EXPIRED
National Institutes of Health (NIH)
National Institute of Mental Health (NIMH)
PsychENCODE: Non-coding Functional Elements in the Human Brain and their Role in the Development of Psychiatric Disorders (Collaborative U01)
U01 Collaborative Research Project Cooperative Agreements
Reissue of RFA-MH-14-020
PAR-17-258
PAR-17-257 -U01 Research Project Cooperative Agreements
93.242
The objective of this FOA is to support research in the discovery and characterization of the full spectrum of human-specific non-coding functional genomic elements across brain regions, cell types, and developmental time periods to elucidate their role(s) in the molecular pathophysiology of mental illness. It is expected that projects under this FOA will apply unbiased genome-wide approaches, computational methods, and experimental assays to identify and characterize functional genomic elements in both healthy and diseased human brains to correlate findings with development of mental illnesses and outcomes relevant to brain function and dysfunction. Projects should work towards developing comprehensive maps of functional elements, including insulators, enhancers, promoters, silencers, transcription binding factors, non-coding RNAs (e.g., long non-coding RNAs [lncRNAs], microRNAs [miRNAs], piwi-interacting RNAs [piRNAs]), modifications to RNA, RNA spliceoforms, long-range chromatin interactions, DNA methylations, etc.
This FOA should be used when two or more collaborating sites are essential to complete the proposed research. It is required that the Research Strategy be identical across linked collaborative U01 applications, with the exception of a short section describing the specific function of each application under "elements unique to that site." For a linked set of collaborative U01 applications, each application must have its own Program Director/Principal Investigator (PD/PI) and the program must provide a mechanism for cross-site coordination. Applications that stand alone and are not collaborative should be submitted under the companion U01 FOA (PAR-17-257).
Projects awarded under this FOA and the companion FOA (PAR-17-257) will be governed by the PsychENCODE Consortium Executive Committee to facilitate and accelerate scientific progress through the coordination of research strategies, analytical methods, and data.
April 18, 2017
June 6, 2017
30 days prior to the application due date
July 6, 2017, June 6, 2018, June 6, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.
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.
Not Applicable
October 2017, October 2018, October 2019
January 2018, January 2019, January 2020
April 2018, April 2019, April 2020
June 7, 2019
Not Applicable
It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Part 1. Overview Information
Part 2. Full Text of the Announcement
Section
I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission
Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
Recent advances in human genetics are reshaping our understanding of the genetic architecture of mental disorders and their molecular pathophysiology. We now have a large number of significant replicable genetic signals associated with all major mental disorders including schizophrenia, bipolar disorder, and autism spectrum disorder. Many of the genetic signals contributing to disease risk are enriched in non-coding regulatory regions of the human genome. Additionally, psychiatric disorders, such as schizophrenia and autism spectrum disorder, are generally thought to result from dysfunction of neuronal circuitry involving multiple cortical and subcortical regions with disparate temporal, spatial, and cell-type specific etiologies. However, there is little or no data regarding network regulation of transcripts that span multiple developmental time periods, brain regions, and/or cell types in psychiatric disorders and associated dimensional and behavioral phenotypes. To gain insights into the molecular mechanisms underlying psychiatric disorders, it is critical to generate, integrate, and analyze data from multiple sets of comprehensive molecular profiles across brain areas and cell types in both diseased and healthy control brains. In addition, integrative multi-level analyses of multi-modal data that contains distinct biological information may facilitate the identification and prioritization of potential genetic targets and lead to drug discovery for these psychiatric disorders.
The PsychENCODE consortium (PEC), whose core projects resulted from the original Funding Opportunity Announcement (FOA), represents the largest integrative and collaborative effort in the field, with the common goal of mapping genomic regulatory elements on multiple molecular scales and developing molecular models of disease. Eventually, the PEC aims to generate spatio-temporal reference maps of functional genomic elements affecting human brain function and create a public resource of multidimensional genomic data. The PEC members are also collaborating with the Genotype-Tissue Expression project (GTEx), the Encyclopedia of DNA Elements (ENCODE), and other related consortia to enhance the power and impact of these analyses.
The PEC is making substantial headway and is actively sharing the resources that are being generated within the research community through the NIMH repository. However, progress in this area is only just beginning and much work is still needed to comprehensively characterize the functional diversity of genetic regulation in the brain at various genomic scales. Many regulatory elements are only functionally active in restricted cell contexts and/or specific developmental time periods, and only a small fraction of these cell types and periods (e.g. neurons, DLPFC, adult) are currently being studied. Through this FOA, the NIMH seeks to expand upon the ongoing efforts of the PEC to move towards a comprehensive functional characterization and deep molecular understanding of the brain. This goal will be achieved through new analyses and the production of new data on previously uncharacterized regions, cell types, and samples. A knowledge base of molecular information with spatial and temporal resolution across multiple domains is needed to elucidate the regulatory mechanisms and molecular networks that drive critical neurobiological processes involved in brain development and function, as well as dysfunction in psychiatric disorders.
This FOA will support research in the discovery and characterization of the full spectrum of non-coding functional genomic elements (e.g., enhancers, promoters, silencers, non-coding RNAs, chromatin interactions) across brain regions, cell types, and developmental time periods to elucidate their role(s) in the molecular pathophysiology of mental illness through genome-wide examination of various human cell and tissue sources (e.g., human brain). Applicants should propose projects that employ unbiased, cutting-edge, state-of-the-art, and high throughput genome-wide approaches, computational methods, and experimental assays using appropriate cells or tissues derived from patient populations to correlate findings with the development of mental illnesses and outcomes relevant to brain function. Another focus of this FOA is to support the identification of human-specific functional regulatory elements, preferably in different neural and glial cell types across brain regions in patient populations. Preference will be given to projects which are proposed by a highly interactive and synergistic team of investigators with complementary expertise. Successful applications will include expertise in genetics, neuro-developmental biology, psychiatry, high-throughput analyses, whole genome sequence analysis, computational bioinformatics, and/or other fields relevant to the FOA.
The scope of the projects proposed by applicants for this FOA should build upon the efforts currently supported by the PEC. For more details on the current PEC efforts, applicants should consult the PsychENCODE Knowledge Portal at psychencode.org. Applicants are strongly encouraged to include assessments of: 1) key developmental time periods, particularly the early post-natal and adolescent periods; 2) different neuronal and glial cell types/subtypes or cell lineages in brain regions implicated in molecular pathophysiology of psychiatric disorders where data is currently limited. Applicants are especially encouraged to propose assays that will explore classes of functional elements where information is currently scarce (e.g., chromatin conformation, transcription factor binding, single-cell analyses etc.) in order to gain a deeper understanding of the cell-type specific genetic regulatory architecture in human brain. Critically, the proposed research should be complementary to, and not duplicative of, the current efforts in PEC.
The specific areas of interest for this FOA include, but are not limited to:
1) Different classes of non-coding RNAs (long non-coding RNAs, microRNAs, piwiRNAs, etc.) and RNA modifications
2) Range of functional DNA elements (e.g., promoters, enhancers, silencers, insulators, transcription factor binding sites, RNA binding protein sites, etc.) and DNA methylation
3) Long-range chromatin interactions, chromatin conformation, and chromatin states
4) Proteomic changes
5) Various genetic alterations (e.g., single nucleotide variants, copy number variants, structural variants, etc.) identified from high-depth, whole genome sequencing.
Applicants are expected to utilize unbiased state-of-the-art genomic approaches for data generation. Applicants are strongly encouraged to combine/integrate data generated by the PsychENCODE consortium, both newly generated and existing datasets, with data from GTEx , BRAIN cell census, and other consortia (e.g., Brainspan, CommonMind, ENCODE, Common Fund Epigenomics, Roadmap Epigenome Mapping Consortium [REMC], and the International Human Epigenome Consortia [IHEC], GENCODE, 1000 Genomes, Psychiatric Genomic Consortium, Autism Sequencing Consortium) to examine cellular and tissue heterogeneity in genetic regulation. Applicants should propose studies involving human cells/tissues, leveraging existing human brain collections that include the brains of patients with psychiatric disorders wherever possible, and studies should have a rationale for the selection of such cells/tissues, including the extent to which they can potentially elucidate the pathophysiology of mental disorders.
Applicants should develop milestones to ensure progress on the specific aims of the project. Milestones are goals that should include clear and objective criteria for success. Applicants are required to outline biannual milestones to provide clear indicators of a project s continued progress or developing difficulties.
Milestone descriptions may include, but are not limited to:
The milestones should be regarded as criteria for evaluating the progress and direction of the Research Project, and should not be just a restatement of the specific aims.
Projects awarded under this FOA and the companion FOA (PAR-17-257) will be governed by the PsychENCODE Consortium Executive Committee to facilitate and accelerate scientific progress through the coordination of research strategies, analytical methods, and data.
Protection of Human Subjects: Applications with data collection plans that involve multiple respondent groups (e.g., clients/patients, therapists/providers, supervisors, administrators) should address provisions for human subject protections and consenting procedures for all participant groups accordingly. The NIMH has published updated policies and guidance for investigators regarding human research protection and clinical research data and safety monitoring (NOT-MH-15-025). The application’s Protection of Human Subjects section and data and safety monitoring plans should reflect the policies and guidance in this notice. Plans for the protection of research subjects and data and safety monitoring will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations.
See Section VIII. Other Information for award authorities and regulations.
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. See Section VI.2 for additional information about the substantial involvement for this FOA.
New
Renewal
Resubmission
Revision
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Clinical Trials Not Allowed for due dates on or after January 25, 2018: Only accepting applications that do not propose clinical trials
Need help determining whether you are doing a clinical trial?
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Application budgets are not limited, but need to reflect the actual needs of the proposed project.
The total project period for an application submitted in response to this FOA may not exceed 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
o Hispanic-serving Institutions
o Historically Black Colleges and Universities (HBCUs)
o Tribally Controlled Colleges and Universities (TCCUs)
o Alaska Native and Native Hawaiian Serving Institutions
o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to
apply.
Foreign components, as defined in
the NIH Grants Policy Statement, are allowed.
Applicant Organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Email: nimhreferrral@mail.nih.gov
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed with the following modifications:
Descriptive Title of Applicant's Project: To allow NIH to identify a group of applications as a related set of collaborative applications, the titles for each application in the set must have the following format: a 1/N indicator + Identical Title (e.g., 1/3 , where the 1/3 means this is site 1 of 3 sites in the set. The other sites will be labeled 2/3, etc.) Titles may not exceed 200 characters in length, including the tag, e.g., 1/3, at the beginning of the title.
Cover Letter Attachment: The Cover Letter is one pdf file only. The following collaborative information is required in the Cover Letter: a listing of all the applications that are a part of the set of collaborative applications being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., 1/3 ), and 3) the Applicant Institution. Each site should submit an identical listing.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Facilities and Other Resources:
Each application in a set of linked collaborative U01s must describe the facilities and resources available for that application. It is expected that this section of the application will be different in each of the linked applications. Applicants should especially focus on the unique resources at their institution and any sub-contracts which lend themselves to the completion of the project.
Other Attachments:
1. Project Management Plan
Linked applications must provide an identical Project Management Plan across sites, submitted as a single pdf attachment with the title "Project Management Plan."
Provide a plan detailing the measures that will be taken to ensure cross-disciplinary communication and integration across the team (i.e. the collaborating laboratories) and addressing the division of labor across the team. The Project Management Plan must provide a detailed description of how different elements of the project would operate in a synergistic and integrated manner, including a data coordination plan. The following guidelines and framework must be followed in developing this plan:
2. Milestones and Timeline Plan
Linked applications must provide an identical Milestones and Timeline Plan across sites, submitted as a single pdf attachment with the title Milestones and Timeline, that includes the following information:
Describe a timeline (Gantt chart) for completion of project aims, including unambiguous, quantifiable, and scientifically justified biannual milestones to provide clear indicators of a project’s continued progress or developing difficulties. Milestone descriptions may include, but are not limited to:
The milestones should be regarded as criteria for evaluating the progress and direction of the Research Project, and should not just be a restatement of the specific aims.
3. Data and Samples Plan
Linked applications must provide an identical Data and Samples Plan across sites, submitted as a single pdf attachment with the title Data and Samples Plan, that includes the following information:
Provide a detailed description of any available data and/or samples that will be leveraged for this project, including amounts, quality, type, location, procedure for acquiring, etc.
All instructions in the SF424 (R&R) Application Guide must be followed. It is expected that the projects will include synergistic research teams comprised of outstanding scientists from diverse scientific disciplines with expertise in neurodevelopment, genetics, psychiatry, computational bioinformatics, analysis of genome-wide data, high-throughput technologies, and/or other fields relevant to the FOA, as well as expertise in understanding the complexities of psychiatric genomics. As appropriate, Senior/Key Personnel should demonstrate their experience and expertise in these areas
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims:
The collaborative mechanism requires an Overview section as part of the specific aims attachment. This attachment must provide: 1) an overall rationale for applying as a collaborative study; 2) outline the role of each site and how they will contribute to achieve the FOA objectives; 3) Specific Aims of the collaborative project. This Specific Aims attachment must be identical in each of the applications that are linked together in a collaborative U01 set.
Research Strategy
Applications from each site must contain a Research Strategy that clearly describes those aspects of the project that are common to all sites of the linked applications.
The Research Strategy must be identical across linked collaborative U01 applications, with the exception of the section under the header "Elements Unique to This Site." All variations in the Research Strategy between sites, no matter how minor, should be highlighted in a subsection of the Research Strategy with the heading "Elements Unique to This Site" (estimated to be no more than 1 page of the Research Strategy Section). In this subsection, PDs/PIs should describe, for example, how the research site has a unique role in the collaboration, such as data coordination, statistical analyses, etc. Any site that contracts out some portions of this work should list this fact under "Elements Unique to This Site," and provide a full description of the nature, purpose, and oversight of this contractual arrangement.
Applications must conform with current guidelines, taking care to address important elements related to Significance, Approach, and Innovation.
Applicants are requested to clearly address the following aspects:
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
Appendix:
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.
When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Delayed Onset Study: All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Participation of NIH Intramural Scientists:
An NIH Intramural scientist may serve as a co-investigator, collaborator, or consultant. However, an Intramural scientist may not receive salary, equipment, supplies, or other remuneration from awards resulting from this FOA. The Intramural scientist must obtain written approval from his/her NIH Institute Scientific Director for the amount of resources that may be allocated to the project. The approval must also specify that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable), and with the PHS policy on vertebrate animal research. The participation of an Intramural scientist is independent of, and unrelated to, the role of the NIMH Project Scientist. The involvement of Intramural scientists needs to be consistent with NIH Policy and all applicable federal laws and regulations: https://oir.nih.gov/sites/default/files/uploads/sourcebook/documents/ethical_conduct/guidelines-conduct_research.pdf.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.
In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at NIMHReferral@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.
Applicants are required to follow the instructions for post-submission materials, as described in the policy.
Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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? How effectively will the project use comprehensive genome-wide approaches to expand our knowledge of the potential role of non-coding elements in the development of serious mental illnesses? To what extent does the application address exploring and establishing a comprehensive landscape of multi-modal molecular alterations across brain regions of patients with psychiatric disorders, and developing molecular models of those disorders? To what extent are the plans sufficiently bold to constitute a substantial advancement in the ability to generate, integrate, and analyze multi-modal molecular datasets (e.g., genomic, transcriptomic, epigenomic, proteomic, epitranscriptomic, chromatin architecture, etc.) to build comprehensive molecular models that will provide transformative insights into the molecular networks and complex pathways that confer susceptibility to psychiatric illnesses?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? To what extent do the PD(s)/PI(s) and other key personnel have adequate expertise in genetics, neurodevelopment, neurobiology, psychiatry, computational and bioinformatics methodologies, analysis of genome-wide data, protein biochemistry, and/or other fields relevant to the project, as well as expertise and understanding of the complexities of psychiatric genomics? To what extent are the track records of the PD(s)/PI(s) and other key personnel in the production and analysis of high-throughput multi-omic data adequate to conduct the proposed research successfully?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? To what extent does the project propose to include tissues, regions, cell types/subtypes, and key developmental time points under-represented in current studies and databases? Does the project adequately address issues of statistical power? Does the project include cutting-edge, unbiased genomic and computational approaches for data processing, quality control, integration, and multi-level analyses of diverse data types to build comprehensive molecular models of psychiatric phenotypes? Does the application propose adequate and robust plans for accurate annotation of DNA/RNA sequence to minimize false positives? Does the application utilize robust, well-validated, cost effective, scalable, and high-throughput techniques and methods? Does the proposed project address DNA/RNA sequencing read length and depth, and dynamic range for protein expression to detect and catalogue the full spectrum of genomic, transcriptomic, epigenomic and proteomic variations in healthy and diseased brains? Does the application describe plans for adopting and following the standards and protocols established by ENCODE, REMC, and the International Human Epigenome Consortium whenever possible? Are key technical barriers and dependencies identified?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Project Management Plan
Does the research plan justify the need for a collaborative multi-site project using this FOA? Is the Project Management Plan adequate and appropriate to ensure coordination of the different elements of the project? To what extent would this plan ensure that all elements would operate in a synergistic and integrated manner within and across sites? To what extent does the plan include adequate procedures to assure reliability and quality control, comprehensive transparency of data reporting, and sharing of resources? To what extent does the application include adequate plans for maintenance of close collaboration and effective communication among members within and across application sites? To what extent are the plans for data standards and data integration adequate to the need of the project? To what extent are adequate plans presented for the completion of the project following the loss of a key member of the group? Does the application describe processes for joint decision-making regarding research activities and publication, as well as procedures for resolving disagreements and grievance?
Milestones and Timelines Plan
Does the project propose realistic timelines and milestones? To what extent do the milestones adequately encompass all critical aspects of the project?
Data and Samples Plan
Are all proposed uses of existing data and samples adequately described?
For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
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.
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
For Renewals, the committee will consider the progress made in the last funding period.
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate, and whether substantial changes are clearly evident.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States, or augment existing U.S. resources.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIMH, 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:
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Mental Health Council. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.
For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
Cooperative Agreement Terms and Conditions of Award
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.
All awardees under this FOA and the companion FOA (PAR-17-257) will be governed by the PsychENCODE Consortium (PEC) Executive Committee composed of the PDs/PIs of each project within the network, NIMH Project Scientist(s), and the NIMH Program Officer to assist in monitoring and developing scientific content and direction of the program.
The PD(s)/PI(s) will have the primary responsibility to:
Ownership of all analytic tools, protocols, and assays developed during the course of the research rests with the respective PI(s) who generated them.
The Awardee Institution, and/or Research Project Leader's Institution, will retain primary custody of, and have primary rights to, data as specified under the NIMH approved data and research resource sharing plans (described above). The Government, via the NIMH Project Scientist(s), will have access to data generated under this cooperative agreement and may periodically review the data consistent with current DHHS, PHS, and NIH policies.
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The NIMH Project Scientist (or designated alternate in the event that the Project Scientist is not available) will have substantial programmatic/scientific involvement to:
In addition, a NIMH Program Officer has the usual stewardship responsibility for monitoring the conduct and progress of the project to ensure milestones are accomplished in accordance with the timeline. The Program Officer carries primary responsibility for periodic review and approval of the study protocol in relation to stated recommendations regarding continuance of the project, receives all required reports, determines that satisfactory progress is being made, and attends the PEC Executive Committee meetings as a non-voting participant. The Program Officer negotiates throughput, quality control, validation, and cost goals with the awardees as necessary, and suggests reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not being met, and may recommend withholding of support, suspension, or termination of a U01 award for lack of adherence to required policies and/or procedures.
Areas of Joint Responsibility include:
All awardees under this FOA will be governed by the PEC Executive Committee composed of the PDs/PIs of each grant, NIMH Project Scientist(s), and the NIMH Program Officer to assist in monitoring and developing scientific content and direction of the program. The PEC Executive Committee will select, by majority vote, a Chair from among the PD/PIs for a two-year term.
The PEC Executive Committee will:
It is expected that decisions made, or actions taken, by the PEC Executive Committee will be by consensus, or majority vote when needed; each project (project being either a single U01 supported under PAR-17-257 or a collaborative U01 set supported under this FOA) will have one vote in PEC Executive Committee decisions, with the NIMH Project Scientist (or alternate) having one vote. The NIMH Program Officer will not have a vote. All PEC Executive Committee members will attend at least one annual meeting in person to discuss progress and share research findings. Outside consultants/experts may be asked to participate in PEC Executive Committee meetings and discussions, but will not have a vote on committee decisions. Membership on the PEC Executive Committee becomes effective upon issuance of the Notice of Grant Award. The PD/PIs agree to accept the close coordination, cooperation, and participation of a NIMH Project Scientist and the Executive Committee to facilitate coordination of all U01 awards under this initiative.
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 Executive Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons
registration, submitting and tracking an application, documenting system
problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Grants.gov
Customer Support (Questions
regarding Grants.gov registration and submission, downloading forms and
application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov
GrantsInfo
(Questions regarding application instructions and process, finding NIH grant
resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573
Geetha Senthil, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-402-0754
Email: senthilgs@mail.nih.gov
Nick Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: nick.gaiano@nih.gov
Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: tjarosik@mail.nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.