Department of Health and Human Services


Part 1. Overview Information
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/). This FOA will be administered by the National Institute of Mental Health (NIMH), (http://www.nimh.nih.gov/index.shtml) on behalf of the NIH.

Funding Opportunity Title

Adaptation of Scalable Technologies to Illuminate the Druggable Genome (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices
  • November 18, 2014 - See Notice NOT-RM-14-018. Request for Information (RFI): Input on Direction of the Second Phase of the "Illuminating the Druggable Genome" Program.
Funding Opportunity Announcement (FOA) Number

RFA-RM-13-010

Companion Funding Opportunity

RFA-RM-13-011, U54 Specialized Center--Cooperative Agreements

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

 93.310 

Funding Opportunity Purpose

The overarching goals of this Funding Opportunity Announcement (FOA) and the companion announcement (RFA-RM-13-011) are to foster the development of technologies and information management to facilitate the unveiling of the functions of the poorly characterized and/or un-annotated members in four protein classes of the Druggable Genome. This FOA calls for adaptation of an ensemble of scalable technology platforms to characterize functions of proteins as a large group at molecular and cellular levels in medium- to high-throughput fashion, rather than repeating the “one at a time” approach that might otherwise be undertaken. The objective is to establish transformative scalable technology platforms and streamlined experimental workflows incorporated with multiple robust assay and physiological perturbation protocols for large-scale functional studies of poorly characterized and/or un-annotated proteins encoded by the Druggable Genome. Applications are invited to adapt well-established scalable technologies as well as innovative scalable approaches to enable swift, cost-effective, and robust interrogation of molecular and cellular functions of proteins. Applications should address limitations and gaps of prior technologies/technology platforms as a benchmark against which the improvements or competitive advantages of the proposed ones are measured. These transformative technology platforms should provide sensitivity, selectivity, scalability, spatiotemporal resolution and reproducibility in analyses of protein functions in complex biological tissues, living organisms, or another physiologically relevant system.  

Key Dates
Posted Date

September 16, 2013

Open Date (Earliest Submission Date)

November 11, 2013

Letter of Intent Due Date(s)

November 11, 2013

Application Due Date(s)

December 11, 2013, by 5:00 PM local time of applicant organization.

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

AIDS Application Due Date(s)

December 11, 2013, by 5:00 PM local time of applicant organization.

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

Scientific Merit Review

March 2014

Advisory Council Review

May 2014

Earliest Start Date

July 2014

Expiration Date

December 12, 2013  

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

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

Part 2. Full Text of Announcement


Section I. Funding Opportunity Description


Background

This initiative is funded through the NIH Common Fund, 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.

Recent advances in genome-wide biology and focused biological studies have revealed a great deal about the human proteome, although significant portions remain poorly characterized and/or un-annotated. This paucity of annotation in portions of the genome and proteome has resulted in reduced priority given to exploring the so-called ‘dark matter’ of the genome. Although the Druggable Genome has been described as “…the subset of the ~30,000 genes in the human genome that express proteins able to bind drug-like molecules”, the existing clinical pharmacopeia is represented by only a few hundred targets. Within this understudied subset it is estimated that upwards of 6000 proteins may be druggable. Many proteins remain unstudied until an initial, highly-relevant biologic observation is made or a critical tool is developed, which then draws a tremendous amount of effort to the protein (the Harlow-Knapp effect). Thus, many interesting and critical biological processes and potential therapeutic avenues remain unexplored because an initial, catalyzing event has not yet been discovered. The “Illuminating the Druggable Genome (IDG)” will address this bottleneck by systemically querying this ‘dark matter’ to facilitate discovery that will shed light on this ‘dark matter.’

A large number of genes in the Druggable Genome belong to four well-studied and druggable protein families – the G-protein coupled receptors (GPCRs), ion channels, nuclear receptors (NRs), and protein kinases. Each of these families has many more members than those that are known targets, suggesting that with increased knowledge the Druggable Genome can be expanded. One limitation in discovery of new targets is a lack of knowledge of the underlying biology of these poorly characterized and/or un-annotated members of the Druggable Genome. Two important requirements for deep annotation of these genes and their encoded proteins are additional information and appropriate technology to foster discovery. The purpose of this program is to focus initially on proteins that comprise the ‘dark matter’ of the Druggable Genome that are members of the GPCR, NR, ion channel and kinase families. The elucidation of novel functions of these proteins is itself a daunting task and the focus on availability of validated reagents and known technologies within these classes will serve as a sound starting point for these efforts. Attempts to define a list of proteins in this unexplored space gave hundreds of potential individual opportunities, reinforcing the need to prioritize. It is expected that applicants to this FOA will address issues around the throughput of proposed technologies and, when appropriate, how to initially prioritize proteins within this unexplored space.

Thus, the overall long-term goals of the IDG concept are three-fold:

This FOA focuses on the first long-term goal through the adaptation and development of scalable technologies required to further the illumination of the Druggable Genome. It is expected that technology platforms supported by this program will be able to explore the underlying biology of large numbers of proteins within the listed four families of the Druggable Genome in ways that will provide prioritization to identify promising areas for future expanded study. Awardees are expected to work together to share expertise, tools, and resources throughout the grant period. A companion announcement (RFA-RM-13-011) will serve to create a Knowledge Management Center (KMC) to centralize and increase the accessibility of, and highlight the gaps in, existing information around these proteins. Through close associations, the components of the IDG will assess existing data and determine the feasibility of new technological approaches to prioritize subclasses of the poorly characterized and/or un-annotated members of the Druggable Genome.

Objectives and Scope

Biological functions of a protein may be inferred and characterized based on its intrinsic properties and extrinsic connectivity. A wide array of approaches are used to deduce protein functions, including experimental studies of anatomical and subcellular localization as well as bioinformatics analyses utilizing gene sequence homology, protein domain structures, and functional connectivity pathways. Furthermore, the functions of a protein may be characterized by experimentally assessing the effects and phenotypes induced by dosage manipulation of gene expression, binding of small- or macro-molecule ligands, or perturbations to its cellular localization and connectivity. While modern molecular genetics techniques have advanced to the point that genome-wide characterization of gene transcription and systematic approaches to studying knockout animals can be pursued, technologies to directly interrogate the function of proteins have not yet been widely adapted to the scale required for unbiased study of a large number of proteins. Given the number of medium- and high-throughput technology platforms available to study individual members of the GPCRs, NRs, ion channels, and kinases, it is possible that adaptation of many of these scalable technologies in a coordinated fashion will generate necessary knowledge and tools to foster a systematic illumination of function of a relatively large number of proteins.

This FOA seeks to assemble a group of scalable, transformative, and robust technology platforms that are relatively well-established and can be fully adapted to provide biological insights within a 3-year project period rather than to support development of those technologies that are still in conceptual stages.  Examples of such scalable technology platforms include but are not limited to the following:

A. Scalable technologies for individual protein families

GPCR

G-protein-coupled receptors (GPCRs) transduce a broad array of extracellular signals and ligands that include protein hormones, neurotransmitters, peptides, amino acids, nucleotides, fatty acid derivatives, Ca2+, odorants, and photons. Ligand binding to GPCRs results in a conformational change that leads to activation of intracellular heterotrimeric G proteins and receptor phosphorylation followed by a cascade of intracellular signaling events to regulate cellular functions. This FOA calls for the adaptation of established and emerging scalable technologies for the illumination of more than 100 non-olfactory GPCRs. Applications are invited to address questions including, but not limited to, the following:

Nuclear receptor

The Nuclear Receptor Signaling Atlas (NURSA; www.nursa.org) together with numerous ‘omic projects have provided abundant information regarding gene expression, cis-acting elements, trans-acting factors, epigenetic status, and chromatin structure of the NR superfamily. Over the past decade, the field has generated a large volume of data on the regulation of gene transcription by the 48 human NRs and their >300 co-regulators. Nonetheless, there is a subset of the NRs for which no known ligand has been identified and for which physiological function is still unclear. Such function may only be fully appreciated in a dynamic context of the whole cell or whole animal following spatiotemporal manipulation of NR activities. This FOA calls for the adaptation of scalable technologies for the illumination of poorly characterized and/or un-annotated NRs and their co-regulators under physiological and pathophysiological perturbations, using model animals and/or human-derived tissues and cells. Applications are invited to address questions including, but not limited to:

Ion channels

Recent technological advancements in genomics, proteomics and automated electrophysiology have presented opportunities to rapidly explore functions of ion channels that have been traditionally recalcitrant to high throughput approaches. There is a growing list of ‘channelopathies’ that link dysfunctions of ion channels to brain disorders, cardiac arrhythmia, diabetes, kidney failure, blindness, cystic fibrosis,  and a variety of rare disorders. Furthermore, opportunity exists to discover novel ion channel families and channel auxiliary proteins within the group of 2,000 – 4,000 transmembrane proteins of unknown function through unbiased screening approaches. This FOA calls for the adaptation of scalable technologies to characterize functions of poorly characterized and/or un-annotated ion channels. Applications are invited to address questions including, but not limited to, the following:

Kinase

By catalyzing phosphorylation of proteins and other biomolecules, kinases act as molecular switches and modulators to control many important molecular and cellular functions including enzyme activities, protein-protein interactions, receptor subcellular translocations, and ion channel activities.  In the past decade, a variety of scalable technologies (e.g., mass spectrometry coupled with chromatography, chemical proteomics, etc.) and tools (siRNA, chemical inhibitors, etc.) have been developed for the analysis of molecular and cellular functions of kinases, raising opportunities to characterize kinase functions in a high throughput manner. Despite considerable progress, significant numbers of protein kinases remain poorly characterized and/or un-annotated with respect to physiology and disease. This FOA calls for scalable technology platforms to address questions including, but not limited to, the following questions of the poorly characterized and/or un-annotated kinases in native tissues:

B. Scalable technologies across the four protein families

Protein-protein interactions

Protein-protein interactions are of great interest as they mediate a wide range of cellular responses to external stimuli and internal signaling. As an example, recent proteomic studies on ion channel complexes have revealed novel protein components and thus provide new insight into ion channel function and regulation. IDG is particularly interested in the study of protein connectivity and protein dynamic interplay for the poorly characterized and/or un-annotated proteins under physiological and pathophysiological perturbations. This FOA calls for scalable technology platforms to study protein interactions in native tissues or another physiologically or pathophysiologically relevant system that preserve the protein association with other binding molecules and stoichiometry. Examples include but are not limited to:

Post translational modifications (PTMs)

PTMs regulate protein activity, localization, and interaction with other biomolecules, including phosphorylation, glycosylation, ubiquitination, nitrosylation, acetylation, methylation and lipidation. To illuminate the role of PTMs and their manifestations for the poorly-characterized and/or un-annotated proteins within the Druggable Genome, this FOA  calls for adaptation of MS methods (e.g., multiple reaction monitoring (MRM-MS) and their robust applications to detect particular combination of PTMs in native tissue following a defined physiological or pathophysiologically-relevant perturbation.  Specific issues related to the adaptation of scalable MS technologies for PTMs include but are not limited to:

Section II. Award Information
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 scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The Common Fund intends to commit $2,500,000 in FY 2014 to fund 5-7 awards.

Award Budget

Application budgets will be capped at $275,000 Direct Costs, but should reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is 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.

Section III. Eligibility Information


1. Eligible Applicants


Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions

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

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

Required Registrations

Applicant Organizations

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility


Number of Applications

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

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:

Section IV. Application and Submission Information


1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

Letter of Intent

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

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

The letter of intent should be sent to:

Yong Yao, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Blvd, Rm 7182B, MSC 9641
Bethesda, MD 20892-9641
Phone: 301-443-6102
Email: yyao@mail.nih.gov

Page Limitations

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

Required and Optional Components

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed. Detailed budgets are required.  PD(s)/PI(s) should dedicate a minimum of 2 person months to this project. Travel for project personnel to attend the annual IDG Consortium meetings should be included in the budget.

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy: The objectives of the applications submitted should be relevant to and compatible with the goals specified in this FOA. Applicants may propose the adaptation of a technology platform with well-integrated components to query important protein functions within single families, across families, or a mixture of both. Applicants may propose a strategy to study a subset of well-characterized proteins and a subset of proteins of unclear functions from sample lists of poorly characterized and/or un-annotated proteins (e.g., http://www.iuphar-db.org/; http://baderlab.org/Data/RoadsNotTaken). It may be necessary to define those that can serve as a positive control to refine and set up robust technology platforms in order to evaluate and validate through pilot study the technology platform(s).   Applicants are expected to clearly discuss limitations and gaps of prior technologies/technology platforms as a benchmark against which the improvements or competitive advantages of the proposed ones are measured. The transformative technology platforms should strive to provide sensitivity, selectivity, scalability, spatiotemporal resolution and reproducibility in analyses of protein functions in complex biological tissues, living organisms, or a physiologically relevant system with the need for medium-to-high-throughput capabilities. Also applicants are expected to clearly discuss previous achievements in the research of relevant protein functions as well as potential outcomes from adapting the proposed technology platforms for the large-scale studies of poorly characterized and/or un-annotated proteins. Applicants are expected to establish alliances/collaborative partnerships where they are appropriate or needed to facilitate achievement of and add value to the research goals. The project should take advantage of the best available tools and resources available to the scientific community. Letters of collaboration and institutional support should show strong commitment to the project.

Milestones

A description of annual milestones to be achieved is required.  The annual milestones proposed in the application should be quantifiable and scientifically justified to allow the NIH program staff to assess progress. It is expected that the scalable technology platforms supported under this program will have been established fully and ready for use to study the poorly-characterized proteins in the Druggable Genome within the 3-year project period. The application should propose the annual milestones based on the technology readiness level as determined by the maturity of currently existing technologies (devices, materials, components, software, reagents, experimental conditions, work flows, etc.).  Overall the awardees are expected to:

The milestones will be evaluated by the scientific review panel. Applications lacking this information, as determined by the NIH staff, will not be reviewed. The clarity and completeness of the U01 application with regard to specific goals and feasibility milestones are critical. The proposed milestones should not be more than one page and are to be included within the page limit of the Research Strategy. Prior to funding an application, the program staff will contact the applicant to discuss the proposed milestones and any changes suggested by the review panel as indicated in the Summary Statement. The program staff and the applicant will negotiate and agree on a final set of milestones as the basis for judging the success of the U01 work. 

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 SF424 (R&R) Application Guide, with the following modification:

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

Foreign Institutions

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

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

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

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

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

4. Intergovernmental Review (E.O. 12372)

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 only as described in the NIH Grants Policy Statement.

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness 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.

Applications Involving the NIH Intramural Research Program

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests 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 or F&A costs). 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. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits. 

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights. 

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information


1. Criteria

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.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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? Will the technology platform generate high quality data, key knowledge and/or transformative tools to foster the study of poorly characterized and/or un-annotated members of the Druggable Genome? Will the technology platform significantly enable understanding fundamental mechanisms, physiology and disease processes, and/or identifying novel therapeutic targets?

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? Are PD(s)/PI(s) committed to the collaborative approach embodied in the cooperative agreement mechanism?

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? Will novel functions of poorly characterized and/or un-annotated members of the Druggable Genome be elucidated in a highly effective way via the proposed technology platform?

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? Does the technology platform provide sensitivity, selectivity, scalability, spatiotemporal resolution and reproducibility in analyses of protein functions in complex biological tissues, living organisms, or another physiologically relevant system? Does the scalable technology platform have significant advantages in performance and throughput over other existing platforms? Does the technology platform integrate adequate individual components including, if relevant, device, software, biospecimens of interest, reagents and sample preparation, robust assay and perturbation protocols? Is there a sound strategy to set up and validate the proposed technology platform?  Will the technology platform be established within the 3-year project period with characteristics of being reproducible and transferable for large-scale implementation based on the current technology readiness level?

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

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?  Has the applicant established alliances/collaborative partnerships where they are appropriate or needed to facilitate achievement and added value of the research goals? Does the project take advantage of the best available tools and resources available to the scientific community to-date? Do the letters of collaboration and institutional support show strong commitment to the project?  

Additional Review Criteria

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

Milestones

Are appropriate, evaluative and quantitative milestones provided and clearly defined? Are the milestones feasible and quantifiable for the proposed specific aims? How well do the proposed milestones align with the anticipated critical activities of the project?  Are the timelines appropriate? Do the milestones establish feasibility for all aspects of the proposed research?

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 Guidelines for the Review of Human Subjects.

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 Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

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

Additional Review Considerations

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

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, 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:

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information


1. Award Notices

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

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

2. Administrative and National Policy Requirements

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

Cooperative Agreement Terms and Conditions of Award

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

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

The IDG Program: 

This is the Illuminating the Druggable Genome program developed through the NIH Common Fund to address the special opportunities related to uncovering new information about the Druggable Genome.  The opportunities are defined by the companion Knowledge Management Center (KMC) and Technology Development initiatives (RFA-RM-13-011 and -010, respectively) for cooperative agreement awards. The IDG program is described in the portal: https://commonfund.nih.gov/IDG/.

The IDG Consortium: 

This includes the PIs of the set of funded KMC and Technology Development awards and the NIH IDG Working Group.

IDG Steering Committee: 

This is the primary forum of the IDG Consortium. The PI(s)/PD(s) of the awards from both KMC and Technology Development projects and the NIH Lead Science Officer serve on the Steering Committee.  See further details about the Steering Committee under Terms and Conditions Section VI.2, Areas of Joint Responsibility.

NIH IDG Working Group: 

The IDG Working Group of trans-NIH staff will provide coordination for, and management and oversight of, the IDG Program. Membership will include representatives from NIH Institute and Center program staff. The Working Group will receive recommendations from the Steering Committee and the External Scientific Panel. Working Group approval will be required for adoption of Steering Committee recommendations and for the initiation of collaborative projects within the Consortium. The Working Group will report to the NIH Institute and Center Directors (ICD) co-chairs from the sponsoring NIH Institutes.

The IDG Consortium will rely on collegial and cooperative interactions among its members. 

External Scientific Panel (ESP):

This will be composed of senior scientists with relevant expertise who are not PI(s)/PD(s) or supported by an award in the IDG Initiative.  NIH will appoint the members. The ESP will be responsible for evaluating the progress of the IDG Initiative, including the IDG KMC and Technology Development projects. See more about the ESP below.

Each year there will be an IDG Consortium Meeting in the DC Metro area. The Consortium Meeting will be held back-to-back with a meeting of the External Scientific Panel. Each project will present its research findings at this meeting. 

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

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

In addition, the NIH Program Officer will:

Other NIH Program Staff:

Areas of Joint Responsibility include:

The Steering Committee is responsible for coordinating the activities of the IDG Projects and is the committee through which the NIH IDG Working Group formally interacts with the IDG Consortium.  Steering Committee membership will include the PI of each Project, (limited to one person for a Project with multiple PIs) and the NIH Lead Project Scientist, each of whom will have one vote in IDG Steering Committee actions. The IDG Steering Committee Chair will be appointed by the NIH and drawn from the individual project PIs. The IDG Steering Committee may add additional, non-voting, members, as needed. Other government staff may attend the IDG Steering Committee meetings, if their expertise is required for specific discussions. The IDG Steering Committee may set up subcommittees as needed.

There will be periodic teleconferences at an agreed upon schedule to coordinate activities of the IDG Steering Committee.

There will be one annual in-person Consortium meeting which will involve the ESP. PIs for each project will include travel to attend such meetings in their budgets. The Administrative Core of the KMC will be responsible for convening IDG Steering Committee meetings.

Together, the members of the IDG Steering Committee will: 

External Scientific Panel (ESP):

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16..

3. Reporting

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

Scientific/Research Contact(s)

Yong Yao, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-6102
Email: yyao@mail.nih.gov

Peer Review Contact(s)

Raymond Jacobson, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-996-7702 
Email: jacobsonrh@csr.nih.gov

Financial/Grants Management Contact(s)

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: tjarosik@mail.nih.gov 

Section VIII. Other Information

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

Authority and Regulations

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


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