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Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute of Environmental Health Sciences (NIEHS)

National Cancer Institute (NCI)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Funding Opportunity Title
Identification and Characterization of Bioactive Microbial Metabolites for Advancing Research on Microbe-Diet-Host Interactions (R01 Clinical Trial Not Allowed)
Activity Code

R01 Research Project Grant

Announcement Type
New
Related Notices

  • August 3, 2021 - Notice of NICHD Participation in PAR-21-253 . See Notice NOT-HD-21-041.

Funding Opportunity Announcement (FOA) Number
PAR-21-253
Companion Funding Opportunity
RFA-DK-21-014 , U24 Resource-Related Research Project (Cooperative Agreements)
Assistance Listing Number(s)
93.847, 93.121, 93.113, 93.393, 93.396, 93.855
Funding Opportunity Purpose

The purpose of the Funding Opportunity Announcement is to invite applications to identify and characterize microbial metabolites that will establish causal associations between microbial metabolism and host health and disease. Data acquired through this initiative will be used to create a knowledgebase of microbial metabolites and associated functions that will be provided to the research community. Development of the database and knowledge portal for these awards will be supported under a separate initiative: RFA-DK-21-014, Identification and Characterization of Bioactive Microbial Metabolites for Advancing Research on Microbe-Diet-Host Interactions Knowledgebase Management Center (Clinical Trial Not Allowed).

Key Dates

Posted Date
July 06, 2021
Open Date (Earliest Submission Date)
September 20, 2021
Letter of Intent Due Date(s)

September 20, 2021; May 20, 2022; September 20, 2022; May 19, 2023 and September 19, 2023

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
October 20, 2021 October 20, 2021 Not Applicable March 2022 May 2022 July 2022
June 22, 2022 June 22, 2022 Not Applicable November 2022 January 2023 April 2023
October 20, 2022 October 20, 2022 Not Applicable March 2023 May 2023 July 2023
June 22, 2023 June 22, 2023 Not Applicable November 2023 January 2024 April 2024
October 19, 2023 October 19, 2023 Not Applicable March 2024 May 2024 July 2024

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date
October 20, 2023
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Accumulating evidence suggests that microbes and their metabolites play a critical role in host physiology and impact the pathophysiology of diseases including infectious, inflammatory, and metabolic diseases, and cancer. The microbiota metabolizes dietary components, antibiotics and other xenobiotics to a variety of bioactive metabolites that may influence host metabolic pathways and pathophysiology. In order to establish causal associations between the gut microbiota and host metabolism and to guide targeted precision nutrition and precision medicine approaches, it is crucial to understand the entire spectrum of possible microbial metabolites and their biological relevance to host physiology. Several biologically relevant metabolites have been recently identified and catalogued (DOI:10.1126/science.1254766; DOI:10.1016/j.tips.2019.04.006). However, a vast majority of microbial metabolites remain unknown, impeding the progress in the advancement of microbiome research and for the characterization of host microbiome interactions.

Recent scientific advances in the microbiome field have arisen from combining metabolomics technologies with metagenomics, meta-transcriptomics, biosynthetic candidate Bacterial Gene Clustering approaches to identify and characterize microbially derived metabolites. Other advances in model systems to interrogate the function of identified metabolites including artificial gut simulators, organoids, and humanized mouse models along with in silico and synthetic biology approaches further enable characterization of microbial metabolites. The current FOA invites applications that employ combinations of recent and novel innovations and resources for identifying, characterizing and determining the function of microbial metabolites, including circulating microbial metabolites, beyond what is already known. The applicants may include well-characterized microbial metabolites (e.g., short chain fatty acids, bile salts, amino acid metabolites, vitamins and antimicrobials), but the emphasis should be on the identification and characterization of novel and less well understood metabolites. Applicants are encouraged to build on observations of known bioactive microbial metabolites, which will serve as the basis for the further identification and characterization in any proposed new studies. The current FOA is focused on hypothesis-generation and does not support clinical trials, or studies that functionally characterize only previously identified candidate metabolites.

Research objectives that could be supported include but are not limited to:

  1. Determination of the molecular identity of novel gut microbial metabolites, including circulating microbial metabolites in relevant human biological samples.
  2. Identification and characterization of the source of microbial metabolites, (including dietary, drug, or other endogenous or environmental sources); the characterization may encompass the microbial taxa or consortia involved, and the bacterial genes and enzymatic pathways leading to their production.
  3. Initial characterization of biological function and translational relevance of the identified metabolites:
    1. Using appropriate systems such as in silico, In vitro, ex-vivo organoids, artificial gut simulators such as Artificial gut, microfluidics-based Human Microbiome Coculture systems, humanized animal models, Bacterial Gene Clusters analysis; and/or
    2. Technology development of appropriate methods or models for analyzing these metabolite s in biological samples.

Data sharing and Creation of Knowledgebase: One of the main objectives of the FOA is to provide data that will be needed to develop a knowledgebase that is readily accessible by the research community. A Knowledgebase Management Center (KMC) supported by a cooperative agreeement mechanism and U24 activity code, via RFA-DK-21-014: Identification and Characterization of Bioactive Microbial Metabolites for Advancing Research on Microbe-Diet-Host Interactions Knowledgebase Management Center (U24 Clinical Trial Not Allowed) will coordinate the activities of these sites for developing common data elements and formats for the creation of the knowledgebase. The resultant database will serve as a resource for the research community to stimulate additional research studies. In addition, the KMC will also support minimal tool development for enabling and facilitating data analysis of data contained within the knowledgebase and for improving the operations of the database.

Successful grantees will participate in activities organized by the KMC such as conference calls and other meetings, for the purposes of enhancing creation of the knowledgebase, developing necessary data pipelines, curation and harmonization strategies. The grantees will assist and advise the KMC in determining the analytical tools needed for analyzing the data and for enhancing the utility of the knowledgebase. In addition, grantees will also agree to deposit the data generated by their sites in the KMC, for the purposes of sharing the data widely with the research community. They will also agree to share the data among the grantees funded under this FOA for the purposes of knowledge exchange. Grantees will also agree to attend one annual in-person meeting organized by the KMC.

Applicants are strongly encouraged to pay close attention to specific IC interests for research examples provided below:

NIDDK is interested in human studies that address the microbiome and its metabolites in response to a variety of dietary interventions; in digestive and metabolic diseases including diabetes and obesity.NIDDK is also interested in studies that explore the microbiome and its metabolites in gestational diabetes (and risk of gestation diabetes) that impact the health of pregnant mothers.

NICHD is interested in human studies that address the microbiome and its metabolites in infants who are born preterm or at low birthweights; in child growth and development; in relation to diet and/or nutritional status of children, pregnant individuals or lactating individuals. Additionally, NICHD is interested in the microbiome and its metabolites in gestational diabetes (and risk of gestation diabetes) on pregnancy outcomes and fetal outcomes.

NIDCR will consider applications for this FOA within the above listed scope only if they pertain to the microbiota of the human oral cavity (specifically those microbial communities composed of oral health related archaea, bacteria, fungi and viruses). Specific interest areas include the role of metabolites produced by the oral microbiota in: Maintenance of a healthy oral environment; Dysbiosis and disease of the oral cavity; Host interactions and modulation of host metabolism; Commensal and/or pathogenic bacterial interspecies interactions; and Interactions affecting the interface between tooth and restorative materials.

NCI is primarily interested in understanding the relationship between the gut/oral microbiome and cancer development. Several gut microbial-derived metabolites have been identified for their contribution to cancer prevention, risk, development and progression. Microbial metabolites may also influence cancer treatment response and symptom management. The pro-tumorigenic effects of enterotoxigenic Bacteroides fragilis, colibactin-producing Escherichia coli and Fusobacteria are thought to occur through the production of toxins and oncometabolites that affect oncogenic signaling pathways. In contrast, the biological effects of microbial metabolites generated from dietary components such as tryptophan metabolites and short-chain fatty acids may be cancer preventive. For example, short chain fatty acids have been observed to regulate inflammatory responses, intestinal barrier function, oxidative stress and carcinogenesis in preclinical models. NCI is interested in research aimed at identifying and characterizing additional/novel diet-microbial derived metabolites that influence cancer processes throughout the cancer spectrum. The rationale for selecting clinical studies and biological samples for discovery of novel metabolites should be grounded in sound epidemiologic and biologic evidence. NCI is also interested in supporting applications that explore the biological function and molecular mechanisms of these novel microbial metabolites.

Examples of responsive research applications include, but are not limited to:

  • What is the influence of specific dietary components or dietary patterns on the metabolic output from the microbiome? By what mechanism(s) do these metabolite signals promote or inhibit carcinogenesis? (stromal changes, systemic inflammation)?
  • What are the critical cell pathways impacted by microbial metabolite interactions? How are these metabolite signals sensed and transported by tumor cells and tumor stromal components?
  • Does microbial metabolic output or requirements for micronutrients (polyamines) and trace elements (e.g.iron) influence tumor development and metastasis?
  • Can tumor or tumor stroma cell (adipocyte, fibroblast, immune) functions and metabolism be manipulated through dietary/metabolite interventions?
  • Can drug or diet induced alterations of microbial metabolic output prevent the production of tumor promoting oncometabolites (or enhance the production of protective metabolites)?
  • What metabolic interactions influence (tumor promoting) biofilm establishment in the GI tract?
  • What novel analytical tools or models are needed to study the real-time metabolic activity of both hosts and their microbiomes in clinical and preclinical nutrition research?

NIEHS will consider applications for this FOA within the above listed scope if they include consideration of microbial metabolites that are derived from exposure to environmental chemicals, or those that interact with environmental chemicals inside the host. Environmental factors of interest are: chemicals that people are exposed to via air, water, or food, including air pollutants, pesticides, metals, industrial chemicals, nanomaterials, or environmental tobacco smoke.

NIAID conducts and supports basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. The myriad microbial metabolites produced by the microbiota influence resistance to infectious and immune-mediated diseases, host response to infection, immune system development, and response to radiation injuries. Identification of these metabolites and the bacteria that produce them may provide the mechanistic insight needed to translate this knowledge into effective therapeutics and novel prophylactics for infectious, immunologic, or allergic diseases, or radiation injuries. NIAID therefore encourages collaboration between scientists studying the human microbiome and infectious disease experts and/or immunologists and/or radiation biologists on the identification and characterization of bioactive, microbial-derived metabolites for their translational potential to improve human health.
Examples of responsive research include, but are not limited to:

  • Interrogations of known or novel microbial metabolites, and their sources, in support of translational science and mechanism of action studies for novel therapeutics (e.g., live biotherapeutic products), or prophylactic approaches (e.g., vaccines) for the treatment and prevention of infectious and immune-mediated diseases or promotion of tolerance to allergens, autoantigens, or allogeneic transplants.
  • Basic and translational research to identify and characterize microbial metabolites that directly impact microbial viability, pathogen invasion (e.g., antimicrobials) or otherwise modify aspects of the pathogen physiology towards a virulent (toxin expression, invasion, etc.) or avirulent state (i.e., persistence).
  • Studies seeking to characterize and quantify novel or known metabolites, and their sources, to better understand infectious diseases, host immune response to infection, immune system development, and immunological diseases (e.g., allergies, autoimmunity, or immunological rejection of transplanted organs, pancreatic islets, or vascularized composite allografts), and/or radiation injuries.
  • Studies to determine how microbial metabolites influence immune cell differentiation, immune function and immunopathogenesis in the setting of human autoimmune and allergic disease.
  • Studies to determine how the overall microbial metabolite profile, as well as individual metabolites, influence the balance between immune tolerance and immune response.
  • Studies to identify novel microbial metabolites and metabolite profiles associated with human autoimmune and allergic diseases.

Applications Not Responsive to this FOA

Applications that do not address one of the diseases described by the above ICs will not be considered responsive to this FOA. Applications proposing only identification or characterization of microbial metabolites will also be considered non-responsive. Applications that are unwilling to to work with the Knowledgebase Management Center or deposit the data in the KMC will be considered non-responsive. Non-responsive applications for this FOA will be withdrawn without review.

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

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Resubmission - Resubmission applications from this FOA, PAR-21-253: Identification and Characterization of Bioactive Microbial Metabolites for Advancing Research on Microbe-Diet-Host Interactions (R01 Clinical Trial Not Allowed)

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are not limited, but need to reflect the actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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)

Local 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)

Federal Governments

  • 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
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Required Registrations

Applicant organizations

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

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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)2.

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) 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.

Letter of Intent

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:

Padma Maruvada, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8884
Email: maruvadp@mail.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments: Willingness to work with the KMC: Please entitle this attachment "Willingness to Participate" and include a statement indicating a willingness to:

  • Work with KMC to develop and comply with data sharing policies;
  • Work with KMC to develop the data formats and templates;
  • Deposit the data in the KMC database using the data formats and templates as agreed with the KMC, in a timely manner as per the data sharing policy;
  • Attend the annual meeting organized by the KMC; and
  • Participate in monthly conference calls and other meetings as organized by the KMC for the purpose of data sharing.
SF424(R&R) Senior/Key Person Profile

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

The applicants should have demonstrated expertise in microbiome and/or metabolomics research and should  have reasonable experience in conducting studies for identifying and characterizing microbial metabolites.

R&R or Modular Budget

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

All the key personnel including the PD/PI should allocate appropriate effort and time commitment for the project. Applicants should budget for traveling the PD/PI and other essential members to attend one in-person annual meeting in Bethesda, MD region, organized by the KMC.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy: The Research Strategy should include a detailed description of the analytical pipelines for identifying microbial metabolites along with appropriate quality control measures. The plan will also describe detailed strategies for characterizing the microbial metabolites. In addition to identification and characterization of microbial metabolites, the data acquired from these projects will be compiled into a knowledgebase. A Knowledgebase Management Center (KMC) supported by RFA-DK-21-014 will facilitate the knowledgebase development and related activities. Accordingly, applicants should provide a detailed description on how they will work with the KMC in developing data sharing plans, identifying appropriate data formats/templates. Applicants should also describe the plans for participating in conference calls, meetings and other activities as organized by the KMC. They are also expected to attend one annual in-person meeting in the Bethesda, MD area organized by the KMC.

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.

The following modifications also apply:

  • Applicants are expected to provide a detailed Data Sharing Plan, for the purposes of the creation of knowledgebase. The applicants should be willing to advise the KMC for developing bioinformatics tools for analyzing the data from the knowledgebase. The applicants should also agree to deposit the data generated by their sites, for the purposes of developing and sharing the knowledgebase widely with the research community.

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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

Important reminders:

All PD(s)/PI(s) 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.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Use of Common Data Elements in NIH-funded Research
Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (https://cde.nlm.nih.gov/home/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

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).

Scored Review Criteria

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? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: Will the generated data advance our knowledge about the microbial metabolites? Do the approaches chosen for high resolution analysis allow for the discovery of novel metabolites? Are the microbial metabolites chosen for high-throughput studies well justified? Will the tools and data to be generated be useful for the community?

Investigator(s)

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

Specific to this FOA: Is there demonstrated evidence that the investigators have experience working collaboratively? Will the investigators be able to contribute to the creation of knowledgebase on microbial metabolites? Do the investigators have appropriate experience and training to carry out the proposed project and to contribute appropriately to the KMC?

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? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

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

Specific to this FOA: Does the application propose analytical approaches/pipelines appropriate for identifying a broad range of novel microbial metabolites? Is there an overall strategy to characterize novel microbial metabolites? Are the models chosen for interrogation well thought out for characterizing microbial metabolites and do they take advantage of state- of- the art methods?

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?

Additional Review Criteria

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.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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.

Applications from Foreign Organizations

Not Applicable

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 the inclusion and adequacy of the Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS)

Authentication of Key Biological and/or Chemical Resources:

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

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review (CSR), 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 will receive a written critique.

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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

2. Administrative and National Policy Requirements

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

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

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

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

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

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Padma Maruvada
National Institute of Diabetes, and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8884
Email: maruvadp@mail.nih.gov

Tamara McNealy
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-2732
Email: tamara.mcnealy@nih.gov

Sharon A. Ross
National Cancer Institute (NCI)
Telephone: 240-276-7124
Email: rosssha@mail.nih.gov
 

Anika Lin Dzierlenga
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3125
Email: dzierlengaal@mail.nih.gov

Tamara Lyn McNealy, PhD
National Institute Of Dental & Craniofacial Research (NIDCR)
Phone: 301-827-2372
E-mail: tamara.mcnealy@nih.gov

Sharon A Ross
National Cancer Institute (NCI)
Phone: (240) 276-7124
E-mail: rosssha@mail.nih.gov

Phillip J Daschner
National Cancer Institute (NCI)
Phone: 240-276-6190
E-mail: pd93u@nih.gov

Ryan Ranallo, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3351
Email: ryan.ranallo@nih.gov

Anika Lin Dzierlenga
National Institute Of Environmental Health Sciences (NIEHS)
Phone: 984-287-3125
E-mail: anika.dzierlenga@nih.gov

Ashley J, Vargas, PhD, MPH, RDN
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-827-6030
Email:ashley.vargas@nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Sharon Bourque
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-888-8846
Email: bourques@mail.nih.gov

Diana Rutberg, MBA
National Institute Of Dental & Craniofacial Research (NIDCR)
Phone: (301) 594-4798
E-mail: rutbergd@mail.nih.gov

Amy R Bartosch
National Cancer Institute (NCI)
Phone: 240-276-6375
E-mail: amy.bartosch@nih.gov

Dhana Khurana
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone:  240-669-2966
Email: vandhana.khurana@nih.gov

Jenny L Greer
National Institute Of Environmental Health Sciences (NIEHS)
Phone: 984.287.3332
E-mail: jenny.greer@nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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


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