Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)

Components of Participating Organizations
This FOA is developed as a NIH Common Fund/Roadmap initiative. All NIH Institutes and Centers participate with the NIH Office of the Director in Common Fund/Roadmap initiatives.This FOA will be administered by NIAAA (http://www.niaaa.nih.gov) on behalf of the NIH (http://www.nih.gov).

Title:  Epigenomics of Human Health and Disease (R01)

Announcement Type
New

Update: The following update relating to this announcement has been issued:

Request for Applications (RFA) Number: RFA-RM-08-017

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV.

Catalog of Federal Domestic Assistance Number(s)
93.310

Key Dates
Release/Posted Date: July 16, 2008
Opening Date:  September 28, 2008  (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): September 28, 2008
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization). Application Due Date(s):  October 28, 2008
AIDS Application Due Date(s): Not applicable
Peer Review Date(s): February/March 2009
Council Review Date(s): May 2009
Earliest Anticipated Start Date(s): July 2009
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: October 29, 2008

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives


Section II. Award Information

1. Mechanism of Support

2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants

    A. Eligible Institutions
    B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information

2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Receipt, Review, and Anticipated Start Dates
          1. Letter of Intent
    B. Submitting an Application Electronically to the NIH
    C. Application Processing   
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices

2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contacts
1. Scientific/Research Contact(s)

2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

Nature of the Research Opportunity

The NIH invites qualified investigators from academic or research institutions to submit an application for this Funding Opportunity Announcement (FOA) whose goal is to address the Epigenomics of Human Health and Disease as part of the NIH Roadmap Epigenomics Program.

Epigenetic processes are critical to the normal development and function of multi-cellular organisms and play an important role in human disease. This FOA seeks to transform our understanding of the epigenetic contributions to human disease. The FOA focuses on research to define global (epigenome-wide) marks or features, and their possible interactions, in diseased, aged, or otherwise compromised human primary cells or tissues. These studies may also include follow-up epigenetic analyses to reveal function or significance of target gene regions or loci identified through the initial mapping activities. Characterizing the epigenomic components that may regulate the transcriptional potential of a cell and contribute to the etiology, severity or progression of human disease will provide novel insights into disease pathogenesis and therapeutic approaches. This knowledge will enhance our ability to investigate, diagnose and ameliorate human disease with a significant epigenetic component.

The NIH Roadmap is a series of programs designed to foster new ways of doing research, to fill fundamental knowledge gaps, and to encourage risk taking to solve complex problems. The overarching criterion for Roadmap programs is that they are expected to transform the way research is conducted across the spectrum of health research. The programs in their entirety therefore do not address specific diseases, although individual awards within a program may be disease-specific (http://nihroadmap.nih.gov/).

There are five related components of the Roadmap Epigenomics Program. Four of these have already been announced. The RFA numbers and titles are as follows: RFA-RM-07-013, Reference Epigenome Mapping Centers (REMCs); RFA-RM-07-014, Epigenomics Data Analysis and Coordination Center (EDACC); RFA-RM-07-011 (R01) and RFA-RM-07-012 (R21) Technology Development in Epigenetics; and RFA-RM-07-015 (R01) and RFA-RM-07-016 (R21) Discovery of Novel Epigenetic Marks in Mammalian Cells. The fifth component, this FOA, addresses the Epigenomics of Human Health and Disease.

It is anticipated that research funded by the Roadmap Epigenomics Program will ultimately have a significant impact on our ability to promote human health and prevent and treat human disease through the development of potential biomarkers, therapeutic targets and tissue regeneration strategies.

Purpose

The purpose of this funding announcement is to transform our understanding of the epigenomic basis of human disease. Applicants will discover and define global (epigenome-wide) marks or features, and their possible interactions, in diseased, aged, or otherwise compromised human primary cells or tissues. Studies using mammalian animal models will be allowed with appropriate justification addressing reasons why human tissues cannot be examined for the disease/condition of interest. The goal is to transform our understanding of human disease, aging, or response to insult by correlating changes in the epigenome with the altered cellular state. These discovery-based approaches to reveal epigenome-wide characteristics may also be followed up by epigenetic approaches that aim to reveal function or significance of target gene regions or loci identified during the initial mapping activities.

Background

The organization of DNA into chromatin presents the cell with the opportunity to use powerful regulatory mechanisms broadly defined as epigenetics. Increasing evidence demonstrates epigenetic mechanisms are linked to gene activation, gene silencing and chromosomal instability. Epigenetic processes act in cell specific, temporally regulated manners to direct normal development, differentiation, organogenesis, tissue formation, and aging. Epigenetics is an emerging frontier of science that involves the study of changes in the regulation of gene activity and expression that are not dependent on gene sequence. For purposes of this program, epigenetics refers to both heritable changes in gene activity and expression (in the progeny of cells or of individuals) and also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable. While epigenetics refers to the study of single genes or sets of genes, epigenomics refers to more global analyses of epigenetic changes across the entire genome.

Epigenetics is an emerging basic field of science as evidenced by the exponential increase in basic epigenetic research literature citations observed between 1990 and 2006. A similar pattern of escalating citations is now being documented with epigenetics and diseases, and multiple disease focused research grants have been awarded by the NIH in recent years. Understanding the temporal and tissue specific regulation of chromatin is fundamental to the study of epigenetics. The precise organization of DNA into chromatin uniquely directs gene expression via a series of powerful regulatory mechanisms broadly defined as epigenetic regulation. Increasing evidence demonstrates epigenetic mechanisms are linked to gene activation, gene silencing and chromosomal instability, but little is known about the molecular mechanisms themselves.

Epigenetic regulation of gene transcription apparently plays a pivotal role in the governance of normal and disease development through dynamic transcriptional activities from gametogenesis through embryonic and neonatal stages, and continuing throughout adolescence, adulthood and elderly stages/old age. Epigenetic research in human health is rapidly evolving and has reached a critical point where opportunities exist to make significant inroads in understanding how epigenetically regulated transcription directs functional processes in development and across the lifespan as well as in disease states.

Alterations in normal gene silencing and activation result in inappropriate patterns of gene expression, adversely affecting phenotypic plasticity and resulting in a broad spectrum of tissue dysfunction and disease outcomes, including but not limited to multiple cancers, autoimmune diseases, neurodegenerative disorders, liver diseases, respiratory disorders, developmental disorders, cardiovascular diseases, and behavioral disorders. The integration of epigenetics with genetics and environmental influences will be necessary to fully understand mechanisms of complex human diseases. Epigenetic mechanisms which are responsible for temporal and tissue specific activation or silencing of gene transcription include: DNA methylation of CpG islands in promoters and other regions of the genome; chromatin remodeling and higher order chromatin structural alterations; post-translational ATP-dependent modifications which include methylation, acetylation, ubiquitination, and phosphorylation of histone tail domains; and gene regulation through non-coding RNAs. There are likely additional epigenetic modifications and regulatory mechanisms that have not yet been discovered or elucidated.

Normal development and aging are also directed by epigenetic processes and can be affected by various environmental exposures resulting in alterations in the transcriptional potential of a cell or tissue type. This altered gene expression in many cases is stable and may persist leading to increased susceptibility to disease later in life and even across generations.

Epigenetic research has enormous potential for significantly furthering our understanding of human health and treatment of disease. Other long term potential benefits of the Roadmap Epigenomics Program include identification/elucidation of:

•   therapeutic targets and predicting responsiveness to therapy
•   mechanisms of disease
•   tissue repair/regeneration protocols
•   biomarkers of environmental exposures and disease
•   biomarkers of disease susceptibility

Objectives

Understanding the molecular basis of human biology and disease is of fundamental importance to the Institutes, Centers, and Offices of the NIH. Complex biological processes underlying states of health and diseases, which involve feedback between many genes and cells, are likely to be driven by epigenetic changes and responses as well as by allelic variations. Progression of disease may often be better explained by epigenetic alterations than by mutations. Several well established epigenetic marks (e.g. DNA methylation or specific histone modifications) are known to affect gene expression by affecting the transcriptional potential of cells. Other epigenetic alterations, such as trans-acting factors, post-translational modifications of particular proteins, and some non-coding RNAs are more recently discovered, and the mechanisms and significance of their roles in regulating cellular phenotype are only poorly understood. Additional, yet undiscovered epigenetic marks may exist as well, and identification of these novel marks could significantly advance our understanding of epigenetic regulation underlying human health and disease. The Discovery of Novel Epigenomic Marks RFA (RFA-RM-07-015/016) is intended to foster the discovery of novel marks.

The “epigenome” does not exist in the same sense as the “genome” of a species or an individual. Rather, many epigenomes or epigenomic profiles exist. Each one directs a specific gene expression profile and therefore the phenotype of a cell or tissue, and is highly dynamic as the cell responds to its environment and takes part in biological processes. For the purposes of this FOA, an “epigenome” is the epigenomic profile from a specific cell or tissue type which represents its biological condition or state (e.g., normal or homeostatic, perturbed in response to exogenous exposures, abnormal or diseased), defines its transcriptional potential, and provides clues about how epigenetic processes may regulate cellular function.

This announcement is intended to encourage the application of global epigenome-wide approaches to transform our knowledge of how the epigenome defines and contributes to human disease. It requires applicants to propose projects that employ unbiased, global approaches in human cells (or with rare exceptions, cells from mammalian models; see below) to correlate alterations in epigenomic structure/marks with disease, aging, or environmental perturbation. Following the initial global mapping, applicants may also propose to conduct epigenetic analyses to reveal the function or significance of target gene regions or loci identified during the initial global screen. Because the primary focus of an application should be the application of global mapping approaches across the genome, any proposed epigenetic analyses should be considered as follow up and secondary to the initial global mapping. Thus, applications that propose to focus the initial epigenome-wide mapping on a single gene, gene set, or restricted genomic region, or on epigenetic marks already known to be involved in a particular human disease will not be considered responsive to this FOA.

Thus, applicants should propose studies using epigenome-wide approaches in primary cells/tissues that represent compromised, abnormal or diseased states in humans, and include epigenome-wide analyses in comparative (control) normal or healthy cells/tissues for the disease under study. Examples of disease-related research areas that address physiologically compromised, abnormal or diseased states include:

•   perturbation due to exogenous exposure to dietary, chemical, social, or behavioral factors that may contribute to human disease

•   abnormal regulation of fundamental processes during critical stages of life (e.g., development, reproduction, aging) resulting in human disease

•   dysregulation of fundamental biological processes (e.g., inflammation, apoptosis, oxidative stress) that underlie multiple diseases.

Applicants may propose to map various epigenetic modifications such as but not limited to: regions or patterns of methylated DNA and/or CpG motifs, histone tail modifications (e.g., acetylation, phosphorylation, ubiquitination) or other components of chromatin structure and remodeling, and/or non-coding RNAs such as siRNAs (21-23 nucleotides), PIWI interacting or piRNAs (26-31 nucleotides), or germ line RNAs (24-29 nucleotides) that may be involved in epigenetic regulation.

Applicants should propose studies involving human cells and tissues (except under special circumstances, described below) and provide a rationale for the selection of cells/tissues for establishing the epigenomic maps. The rationale should describe how understanding changes in epigenomic marks or features, and their possible interactions, in perturbed or diseased states as compared to normal or healthy states will disrupt current paradigms concerning disease etiology or progression or how it will create new paradigms where none exists.

The NIH recognizes that insight into human diseases, such as brain-related disorders, may be restricted to animal models at present because appropriate human research models are not available. For diseases that cannot be pursued in human models, applicants may propose to work in mammalian models, but must provide a specific rationale for using an animal model to further the understanding of human disease because an appropriate human model is not available.

The NIH anticipates that cell/tissue systems for the study of some diseases may not be immediately amenable to global mapping approaches. Thus, applicants may propose projects whose initial aims involve the application of global approaches to characterize epigenomic profiles of normal physiology in healthy primary cells/tissues as a comparison for the disease of interest; however, the proposed aims must involve global epigenomic mapping in relevant (comparative) abnormal or diseased cells/tissues by year 3 of the project.

Comparative analyses involving more than one cell/tissue type, or disease state or process, may also be appropriate. Applicants may propose to investigate epigenomes in existing (archived) or new human biospecimens collected as part of other ongoing funded human clinical or epidemiological studies of human disease. Proposals seeking to initiate new human studies for the purpose of collecting biospecimens for epigenomic analysis are outside the scope of this funding announcement. However, the addition of an epigenome-wide mapping component, funded through this FOA, to an ongoing clinical or epidemiological study of human disease may be appropriate.

Research Scope

This FOA under the NIH Roadmap is intended to lead to fundamentally new paradigms of disease etiology and progression through identification of epigenomic contribution to disease processes. The scientific scope of this FOA is intentionally broad in order to address the collective research interests of the participating NIH Institutes, Offices and Centers. Because each NIH entity has a unique scientific purview and set of program goals and initiatives that evolve over time, it is strongly suggested  that all applicants, prior to preparing an application, consult the appropriate Institute representative, listed below in Section VII, to obtain current information about each Institute's program priorities.

Program Components

This FOA on the Epigenomics of Human Health and Disease is one component of the larger Roadmap Epigenomics Program. The purpose of this funding opportunity is to encourage the application of existing and newly emerging research knowledge and analysis tools to study of epigenomic contributions to human disease. Thus, applicants to this FOA are encouraged to utilize the resources being generated by other initiatives included in the Roadmap Epigenomics Program. For example, the research knowledge generated by the Reference Epigenome Mapping Centers (REMCs) (RFA-RM-07-013) may serve as relevant “reference” epigenome data for specific disease-related processes, states or conditions proposed under this FOA. In addition, investigators funded under this FOA may propose to engage in collaborative research activities with investigators funded under the REMCs to provide biospecimens for analytical services to be conducted by the REMCs.

An important aspect of the Roadmap Epigenomics Program is the development of an integrated database. The database will be created and maintained by the NIH National Center for Biotechnology Information (NCBI), in collaboration with the Epigenomics Data Analysis and Coordination Center (EDACC) (RFA-RM-07-014), and will serve as a resource for the Roadmap Epigenomics Program and other researchers working to unravel the components of disease and dysfunction in addition to providing important information about health and normal processes.

To ensure data obtained from the studies funded under this FOA can be utilized in the program database, applicants are expected to describe an informatics plan for processing the primary data to generate a list of the epigenetic marks or features found under the proposed experimental conditions. The plan should include a description of how primary data will be processed and transferred in standardized formats to the EDACC or directly to the NCBI as specified by the data release principles (see below). It will be essential for each application to demonstrate expertise in informatics to ensure data can be formatted and transferred to the NCBI in a format that is consistent with the other components of the Roadmap Epigenomics Program. Applicants may propose to utilize the EDACC to perform the data formatting and transfer to NCBI, and if so, are required to contact the EDACC PI and submit a letter of collaboration to ensure inclusion of their data in the EDACC activities and make financial arrangements to provide support for these activities.

Although individual grants funded under this FOA will be assigned to and managed by a lead NIH Institute or Center, all the funded projects will be linked programmatically to each other and to other funded projects in the Roadmap Epigenomics Program to facilitate information sharing and promote research collaborations.

Summary of Requirements

Applications responsive to this FOA should have the potential to dramatically transform our understanding of the epigenetic basis of one or more human diseases. In addition to describing how current paradigms concerning disease processes will be disrupted, responsive applications will:

 •  Clearly describe the relevance of the proposed work to a human disease. For some diseases, applications may initially focus on the epigenomic basis of an underlying biological process related to disease, but must address one or more relevant (comparative) human diseases by year 3 of the project.

•   Include a global epigenome-wide component, but may also include follow up epigenetic approaches.

•   Use human cells and/or tissues or provide a strong justification for why a mammalian model is scientifically appropriate. For example, an animal model could be justified when it would be extremely difficult or impossible to obtain the appropriate human cells or tissues, such as for some brain-related research.

•   Describe the informatics plan.

Evaluation

As part of good program management, NIH assesses the implementation and effectiveness of its programs using evaluation tools and techniques. Grantees may be asked to provide information for program evaluation purposes, both locally and at the national level. Such information may be used in evaluations of the initiative as well as the “Mid-Course” review of the entire Roadmap Epigenomics Program. Note that the Roadmap Epigenomics Program mid-course evaluation will be directed by the Roadmap Epigenomics Working Group. Applicants are advised to review the additional details on evaluation that are provided in Section IV.6. Application and Submission Information, “Other Submission Requirements.”

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information


1. Mechanism of Support

This FOA will use the R01 award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project. 

This FOA uses “Just-in-Time” information concepts (see SF424 (R&R) Application Guide). It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) must use the PHS398 Modular Budget component.

U.S. applicants requesting more than $250,000 in annual direct costs and all Foreign applicants must complete and submit budget requests using the Research & Related Budget component.

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.

 The total number of R01s awarded will depend on the number of applications received, their relative scientific merit, and the availability of NIH Roadmap and Individual Institute and Center funds.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004.

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.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

1.B. Eligible Individuals

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

More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH electronic Research Administration (eRA) Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering the multiple PD/PI option, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application.  Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information


To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, use the “Apply for Grant Electronically” button in this FOA or link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.

Several additional separate actions are required before an applicant can submit an electronic application, as follows:  

1) Organizational/Institutional Registration in Grants.gov/Get Registered

2) Organizational/Institutional Registration in the eRA Commons

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

Both the PDs/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo -- Telephone 301-435-0714; Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. Some fields within the SF424 (R&R) application components, although not marked as mandatory, are required by NIH (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6., “Special Instructions,” regarding appropriate required budget component.)  

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations (Non-Domestic [non-U.S.] Entities)

NIH policies concerning grants to Foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from Foreign organizations must:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States (U.S.) or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS  

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of “PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the “Credential” field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” [Section 14 of the Research Plan Component in the SF424 (R&R)], must be included. A rationale for choosing a multiple PD/PI approach should be described.  The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan.  In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award (NoA).

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions 

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form. 

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

Applications Involving Federal Agencies

The requests from federal agencies, including the NIH intramural program, will not include any salary and related fringe benefits for career, career conditional or other federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative costs).

In general, the budget requests will be limited to the incremental costs required for carrying out the proposed work. These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. While support for extramural collaborators may be requested in a separate grant application, funds can be requested for services by an external investigator or contractor as a subcontract/consortium including the applicable indirect (F&A costs) of the contractor/collaborating institution.

Justification must be provided for all requested support and for the Federal employees who will be committed to the project although no funds are requested in the application.

Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date: September 28, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): September 28, 2008
Application Due Date(s): October 28, 2008
Peer Review Date(s): February/March 2009
Council Review Date(s): May 2009
Earliest Anticipated Start Date(s): July 2009

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Brenda K. Weis, M.S.P.H., Ph.D.
Senior Science Advisor to the Director
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
5635 Fishers Lane
Room 2089, MSC 9304
Bethesda, MD 20892-9304
[Rockville, MD 20852-9304 (courier mail)]
Telephone: (301) 451-2067
Fax: (301) 443-7043
Email: weis@mail.nih.gov

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp  and follow Steps 1-4. Note:  Applications must only be submitted electronically.  PAPER APPLICATIONS WILL NOT BE ACCEPTED. 

In order to expedite the review, applicants are requested to notify the NIAAA Referral Office by email weis@mail.nih.gov when the application has been submitted.  Please include the FOA number and title, PD/PI name, and title of the application.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday – Friday, excluding Federal holidays) to view the application image to determine if any further action is necessary.

Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the Roadmap Epigenomics Working Group. Incomplete and non-responsive applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons. 

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on the application status in the Commons.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an “Introduction” describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. 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. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see the NIH Grants Policy Statement).

6. Other Submission Requirements and Information

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD(s)/PI(s) to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

Supplementary Instructions:

The following exceptions to the general R01 instructions will apply for this FOA:

Biosketches: Each biosketch is limited to four pages. The number of publications cited in the PI’s biosketch is limited to ten or fewer items. PIs should cite their most relevant publications and those that illustrate their ability to perform epigenomic analyses.  Publications that demonstrate exceptional innovation and significance need not be related conceptually to what the PI is proposing in this application. Following each cited publication, the applicant should very briefly summarize the findings or achievements described in the publication that demonstrate relevance to the proposed work, if not apparent in the title. Summaries should not exceed 60 words each. 

Research plan: The research plan is limited to 12 pages. It should be self-contained, since appendices and updates are not allowed. Omit the Specific Aims, Background and Significance, and Preliminary Studies sections. In the Research Design and Methods section, the applicant should address the following six points in a single PDF file with a separate subheading for each point. Applications will be evaluated by review panels that represent a diversity of scientific interests and expertise. Therefore, jargon must be avoided. Explain the challenge, the potential impact, and the approach in language that scientists with broad expertise can understand. 

1. The Challenge: What is the disease or condition that will be studied, and what is the hypothesis to be tested concerning epigenomic mechanisms underlying this disease/condition? How will the work disrupt the standard paradigm or create a paradigm where none exists?

2. The Potential Impact: How will the results transform our understanding of this disease/condition? How broad is the potential impact? Which community will be affected? What is the size of that community?

3. The Approach (limit, four pages): What are the epigenomic marks to be analyzed, and how will they be mapped across the genome and of which cells? Provide enough information that reviewers can determine what, in general, you are proposing to do, but do not include a detailed experimental plan. If your methodology is novel, what is unconventional and exceptionally innovative about your approach? How does your approach differ from what other investigators have attempted to do? If you plan to use mammalian cells, provide strong justification: why can human cells not be used to understand the disease of interest?

4. The Appropriateness of Roadmap: Why is the proposed research uniquely suited to the stated goals of the NIH Roadmap Epigenomics initiative? How does the proposed research differ from what is being done in your and other laboratories?

5. The Likelihood of Success: Briefly describe your prior efforts in the area of epigenomic mapping. What were the technologies used in your prior studies, how comprehensive have prior efforts been in determining the epigenomic structure of particular cells, and how do they compare to the current application? 

6. Timeline (limit, half a page): Provide a timeline for the proposed research. To facilitate evaluation of progress reports, describe when you anticipate that essential components of the project (e.g., acquisition of samples, optimization of protocols, critical experiments to verify the hypothesis, validation of novel tools or techniques) will be completed. 

Literature Cited: limited to one page. Note that the 12 page limit for the Research Plan does not include the Literature Cited section (separate Pdf.). 

Appendix: not allowed

No updates will be accepted.

Data Sharing:

To accelerate progress in the field of epigenomics, grantees will be expected to participate actively and openly in at least one grantee meeting per year. Substantial information sharing is critical to the program, so how an applicant plans to achieve this would be considered as a term and condition of the award; failure to openly share information will be considered in continued funding consistent with achieving the goals of the program. It is understood that some information developed under the grants will be proprietary and cannot be shared immediately without damaging the commercialization potential of the scientific discovery or in some cases jeopardizing the protection of human subjects. Applicants should describe their plans for participating in the grantee meetings and for managing any appropriate intellectual property concerns in the context of those meetings and other opportunities for information sharing in the Other Research Plan Sections under Resource Sharing Plan(s) attachments section.  Other investigators in the field (i.e., not supported under this program) may be invited to participate in these meetings, but their agreement to share information substantially will be a prerequisite to their participation. Applicants should budget for travel funds for the PD/PI and one additional lead investigator to attend the annual meeting.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value and further the advancement of the research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.)

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources or state appropriate reasons why such sharing is restricted or not possible (see Sharing Model Organisms Policy, and NOT-OD-04-042.)

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (e.g., blood pressure or weight) or the presence or absence of a disease or condition.  For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

The adequacy of the resources sharing plan and any related data sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3. Award Administration Information, “Reporting.”

As the Roadmap Epigenomics Program is a community resource program, NIH expects that not only data, but also resources generated during the course of the program should be made rapidly available to the research community and that sharing plans should follow the same principles and spirit as the proposed rapid data release policy. The applicant should provide specific plans for resource sharing and distribution in the application. The reasonableness of the data sharing plan will be assessed by the reviewers. If resource sharing and/or data sharing are not possible, perhaps due to restrictions inherent to the informed consent process or concerns that human subjects’ privacy could be compromised, the application should describe why sharing is not possible.  However, reviewers will not factor the proposed resources sharing plan into the determination of scientific merit or the priority score. The adequacy of the resources sharing plans will be considered by the funding organization when making recommendations about funding applications. The presence of a resources sharing plan will be part of the terms and conditions of the award. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Award Administration Information, “Reporting.”

Technology and Data Sharing Overview

This initiative is part of a broader program in Epigenomics funded as part of the NIH Roadmap. In order to fulfill requirements for oversight of the Roadmap Epigenomics Program as a whole, NIH staff may need to present status reports on individual initiatives to coincide with NIH Office of the Director timeframes. Thus, in addition to the annual Non-Competing Grant Process Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm), awardees may be required to submit additional progress updates at a time to be determined by NIH. Program staff will use information from reports, site visits, etc. to evaluate each grantee’s progress and the success of the overall program. Progress will also be evaluated with the assistance of external advisors at the annual meeting and at the mid-course review of the entire Roadmap Epigenomics Program (see “Management and Evaluation” below).

Management and Evaluation

The project management team will evaluate the grants through annual progress reports and through annual All Hands Roadmap Epigenomics Program meetings starting in year 1 of the award. PIs of funded projects will be required to attend at least one grantee meeting per year for project evaluation and to facilitate technology transfer to the other components of the Roadmap Epigenomics Program. The annual meeting will include program staff, external advisors, and PIs from all funded awards in the Roadmap Epigenomics Program.

Sharing with other Roadmap Epigenomics Program Grantees

To accelerate progress in the field of epigenomics, grantees will be expected to participate actively and openly in at least one grantee meeting per year. Substantial information sharing is critical to the program, so how an applicant plans to achieve this would be considered as a term and condition of the award; failure to openly share information will be considered in continued funding consistent with achieving the goals of the program. It is understood that some information developed under the grants will be proprietary and might not be shared immediately without damaging the potential patenting or commercialization opportunities, or compromising the protection of human subjects. Applicants should describe their plans for participating in the grantee meetings and for managing any appropriate intellectual property concerns in the context of those meetings and other opportunities for information sharing in the Other Research Plan Sections under Resource Sharing Plan(s) attachments section If resource sharing or data sharing is not possible, perhaps due to restrictions inherent to the informed consent process or concerns that human subjects’ privacy could be compromised, the application should describe why sharing is not possible.  Other investigators in the field (i.e., not supported under this program) may be invited to participate in these meetings, but their agreement to share information substantially will be a prerequisite to their participation. Applicants should request travel funds in their budgets for the principal investigator and up to one additional lead investigator to attend the annual meeting.

Intellectual Property Management Plan

Certain research plans will require collaboration and coordination among investigators at different institutions, some of whom may not be NIH funding recipients and may have pre-existing intellectual property obligations to third parties. It is anticipated that commercial embodiments of the results of such research may incorporate single inventions shared by several institutions, or multiple inventions each from a separate institution. Therefore, prior to funding, grant applicants are expected to address, for example, how they will coordinate patent prosecution and licensing activities, if necessary to enable a licensee to access the bundle of intellectual property needed to take a product to market on commercially viable terms. Suggested strategies include: (1) assigning intellectual property rights to related inventions to an invention management firm; (2) designating one organization to take the lead on patenting and licensing related inventions; and (3) agreeing in advance that if multiple parties are to independently license-related inventions, the total of stacked royalties will not exceed a predetermined percentage rate. The technology transfer/ intellectual property management/licensing officer or equivalent of the PI's institution is expected to submit an intellectual property management plan, including at least those elements above. Alternatives to the suggested strategies, which accomplish the same goals, will be considered. Intellectual property management plans are a just-in-time requirement and do not need to be included in the grant application but plans will be required before a grant can be awarded. The applicant's institution should avoid exclusively licensing those inventions that are research tools unless either: (1) the field of use of the exclusive license is restricted to commercial use; or (2) the exclusive licensee will make the research tool available on reasonable terms. Applicants are directed to the NIH policy on the dissemination of biological research resources (“research tools”) at http://grants.nih.gov/grants/intell-property_64FR72090.pdf.

After completion of the initial review, NIH program staff will be responsible for any additional administrative review of the plan for sharing data. The adequacy of the data sharing plan, or explanation for why data sharing is not possible, will be considered by program staff of the funding organization when making recommendations about funding applications. The final accepted data sharing plan will become a term and condition of the award. The effectiveness of the data sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm).

Foreign Applications (Non-Domestic [non-U.S.] Entities)

Indicate how the proposed project has specific relevance to the mission and objectives of the NIH/IC and has the potential for significantly advancing the health sciences in the United States. 

Section V. Application Review Information


1. Criteria 

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to this FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Center for Scientific Review (CSR)  in accordance with the review criteria stated below.

As part of the scientific peer review, all applications will:

Applications submitted in response to this FOA will compete for available funds with all other recommended applications submitted in response to this FOA. The following will be considered in making funding decisions:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals.

Significance and innovation will be the primary determinants of the score. The approach will be evaluated for general feasibility. An application will score poorly if it is clear that the proposed methodology has no probability at all of being successful, either because it is inherently illogical or because the same approach has already been attempted and shown not to be feasible. Neither unavoidable risk, which is intrinsic to novel and innovative approaches, nor lack of preliminary data will preclude an application receiving an outstanding priority score.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? How important is the problem or hypothesis? If the effort is successful, how significant will the impact be and how broad is the community that will be affected? How will scientific knowledge or clinical practice be transformed? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the application address the goals and objectives outlined in the RFA; that is, does the proposed work have the potential to transform our understanding of the epigenomic components of human disease?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area? Does the project provide an innovative way to think of disease? If the project is successful, will it represent a transformative step in our understanding of disease? Will existing paradigms be altered and/or will new paradigms be created?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? For applications designating multiple PDs/PIs, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs? Does the applicant provide a rationale for the selection of cells/tissues that is compelling for the disease/condition of interest? Does the applicant propose to work in human cells/tissues or provide a specific rationale for using a mammalian animal model because an appropriate human model is not available?  Is the experimental plan logical such that there is at least some likelihood that the project will succeed? Does the applicant identify adequate informatics expertise and include evidence and assurances that a working relationship with the REMCs will be in place so that all data obtained through the study will be formatted in a manner that is consistent with the Roadmap Epigenomics Mapping Centers (REMCs)?

Investigators: Are the PD(s)/PI(s) and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Do(es) the PD(s)/PI(s) and investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment:  Do(es) the scientific environment(s) in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ critical collaborative arrangements (such as the arrangements with the EDACC and/or REMCs)? Is there evidence of institutional support?

2.A. Additional Review Criteria

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the rating:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed.  See the “Human Subjects Sections” of the PHS398 Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. See the “Human Subjects Sections” of the PHS398 Research Plan component of the SF424 (R&R)
 
Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the adequacy of the plans for their care and use will be assessed. See the “Other Research Plan Sections” of the PHS398 Research Plan component of the SF424 (R&R). 

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. The priority score should not be affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed. 

2.C. Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score. Program staff within the IC will be responsible for monitoring the resource sharing.

The appropriateness of a data sharing plan will be part of the terms and conditions of the award.

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information


1. Award Notices

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 NIH eRA Commons

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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. See Section IV.5. “Funding Restrictions.”       

2. Administrative and National Policy Requirements

An NIH Program Official from one or more of the participating NIH ICs will be assigned to each funded application and will assume responsibility for normal stewardship of the awards. The various Program Officials with responsibility for managing individual applications funded under this initiative will work in concert with one another and with members of the Roadmap Epigenomics Working Group to assist with convening regular grantees meetings of the funded PIs, and promote data sharing and collaboration across funded investigators of all components of the Roadmap Epigenomics Program.

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.

3. Reporting

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

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

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research (program), peer review, and financial or grants management issues:

1. Scientific/Research Contact(s):

For general information regarding this FOA, contact:

J. Patrick Mastin, Ph.D.
Acting Deputy Director
Division of Extramural Research and Training
NIEHS
111 T.W. Alexander Drive
PO 12233, Mail Drop K3-05
Research Triangle Park, NC 27709
Telephone:  919-541-3289
Email:  mastin@niehs.nih.gov

For Institute and Center mission-specific questions, contact appropriate Epigenomics Working Group Members (http://nihroadmap.nih.gov/epigenomics/members.asp).

2. Peer Review Contact(s):

Richard Panniers, Ph.D.
Center for Scientific Review
Division of Molecular and Cellular Systems
6701 Rockledge Drive
Room 2198, MSC 7840
Bethesda, Maryland 20892-7840
Telephone: (301) 435-1741
FAX: (301) 480-1988
Email: pannier@csr.nih.gov

3. Financial/Grants Management Contact(s):

Carolyn K. Mason
Deputy Grants Management Officer
Grants Management Branch
Division of Extramural Research and Training
NIEHS
111 T.W. Alexander Drive
PO 12233, Mail Drop K3-11
Research Triangle Park, NC 27709
Telephone:  919-541-1373
Email:  mason6@niehs.nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing). Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are: (1) first produced in a project that is supported in whole or in part with Federal funds; and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for Federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the National Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. 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. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.


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NIH Funding Opportunities and Notices


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