Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). The FOA will be administered by the National Institute for Dental and Craniofacial Research (NIDCR, http://www.nidcr.nih.gov/) on behalf of the NIH.
Funding Opportunity Title	Evaluation of Multi- omic Data in Understanding the Human Microbiome’s Role in Health and Disease (U54)
Activity Code	U54 Specialized Center- Cooperative Agreements
Announcement Type	New
Related Notices	December 20, 2012 - See Notice NOT-RM-13-004. Notice Announcing Frequently Asked Question (FAQs), Applicant Information Webinar, and Human Subjects Information for this RFA.
Funding Opportunity Announcement (FOA) Number	RFA-RM-12-021
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.310
Funding Opportunity Purpose	This FOA invites applications for projects that will: 1. generate microbiome taxonomic, metagenomic and functional data from clinical biospecimens obtained from a cohort(s) of carefully-phenotyped subjects with a specific disease or health state; and 2. combine the microbiome and host data to produce a community resource. This program is a component of the NIH Common Fund Human Microbiome Project (http://commonfund.nih.gov/hmp/).

Posted Date	November 30, 2012
Letter of Intent Due Date(s)	January 8, 2013
Application Due Date(s)	February 8, 2013
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	May/June, 2013
Advisory Council Review	August, 2013
Earliest Start Date	September, 2013
Expiration Date	February 9, 2013
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS 398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Overview

This initiative is funded through the NIH Common Fund in the NIH Office of the Director's Office of Strategic Coordination, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

The goal of this FOA is to generate exploratory dataset(s) from microbiomes of well-phenotyped subjects in order to create a combined dataset of microbiome and host properties as a community resource. The long-term objective of this activity is for the community to be able to utilize this combined dataset to explore whether study of the human microbiome beyond sequenced-based analyses will yield important new insights in understanding human health and disease. This FOA invites applications that propose to produce taxonomic, metagenomic and functional human microbiome data i.e., 'omic data: microbiome transcriptomic, proteomic, and metabolomic data - from a human cohort study of a specific health state or disease condition, and to create a combined dataset of these data. Given the 3-year period of the initiative, it is anticipated that the awardee(s) will not have sufficient time to completely evaluate the dataset. However, applicants are asked to propose a proof-of-principle test of the dataset in order to evaluate the useability of the dataset for testing hypotheses about the role of the microbiome in health and disease.

Background

The two goals of the first phase of the NIH Common Fund Human Microbiome Project (HMP, http://www.commonfund.nih.gov/hmp, 2008-2012) were to determine whether study of the human microbiome at the metagenomic level (1) would identify a core microbiome associated with specific health or disease states and (2) correlates specific disruptions of the microbiome with the presence of certain diseases. To study these questions the HMP analyzed correlations between human health and/or specific diseases, and the taxonomic and genetic composition of the microbiome. The preliminary results from this phase demonstrated (1) that it is feasible to use metagenomics as an approach to study the taxonomic and genetic composition of the microbiome, and (2) that the taxonomic composition of an individual s microbiome (i.e., diversity and relative abundance of microbial members) differs so significantly from the microbiome of another individual's with a similar health status that taxonomic characterization alone, in some cases, may not be sufficient to reveal correlations between the microbiome in specific health conditions and disease states. Interestingly, in silico metabolic pathway reconstructions of the metagenomic data from the HMP healthy cohort study suggested that the microbiomes of healthy subjects may share similarities in their metabolic pathways and that this may be indicative of a core property of this health state. Further, in some of the HMP Demonstration Projects, which were designed to evaluate the association of microbiomes with specific diseases (http://www.hmpdacc.org/impacts_health/impact_health.php), analysis of microbiome properties beyond metagenomics, such as of transcripts or proteins or metabolites, suggested losses or gains of important microbiome functions associated with some disease states. These new insights into microbiome properties were not apparent from an analysis of the microbial taxonomic composition alone. Additional information about the HMP and its datasets and research products can be found at these websites (http://www.commonfund.nih.gov/hmp; http://www.hmpdacc.org).

Collectively, these studies suggest that it may be important to consider microbiome functional properties when evaluating the role of the microbiome in human health and disease. However, data are needed to enable development of the necessary computational tools and analytic approaches to study microbiome functional properties and to enable analysis of combined datasets of microbiome and host properties. The long-term objective of this program is to generate the necessary test data for the future development of tools and analytic approaches to study the associations of microbiome functions with host phenotypes. Once this type of working dataset is made available, tools and analytic development can occur through either activities already underway in the NIH Institutes/Centers (ICs) or may be supported through future IC-specific program announcements or targeted FOAs.

Purpose

The purpose of this second phase of HMP is to create a community resource that can be used to decipher the role of the microbiome in human health through (1) acquisition of multi omic types of data from a well-phenotyped human cohort study(s), (2) defining practices for sample collection that support multi-omic analyses, (3) making these data available to the broad community through, as needed, appropriate controlled access databases for qualified researchers, and (4) improving upon all of these methods and protocols. These goals will be achieved by funding up to two exploratory projects to generate and integrate a combined set of microbiome taxonomic, metagenomic and functional property data with host phenotype data of samples collected from human donors. The dataset will include multiple microbiome omic data types, including taxonomic composition and at least three of four other omic data types, such as metagenomic, metatranscriptomic, metaproteomic and metabolomic data. These data will be combined into one dataset and will be rapidly released to the research community, as needed through controlled access databases open to qualified researchers, so the community can participate in the analysis of the combined dataset.

The requirements called for in this FOA are complex and it is expected that applicants likely will need to form collaborations with other groups that have the required bioinformatics expertise, the clinical biospecimens or the ability to consent subjects to obtain the appropriate biospecimens and the clinical data as well as the analytical facilities. The partners in such a HMP Collaborative Center should have the necessary capabilities to complete the sample and data gathering, data integration and data deposition in the three-year project period. Because of the 3-year time line of this initiative, the facility(ies) which will produce the data to measure the proposed microbiome properties will need to be ready to embark on the project with little or no scale up time.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New The OER Glossary and the PHS 398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The NIH Division of Program Coordination, Planning and Strategic Initiatives, Office of Strategic Coordination intends to fund 1 or 2 awards, committing a total of up to $5,000,000 in FY 2013.
Award Budget	Applications may request up to $3.0 million per year (total costs).
Award Project Period	Applications may request a project period of up to 3 years.

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

Higher Education Institutions

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

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

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• 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)
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations must complete the following registrations as described in the PHS 398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• System for Award Management (SAM) must maintain an active entity registration (formerly CCR registration), to be renewed at least annually. Use the Sam.gov Manage Entity function to manage your entity registrations. See the Grants Registration User Guide at SAM.gov for additional information.
• eRA Commons

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

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least6 weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(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 PHS 398 Application Guide.

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

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for 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 are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS 398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

• Descriptive title of proposed research
• Name(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:

Yasaman Shirazi, Ph.D.
Chief, Scientific Review Branch
National Institute of Dental and Craniofacial Research
National Institutes of Health
6701 Democracy Blvd.
Room 622
Bethesda, MD 20892 (U.S. Postal Service Express or regular mail)

Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-594-5593
Fax: 301-480-8303
Email: yasaman.shirazi@nih.gov

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

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

At the time of submission, three additional paper copies of the application and, if applicable, three electronic copies of the Appendix files (on CD) must be sent to:

Yasaman Shirazi, Ph.D.
Chief, Scientific Review Branch
National Institute of Dental and Craniofacial Research
National Institutes of Health
6701 Democracy Blvd.
Room 622
Bethesda, MD 20892 (U.S. Postal Service Express or regular mail)

Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-594-5593
Fax: 301-480-8303
Email: yasaman.shirazi@nih.gov

All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed, with the following exception or additional requirement:

• The Research Strategy is limited to 30 pages.

The applicant can select any type of Center structure that will best address the goals of the FOA. It is expected that the HMP Collaborative Center will include a variety of Components, such as administrative, data coordinating and computational/bioinformatics/statistical cores, clinical sites and/or analytical laboratories (genomics, proteomics, metabolomics, etc.). Regardless of the proposed structure, the applicant must present a clear organization of the different Components and a rationale for this structure.

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Face page for the Center; name of the PD/PI for the Center; Multiple PD/PIs may be proposed.

Provide a succinct description of the Center, addressing the key aspects of the scientific scope and administrative structure.

Project/Performance Sites. List the performance sites where the research will be conducted.

Senior/Key Personnel. List the PD/PI of the Center, followed by the leaders of the key components and then other key personnel and then other significant contributors.

Do not repeat biosketches if an individual has multiple roles. Potential members of any Advisory or Steering Committees must not be contacted or named in the application. However, the expertise required for these positions should be described.

Do not use Form Page 3 of the PHS 398; a more comprehensive Table of Contents (TOC) is needed for this Center. Bearing in mind that the application may be scientifically reviewed in sections based upon the proposed structure of the HMP Collaborative Center, prepare a detailed TOC that will enable reviewers to readily locate specific information pertinent to the overall application as well as to any proposed Components of the Center. Applicants must define a clear structure for the Center to aid in the review and evaluation of the application. These Components may include administrative, data coordinating, computational/informatics/statistical cores, clinical sites, and/or laboratories (genomics, proteomics, metabolomics, etc.). Further, each Component should be identified by name and responsible Component Director. The page location of the overall budget should be indicated in the TOC.

The Center budget should include the overall budget as well as any details about the budget for the Components. Budget justifications should be included. Major equipment costs will be allowed, if well justified.

Biographical sketches of all personnel for all Components of the Center should be included with the PD/PI first, followed by those of other key personnel in alphabetical order.

For the Center, resources may include laboratory facilities, equipment, and services. Depending of the proposed structure, describe in detail the resource(s) that will part of each Component, and how it will add to the Center.

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims

The Specific Aims should describe the overall goals and structure of the HMP Collaborative Center.

Research Strategy

The organization suggested below is optional and the applicant is free to use an alternative presentation but, in so doing, must address all of the issues raised below.

Background and Preliminary Data. This section should include the following:

• General introduction and justification. Applicants should present information about past work related to the goals of this FOA. If the applicant has participated as part of a collaborative research group, efforts to facilitate the success of that larger group should be described.
• Progress Report. Applicants should describe their track record in studying the system proposed and in utilizing the proposed methodologies. The application should provide detailed information about throughput, quality, and cost for past performance. If large-scale, high throughput technologies are proposed, then a concise description of past experience with these technologies is required. The application should describe the experience of the applicant and/or the collaborators from the different Components with the proposed tools or in tool development relevant to the data types to be analyzed. The description should also include past experience in the approaches proposed for the incorporation of different data types into a combined data set.

Rationale. The rationale for the choice of the human body site microbiome to be studied with respect to the proposed disease or health state must be addressed. In addition, the following areas should be addressed:

• Describe the biological system in which the relationship between the microbiome and health/disease will be studied.
• Justify which features of the proposed specific disease or health state make it of general use and interest to the broad research community for the study of the microbiome and disease or health.
• Describe clearly the health or disease state and phenotypes to be examined, why the cohort was chosen, and the rationale for the primary host phenotype(s) that were used as the criteria for selection of the clinical biospecimen donors from the cohort.
• Justify why additional microbiome data beyond microbial taxonomic composition are needed in order to expand our understanding of the microbiome’s role in the specific disease or health state under study.
• Justify what types of microbiome functional data will be collected, why these data need to be collected for the health or disease condition under study, what methods are proposed for collecting these data and why these methods were chosen for the study.

The rationale for the approach used for incorporating the different data types into one combined dataset for access and use by the broader community must be addressed. In addition, the following areas should be addressed:

• Describe the interface which will be adopted or developed to incorporate or link the different data types and whether the data will be archived in different databases or in one database.
• If in different databases, describe how the data will be incorporated into a framework which will allow the community to query the data across the different databases.
• Describe the interface which will be adopted or developed to incorporate or link the microbiome data types with the human clinical phenotype, the human subject sequence data or any other restricted data in dbGaP or other controlled access database.
• Describe the type of derived data planned for each of the data types which will be the data that is used for the combined dataset.
• Describe how the combined dataset will allow each of the data types to be queried independently and how the combined dataset will be queried.
• Any results from an analysis which includes the controlled access data retain their controlled access status. Describe what provisions will be made for results which emerge from an analysis that includes controlled access data to be archived in a controlled access database(s).
• Describe the existing IT infrastructure or tracking technologies that will be used to create the combined dataset.
• Describe the proposed proof-of-principle test that will be used to evaluate the useability of the combined dataset and whether it can be queried by the broader community to address health or disease related hypotheses.
• Describe the database(s) where the data will be deposited and how the database will provide controlled access and what procedure will be adopted or developed to allow only qualified researchers from the broader community to request and gain access to the controlled access data.

Overall Center Structure, Governance and Management. The applicant can select any type of Center structure that will best address the goals of the FOA. Regardless of the proposed structure, the applicant must present a clear organization of the different Components and a rationale for this structure. There should also be inclusion of clear governance and management strategies. The Center may include members from more than one institution. As these are cooperative agreements, the governance and management of these Centers are discussed below in the Cooperative Agreements section under Terms and Conditions of the award. In particular, the following should be addressed:

• Describe clearly the proposed organizational structure, communication strategies and succession plans.
• Address the bioinformatics and data management and data sharing strategies as part of the organizational structure.

Sample Choice and Collection. Applicants should propose to collect a carefully defined set of clinical biospecimens, and phenotype data, from one or more body sites, along with additional host tissues or biofluids, as appropriate and well-justified in the application. Particular attention should be given to sample collection protocols which support analysis of microbiome properties. In addition, the application should fully address:

• The number of donors needed based on previous microbiome studies, if this information is available.
• The primary phenotypes that form the basis for any power analyses and sample size calculations. Other phenotypes and outcomes should also be described.
• The inclusion and exclusion criteria for the subjects in the cohort.
• The Standard Operating Procedures (SOPs) for sample collection from the designated body region(s) and sites must be described, including a design for collection of metadata (e.g., host characteristics, relevant environmental measurements), and a plan to ensure correct sample tracking, storage and management. The application must set out clear sampling plans with a timetable for implementation for the plan.

Sample Analyses and Data Production. Applicants can choose to use any of the appropriate current robust technologies to collect microbiome taxonomic composition data and a minimum of three of the four microbiome 'omic data types, namely metagenomics, metatranscriptomics, metaproteomics and metabolomics. In addition, because some of the methodologies can simultaneously yield a combination of both microbiome and host data, specific host genomic and host functional (transcriptome, proteome and metabolome or other) data may also be generated and added to the combined data set, if well justified in the application. If included, these human subject data should be stored in controlled access databases. The application should address the following areas:

• How the chosen technologies will be used to create data sets of sufficient quality and depth to allow analysis aimed at studying how changes in functional properties of the microbiome correlate to changes in human health or disease.
• The choice of approaches and analyses for microbiome taxonomic characterization, transcriptomics, proteomics and metabolomics must be justified and the methods well described.
• Current technical capabilities for each approach proposed and the quality of the data, the amount of data that can be anticipated from each type of sample and the current throughput capabilities of the technology in the applicants laboratories.
• Preliminary data for each methodology proposed should be included in the application. Animal model data will be permitted for this preliminary data.
• A demonstration of the ability, through computational or analytical approaches, to distinguish between host and microbiome contributions to the properties being assayed in the tissue(s) or biofluids under study.
• Several different techniques may be proposed for each microbiome data type to be generated but must be justified and well-described and with discussion of effect size, presentation of power calculations (where appropriate and available), quality control measures, and projected cost per sample for each technique. These calculations and estimates should be based on prior experience, preferably with a clinical biospecimen or animal model specimen for microbiome study, and projections of throughput expectations.
• Costs for processing of each data type should be described and provided separately from the cost for each assay type. The expected throughput for each methodology should be well described.
• Potential bottlenecks or other anticipated problems and proposed solutions should be well addressed.
• Describe a baseline quality standard. A description of how quality will be measured must be given for all methodologies. This description should include how the quality standard was developed and how quality will be measured during the project.
• Strategies to organize and standardize the microbiome data and the host clinical phenotype data so that a combined HMP test dataset(s) can be produced that is easily useable by the community should be addressed.
• For each methodology, the overall projected cost and throughput proposed for data production in each year of requested funding should be included. The description given above in the progress report (described below under the Background and Preliminary Data section) may be used to project cost, quality and throughput of the data produced by the proposed methodologies. Timelines and quantitative milestones should be given where appropriate, especially for throughput, cost and quality, of proposed methodologies.

Data Processing, Organization and Release. The application must describe strategies to utilize existing tools to process and organize the derived microbiome and phenotype data types into a combined dataset suitable for analysis by the broader community and if human subject data are included, available to only qualified researchers through a controlled access database for subsequent analysis. The application must also address:

• The proposed data snapshot or data milestone. The application should justify the stage at which an early data milestone will occur and what results can be expected from a combination of the different data into this early dataset.
• The informatics that will be used to support the data production and processing, including routine IT/systems administration, LIMS, quality assessment, etc.
• Any bioinformatic tool improvement needed for processing and combining the dataset. Because of the short timeline of this initiative, development of new tools is not included in this FOA, but improvement of existing tools may be feasible and support for tools improvement may be included in the application. If applicants choose to improve existing tools, tool improvement should be thoroughly described and justified. Descriptions of what tools will be used should also include the applicants experiences in using them, preferably with microbiome data. Applicants should also discuss the strengths and weaknesses of the tools in the context of the proposed project.
• The bioinformatics and computational approaches that will be used to carry out a proof-of-principle test of both an early set of the combined data and of the final combined dataset to evaluate the useability of the dataset by the broader community to address microbiome and health related hypotheses.
• The existing tools that will be used or improved for these proof-of-principle tests.
• As needed, the plans to engage external members of the community in this proof-of-principle analysis.

The proposed data release plans and tools should be fully described. All data generated through this initiative will be released rapidly and, if it includes human subject data, into a controlled access database(s), available to qualified researchers in the broader community. A data release policy for the data from each of the methodologies being used should be addressed. For this application, the NIAID data release policy should be followed (http://www.niaid.nih.gov/LabsAndResources/resources/dmid/gsc/Pages/data.aspx). These plans will be reviewed by NIH staff, and agreed upon with the applicant before the application is funded.

Milestones. The application must include an estimate of the timeline for initiating and completing the project to include but not be limited to:

• Consenting and/or reconsenting (if necessary) of human subjects and collection of the clinical biospecimens and clinical phenotype data for broad data sharing through a controlled access database(s) to qualified researchers;
• Generation of the multiple 'omic data types from the microbiome and from the host;
• Data processing and incorporation into a combined dataset;
• Deposition of data into appropriate archives, to also include deposition into controlled access databases of human subject phenotype, sequence and other human subject data;
• An early proof-of-principle test of an early combined dataset and a proof-of-principle test of the final combined dataset.

The Components of the HMP Collaborative Center(s) will need to be closely coordinated to accomplish the program goals within three years. The timelines should reflect this close coordination across the Components. This is a Cooperative Agreement, and so the final timeline will be negotiated at the time of the award.

Human Subjects

Identification of an appropriate cohort. Applicants must describe an existing or readily accessible set or collection of donors/samples from a human cohort study. The subjects providing the samples must be/have been consented in a manner consistent with NHGRI policies and follow NIH guidelines for genomics research, which are also applicable to microbiome research (http://www.genome.gov/27026588), so that the samples can be utilized in the analysis of microbiome genomic and functional properties. If the subjects are not already consented for broad sharing of microbiome metagenomic and functional data which includes deposition of data in open access databases, the applicant must detail the reconsent process and the timeline for completing it within the first year of the grant. The consents should note the remote but potential risk to privacy of sharing their microbiome data in open access databases. The applicants should also address how they plan to minimize risks to the subjects' privacy in the Protection to Human Subjects section of the application. Because of the 3-year period of this initiative, utilization of an existing broadly consented cohort which allows for broad sharing of the microbiome and host data is strongly encouraged. Broad sharing is desired in order to maximize community use of the combined dataset.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modifications:

1. The application for a HMP funded project must include a plan for sharing research data. The HMP strongly endorses rapid release of HMP-related data and materials. Applicants should refer to specific NIAID policy on data release (http://www.niaid.nih.gov/LabsAndResources/resources/dmid/gsc/Pages/data.aspx) for submission of all data types. Because the purpose of this FOA is to fund the generation of an exploratory combined dataset of microbiome multi 'omic data and corresponding host phenotype data, the utility of such data to the community is largely dependent on how quickly it can be deposited into public databases which include controlled access for human subject data or appropriate websites which include controlled access for the human subject data. The NIH considers this FOA to be funding community resource projects as discussed in the report Sharing Data From Large-Scale Biological Research Projects - 2003: A System of Tripartite Responsibility available at http://www.genome.gov/10506376, which deals primarily with sequence data but is applicable in principle to all data types. The general NIH data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how research data will be shared and, if human subject data, for data archived in a controlled access database(s).

2. Responses to this FOA should propose a plan for data release as quality of the data release plan will be a criterion in the review of the application. Appropriate data release plans will be made a condition of the awards made as a result of this FOA. In some cases, public databases may not be available for some of the data types generated in this project. In these cases, the applicant should describe the data release plan that may make use of appropriate controlled access websites or describe the creation of an appropriate controlled access website which can archive the data and can make the data available to the larger research community via a procedure for qualified researchers to apply for and gain access to the data. Each of the following items should be discussed separately:

• Release of cohort subject phenotype and human sequence data to a controlled access data site specified by the NIH;
• Release of the other types of data used to characterize the functional properties of the microbiome in the system being proposed for the study to include some combination of the microbiome taxonomic composition with the microbiome metagenome, transcriptome, proteome or metabolome;
• Release of clinical metadata associated with the microbiome multi 'omic data and the host clinical phenotype data to a controlled access site; and
• Release of analyses performed by the awardee. If these analyses include controlled access data then how results of these analyses will be archived in controlled access databases.

3. All applicants must include a plan for sharing research data and reagents including clones and organisms in their application. All investigators responding to this funding opportunity should include a description of how final research data, including the derived combined test data set, will be shared with the broader research community, if needed, through the use of controlled access databases.

NIH staff will review the Data Sharing and Release Plan prior to making the award. The Data Sharing and Release Plan will also be a part of the review of the application.

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS 398 Application Guide.

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

This initiative is not subject to intergovernmental review.

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

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

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

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

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

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

Reviewers will provide an overall impact 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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Is there a high likelihood that the proposed effort can produce a novel and useful set of microbiome taxonomic, metagenomic and/or functional property data? Is there a high likelihood that the broader community will be able to use this combined dataset for analyses? Is there a high likelihood that analysis of these data will provide important information pertinent to understanding the role of the microbiome to human health and disease?

Investigator(s)

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? Do the members of the investigative team show evidence of previous successful collaborations?

If new collaborations are proposed, are the plans adequate to ensure a productive collaboration? Is the commitment of all individuals appropriate? Do the research team members have proven track records in generating, analyzing and releasing high throughput data? Do the members of the collaboration show demonstrated ability to work together in consortia?

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

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

• Does the applicant include language in the consent that informs the subjects of the remote but potential risk to privacy of data which is in open access?
• Has the applicant adequately justified the choice for the disease or health state being studied? Has the applicant provided a rationale for the cohort, the primary host phenotypes used for the selection of clinical biospecimens, and the choice of microbiome and body region(s) with respect to the proposed health or diseased states? Is there a clear rationale for why additional microbiome data beyond taxonomic composition are needed, as well as the choice of data and proposed methods?
• Is the proposed Center structure appropriate? Are the governance, management and succession plans well described and appropriate? Are communication strategies clear, including well described research network consortium meetings?
• Will the donor recruitment or biospecimen sampling plan presented provide the needed resource for this study? Are the number of samples appropriate, given the primary host phenotypes and data to be collected? Are the inclusion and exclusion criteria, sample acquisition plans, consenting or reconsenting and standard operating procedures for processing of the biospecimens for the proposed assays well described and appropriate? Does the applicant plan to carry out enrollment of a new cohort or consent a new cohort?
• Are the proposed sample analysis methodologies robust, cost-effective and state of the art? Has data quality been adequately addressed? Does the applicant have the infrastructure/laboratory information management needed for the proposed program?
• Are the informatics to be used to support data production, processing and incorporation into a combined dataset well described and appropriate? Have the approaches proposed to identify the data derivatives to go into the combined dataset well described and appropriate? Are there appropriate approaches to distinguish between host and microbiome contributions? Are there well described power analyses and statistical strategies?
• Has the applicant identified an appropriate potential "data snapshot" (i.e., data milestone time point) and described adequate proof-of-principle test plans? Are the plans to include external input adequate?
• Does the applicant have adequate plans for a proof-of-principle test of the final exploratory data set to be generated? Does he/she have adequate experience in utilizing the proposed analysis tools or in improving tools? Does the applicant have plans to engage the broader community in the proof-of-principle test of the useability of the dataset?
• Does the applicant have adequate plans for combining the data set and for release of the combined dataset to the broader community?
• Are the plans and policies adequate for release of all types of data generated through this project, including metadata? If human subject data, will the data be de-identified prior to deposition in a controlled access site(s)? If human subject data, are plans and procedures in place to release the data types into a controlled access site(s)? Are there plans and procedures in place for only qualified researchers to apply for and gain access to the data in the controlled access site? Is there evidence that the systems are in place to support rapid data release? Are there adequate plans for release or distribution of other resources, software, or technologies developed under this award? Has the application fully addressed the release of cohort subject and sequence data, metadata, any other data, analyses, clones and reagents?
• Does the applicant include detailed milestones and timelines? Are the proposed timelines and milestones appropriate for the various aspects of the project including sample generation, data generation, incorporation into a combined dataset, and release?

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?

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

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

Inclusion of Women, Minorities, and Children

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the 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 whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the National Institute of Dental and Craniofacial Research 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 response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center and 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 NIDCR 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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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

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

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

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

The Program Director/Principal Investigator (PD/PI) will have the primary responsibility for defining the details for the HMP Exploratory Microbiome Study within the guidelines of this FOA and for performing the scientific activities. The PD/PI will agree to accept close coordination, cooperation, and participation of NIH HMP Program staff in those aspects of scientific and technical management of the project as described under "NIH Program Staff Responsibilities."

The PD(s)/PI(s) of a HMP Collaborative Center will:

• Determine experimental approaches, design protocols, set project milestones and conduct experiments;
• Provide goals for production, quality, and cost of data to be generated to the NIH HMP staff as requested (usually at the outset of the award and annually thereafter, but also at other times as requested by NIH HMP staff);
• Ensure that the data produced meets the quality standards and costs agreed upon at the time of award or any improved quality standards and costs negotiated during the award period;
• Ensure that the data of all types (such as clinical data, reads, assemblies, metadata, expression data, mass spectra, proteomic data and metabolomic data, as both raw data and derived data) are deposited in the appropriate controlled access public database (e.g., SRA, GEO or other, as specified by NIH HMP staff) or, if needed, at appropriate controlled access websites (as agreed to at the time of the award), that resources developed as part of this project are made publicly available according to NHGRI and NIAID policies, and that results are published in a timely manner;
• Adhere to the NIH NHGRI and NIAID policies regarding intellectual property, data release and other policies that might be established during the course of this activity;
• Submit quarterly progress reports;
• Accept and implement any other common guidelines and procedures developed for the HMP program;
• Actively work to support and promote the Human Microbiome Project Research Network Consortium (HMP Consortium) goals and objectives;
• Organize/run the HMP Consortium meetings, to occur annually as face-to-face meetings and as virtual meetings and conference calls on a more frequent basis. The purpose of these meetings will include, but not be limited to, discussing 1) sample preparation and acquisition, 2) analytical procedures for the different data types, 3) data harmonization and standards for the different data types, 4) establishing the data milestones, 5) data structure for and creation of the combined test dataset, 6) computational challenges in testing the useability of the combined dataset, 7) identification or development of appropriate databases for archiving the primary and derived data produced under the FOA and 8) planning for publications. Best practices are expected to emerge from these discussions and will be shared through Center websites and in Consortium publications.

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:

NIH Project Scientists will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. NIH HMP Project Scientists will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination. However, the role of NIH HMP Project Scientists will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the HMP Consortium and NIH HMP Project staff will be given the opportunity to offer input to this process.

The Project Scientists will:

• Participate in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted. The Project Scientists will assist and facilitate the group process and not direct it;
• Negotiate throughput, quality, cost goals, and sampling needs with the awardees as necessary;
• Periodically report progress to the Directors of relevant NIH Institutes and Offices;
• Provide advice in the management and technical performance of the investigation;
• Assist in promoting the availability of the human microbiome data and related resources developed in the course of this project to the scientific community at large;
• Participate in data analyses, interpretations, and where warranted, co-authorship of the publication of results of studies conducted through the HMP Consortium;
• Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
• 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 award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award.

Additionally, an NIH 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. The assigned program director may also serve as the NIH Project Scientist.

Areas of Joint Responsibility include:

A Steering Committee will serve as the main governing board of the HMP Consortium. The Steering Committee membership will include NIH HMP Project Scientists and the PIs of each awarded cooperative agreement. The PI of each HMP Collaborative Center (or designee) will have one vote on the Steering Committee. The Project Scientists may vote, but the total NIH votes will count as a maximum of one-third of the total number of votes. The Steering Committee Chair will rotate on an annual basis and will not be an NIH staff member. Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. The Steering Committee will:

• Discuss progress in meeting the goals of the FOA.
• Agree which external community members should be formal members of the HMP Consortium. The HMP Consortium will consist of the funded grantees of awards made under this RFA as well as external members of the community, as appropriate. In some cases these members will not be funded through the HMP program but may bring specific expertise to the HMP Consortium. Membership considerations include contributions to the data processing or analysis of the combined test dataset or other contributions as needed in the HMP Consortium. New members will be announced at the next HMP Consortium meeting or via email to the HMP Consortium and each new member will be provided with a copy of the Consortium guidelines.
• Develop recommendations for uniform procedures and policies necessary to meet the goals of the HMP Consortium, for example for data quality measures and assessment, conventions for data deposition, or measuring costs and throughput.
• Serve as a venue for coordination on the improvement of human microbiome scientific methods, for example by disseminating best practices and collectively evaluating new procedures, resources, and technologies.
• Schedule the time for, and prepare concise (3 to 4 pages) summaries of the Steering Committee meetings, which will be delivered to members of the group within 30 days after each meeting.
• Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

External Scientific Consultants

The External Scientific Consultants (ESC) will be responsible for reviewing and evaluating the progress of the members of the Human Microbiome Project Research Network Consortium toward meeting their individual and collective goals. The ESC will provide recommendations to the Directors of NHGRI, NIAID, NIDCR, NIDDK and the NIH Office of Strategic Coordination about continued support of the components of the HMP program. The panel will be composed of three senior scientists with relevant expertise who are not P.I.s of a cooperative agreement involved in the HMP Consortium. The membership of the External Scientific Consultants may be enlarged permanently, or on an ad hoc basis, as needed.

The External Scientific Consultants will meet at least once a year with the HMP Consortium. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the ESC members to interact directly with the awardees. Annually, the ESC will make recommendations regarding progress of the HMP Consortium and present advice about changes, if any, which may be necessary in the HMP Consortium or the program to the Directors of NHGRI, NIAID, NIDCR, NIDDK and NIH Office of Strategic Coordination.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel will be convened. The Panel 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. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

Awardees will also be required to submit periodic (quarterly) progress reports in a standard format, as agreed upon by the Steering Committee and the ESC. As part of good program management, the NIH may request information essential to an assessment of the effectiveness of this Program. Accordingly, recipients are hereby notified that grantees may be asked to provide information for program evaluation purposes, both locally and at the national level.

The NIH will evaluate this program. Each awardee will be required to define concrete and quantifiable project-specific quarterly and 1 year milestones for the U54. Prior to funding the application, program staff will negotiate the milestones with the applicant. The negotiated milestones will become a condition of the award, including appropriate language to recognize that the project includes research the outcomes of which are unpredictable. Each awardee will be required to update these milestones annually at the anniversary date. In addition, each awardee is expected to provide additional information as required to assist the program evaluation. In accord with the procedures described above, NIH may withhold or reduce funds for a project that substantially fails to meet its milestones or to maintain the state of the art.

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.

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Lita M. Proctor, Ph.D.
HMP Coordinator
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane
Suite 4076
Bethesda, MD 20892
Telephone: 301-496-4550
Fax: 301-480-2770
Email: lita.proctor@nih.gov

Yasaman Shirazi, Ph.D.
Chief, Scientific Review Branch
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
National Institutes of Health
6701 Democracy Blvd., Room 662
Bethesda, MD 20892 (U.S. Postal Service Express or regular mail), Courier (20817)
Telephone: 301-594-5593
Fax: 301-480-8303
Email: yasaman.shirazi@nih.gov

Dede Rutberg, MBA
Lead Grants Management Specialist
Grants Management Branch
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
National Institutes of Health
6701 Democracy Blvd., Room 656
Bethesda, MD 20892 (U.S. Postal Service Express or regular mail), Courier (20817)
Telephone: 301-594-4798
Fax: 301-480-3562
Email: rutbergd@mail.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.