, for example:
• all research data (both experimentally and computationally generated) and associated metadata;
• database schema and specifications;
• experimental protocols and Standard Operating Procedures (SOPs); and
• data analysis tools, models and algorithms generated under this contract, including model parameters and source code, complete use documentation and tutorials.

Whenever possible, the awardee shall provide software certified by the Open Source Initiative (http://www.opensource.org/licenses/), to guarantee the right of others to read, redistribute, modify, and freely use the software.

Program-generated novel reagents (e.g., expression vectors, mutant strains, libraries, protein clones), should be made available upon request or through NIAID-supported repositories, such as the NIAID BEI Resources (http://www.beiresources.org/) or in other repositories to be determined.

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 role of the NIAID/NIH Project Scientist in the cooperative agreement is to support and encourage the recipient's activities by substantial involvement as partners and facilitators in the process without assuming responsibilities that remain with the PD(s)/PI(s).
• The NIAID Project Scientist will work closely with the PD(s)/PI(s) and other project scientists to facilitate collaborations and to leverage the NIAID resources available.
• The NIAID Project Scientist will monitor the progress of the awarded projects, help coordinate research approaches, and contribute to the shaping of research projects or approaches as warranted.  The NIAID Project Scientist will support and facilitate this process but will not direct it.
• The NIAID Project Scientist will keep the project informed about other ongoing studies supported by NIAID to avoid duplication of effort and encourage sharing/collaboration in infectious diseases research. 
• The NIAID Project Scientist will serve as a non-voting member of the Steering Committee and will assist in developing the operating guidelines and consistent policies for dealing with situations that require coordinated action.
• The NIAID Project Scientist will retain the option to recommend the withholding or reduction of support from any cooperative agreement that substantially fails to achieve its goals according to the milestones agreed to at the time of the award or fails to comply with the Terms and Conditions of the award.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

The NIAID Project Scientist will provide overall coordination across all funded awards, and will coordinate with the PD(s)/PI(s) to facilitate the achievement of program goals.  In the event that some members of the funded projects develop common research interests, working groups may be formed to pursue collaborative activities.

In addition, PD(s)/PI(s) and the NIAID Project Scientist will participate in the Steering Committee activities as needed. 

Steering Committee:

A Steering Committee will be established by the NIAID in collaboration with the awardees to review the progress in meeting the goals of all projects funded under this RFA and of the Systems Biology for Infectious Diseases Research initiative. The Steering Committee will also make recommendations for the continuation or re-direction of the funded projects on an ongoing basis and in consultation with the NIAID staff. The NIAID may re-budget individual U01 funds based on recommendations of the Steering Committee.

The PD(s)/PI(s) of the awarded programs will provide NIAID with suggestions for members of the Steering Committee soon after award. The Steering Committee is expected to consist of approximately 10 individuals who are not key personnel or collaborators of the key personnel of any of the awards.

The Steering Committee will prepare concise (3-4 pages) summaries of the Steering Committee meetings which will be delivered to members of the group and NIAID soon after each meeting. The Committee will meet on an annual basis in conjunction with the Annual Programmatic Meetings and on ad-hoc basis by conference calls, as needed. Committee’s meetings will include NIAID staff, and may include PD(s)/PI(s) and other members of the funded projects as necessary.

The Steering Committee will select one member to be the Chair of the Committee and the Chair will not be a NIAID staff member.

The Steering Committee will meet at least once per year in Rockville, Maryland or in another location in the U.S. to be specified.

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 Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: GrantsInfo@nih.gov

Maria Giovanni, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-496-1884
Email: mgiovanni@niaid.nih.gov

Eleazar Cohen, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5881
Email: ecohen@niaid.nih.gov

Jason Lundgren
National Institute of Allergy & Infectious Diseases (NIAID)
Telephone: 240-669-2973
Email: Jason.Lundgren@nih.gov

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.