National Institutes of Health (NIH)
Study of Nuclear Bodies and Compartments (U01)
U01 Research Project – Cooperative Agreements
RFA-RM-14-006, U54 Specialized Center - Cooperative Agreements
RFA-RM-14-007, U01 Research Project - Cooperative Agreements
RFA-RM-14-009, U01 Research Project - Cooperative Agreements
RFA-RM-14-010, U01 Research Project - Cooperative Agreements
RFA-RM-14-011, U01 Research Project - Cooperative Agreements
The purpose of this FOA is to support projects to develop tools and strategies for studying: 1. the three dimensional architecture of the nucleus in relationship to the topography of nuclear bodies and transcriptional machineries, 2. the structure and function of poorly characterized nuclear structures, or 3. the role of specialized proteins and RNAs in the assembly, organization, and function of nuclear bodies, nuclear structures, and specialized subnuclear domains.
September 24, 2014
January 2, 2015
January 2, 2015
February 2, 2015, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.
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.
February 3, 2015
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.
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
It has been more than a decade since the human genome was completely sequenced. Despite vastly improved technologies and many important foundational discoveries, our understanding of how genomic information specifies proper execution of spatial and temporal gene expression programs remains to be fully elucidated. This knowledge is essential for understanding how cells divide or respond to their environment, for identifying the regulatory mechanisms that control development and are dysregulated in disease, and for studying phenotypic variations among human populations. It is now clear that while mammalian genomes encode genetic information in their linear sequence, the appropriate cell type specific expression of their genes depends on higher order nuclear organization, from the folding of chromosomes into three-dimensional structures, to chromatin loops that connect genes and transcriptional regulatory complexes, to larger chromosomal domains and nuclear compartments. Defining chromatin interactions and the ways in which nuclear architecture constrains/enables interactions, and describing the relationships of genomic regions to transcription, RNA processing and chromatin regulatory machineries, is likely to reveal how individual cells access, read and interpret genetic information. Because this spatial organization of genomes is dynamic, we also need to understand how it changes in response to environmental challenges and cellular processes such as cell cycle, differentiation, or neoplastic transformation. A comprehensive understanding of the contribution of the structural and functional organization of the mammalian genome to development and disease in both space (3D Nucleome) and time (4D Nucleome) will require major efforts.
The Four-Dimensional Nucleome (4DN) was selected by the NIH Leadership as the focus for a Common Fund Program following a series of discussions with panels of scientific experts and stakeholders, and with input from the broad community solicited via a Request for Information early in 2014 (NOT-RM-14-010). The impetus for its selection as a Common Fund program was the growing awareness that understanding the architecture of the cell nucleus may have widespread and profound implications for human health and disease, but our current ability to study nuclear organization is hindered by a number of outstanding technological and conceptual challenges.
Experts from the research community identified the following scientific priorities as areas that represent challenges and opportunities for investment by the NIH: 1) next-generation, high-resolution and high-throughput tools to explore the relationships between nuclear organization and the regulation of gene expression programs, including with single cell resolution; 2) computational tools to integrate existing data sets, and to manage, analyze, and visualize the datasets generated by a community effort; 3) predictive models of nuclear structure/function relationships in the context of various cellular states or transitions (differentiation, reprogramming, cell cycle, responses to external stimuli, disease development); 4) next-generation tools to explore nuclear dynamics through controlled disruption of nuclear conformation, and imaging in live cells and tissues; and 5) “pilot” maps (using in-development technologies) and “reference” maps (using robust and validated technologies) of the 3D architecture of the interphase nucleus for a variety of eukaryote cells and tissues;
The Common Fund 4DN Program has been developed to address these critical issues. The overarching goals of the 4DN Program are to understand the principles that guide the spatial and temporal organization of the nucleus, the role of this organization in orchestrating the transcriptional complexity in individual cells and tissues, and the way in which changes in nuclear organization affect development and disease processes. The Program consists of 6 initiatives, of which this FOA is one. Specifically, the initiatives are:
RFA-RM-14-006 Nuclear Organization and Function Interdisciplinary Consortium (U54)
RFA-RM-14-007 Nucleomics Tools (U01)
RFA-RM-14-008 Study of Nuclear Bodies and Compartments (U01)
RFA-RM-14-009 4D Nucleome Imaging Tools (U01)
RFA-RM-14-010 4D Nucleome Network – Organizational Hub (U01)
RFA-RM-14-011 4D Nucleome Network – Data Coordination & Integration Center (U01)
Awards funded under these FOAs are anticipated to pursue research activities conducted by multidisciplinary teams of investigators. In addition, all awardees from all 6 initiatives will form the 4DN Network, with the overarching goal of determining the fundamental principles of nuclear organization. Validation and comparisons across studies will be essential to establish these cross-cutting principles so investigators must be willing to work collaboratively as part of the Network.
This initiative is funded through the NIH Common Fund, which supports crosscutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite applicants to develop bold, innovative, and often-risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.
The spatial organization of the eukaryotic cell nucleus has emerged as a key determinant of genome function. Studies of how the nucleus is organized within the interchromatin space have revealed a complex and dynamic architecture that consists of numerous morphologically distinct structures or compartments, referred to as nuclear bodies. These include nucleoli, Cajal bodies (CBs), Polycomb group (PcG) bodies, splicing factor compartments, paraspeckles, promyelocytic leukemia (PML) bodies, perinucleolar compartments (PNCs), and many more. A better delineation of the 3D organization of the genome in the context of nuclear bodies and other subnuclear domains is essential to fully appreciate their role in regulating gene expression and function in the nuclei of normal and diseased cells. Recent studies have demonstrated that nuclear bodies and other specialized subnuclear domains can serve as reaction sites or hubs for modulation of nuclear processes such as transcription, epigenomic modification, gene silencing, and higher order chromatin organization, but details of their assembly and biological function are lacking. Understanding of the exact role played by different nuclear bodies and subnuclear domains will require the development of new technologies and approaches to study the detailed organization and function of specific structures within the nucleus.
Proposed projects must include the following: 1) the major thrust of the application should involve exploration of subnuclear structures, and 2) the application must include the development of a new tool or strategy or the significant improvement of an existing tool or strategy to investigate subnuclear structures. Applications lacking either of these elements will be deemed non-responsive to the FOA and will not proceed to review.
Relevant topics of investigation include the development of tools and technologies that improve or enable our ability to explore:
- The molecular components (RNA, protein, lipid, etc) of nuclear bodies and compartments which could include characterization of any associated post-transcriptional or post-translational modifications;
- Improvements in the purification of nuclear bodies and subnuclear structures;
- Strategies to correlate nuclear bodies with specific genomic regions or other subnuclear features;
- Improved ways to catalog the varieties and components of nuclear bodies and subnuclear structures within and between types of cells;
- The mechanisms by which transcription factors, chromatin features, or other relevant proteins and RNAs interact with or regulate nuclear bodies;
- The development of approaches to explore the composition and functions of nuclear bodies in single cells or using a limited number of cells;
- The function of nuclear bodies through the development of genome editing tools or small molecule modulators that perturb specific subnuclear structures;
- The temporal dynamics of nuclear body formation and maintenance in a specific cell and/or during the cell cycle;
- Whether or not nuclear bodies associate with specific alleles, gene loci or chromosomes.
When choosing cell systems or experimental platforms in response to this initiative, applicants may propose to use any eukaryotic model system for the proposed studies (plants, fungi, protists, invertebrates, vertebrates). However, applicants should describe how their tool or strategy would be applied to mammalian systems in the future.
Applicants are encouraged to develop high-risk, high-impact, broadly applicable technologies and analytical techniques enabling measurements that have not previously been possible.
To be responsive to this FOA, investigators must develop an approach for which the primary means of measurement does not rely on imaging technologies, although imaging studies can be used in the overall strategy to help with the development or validation of the new technology. Applicants proposing primarily to develop imaging strategies to explore nuclear bodies should apply to FOA RFA-RM-14-009. Applicants proposing primarily to develop tools or approaches to explore the function of regulatory RNAs and/or nuclear proteins in the organization of the mammalian genome beyond their role in the assembly, organization and function of nuclear bodies, nuclear structures or specialized subnuclear domains should consider applying to FOA RFA-RM-14-007. Applicants may request support for up to 5 years.
This FOA uses the U01 Cooperative Agreement mechanism. Successful applicants will become members of the larger 4D Nucleome Network composed of investigators who have been funded in response to at least one of the six related 4DN Network FOAs. In addition to completing the research goals outlined in their applications, successful applicants will be expected to work collaboratively with all members of the 4D Nucleome Network, including the 4DN Network Organizational Hub (RFA-RM-14-010) and the 4DN Network Data Coordination & Integration Center (RFA-RM-14-011), to help develop common standards, metrics for data generation and storage, and data analysis and visualization tools that can be used by the broader scientific community. The 4DN Network will encourage the initiation of new collaborative research projects across the entire network. Some of these interactions could be facilitated by an Opportunity Pool of funds that will be managed by the 4DN Organizational Hub and NIH Program Staff.
A key aspect of this program is the formation of a consortium-type partnership amongst all 4DN Network awardees. Shared responsibilities derived from the use of the Cooperative agreement mechanism are described later in this FOA, and will be further articulated during the kickoff meeting of the 4DN Network that will take place a few months after awards are made. All 4DN Network investigators will be required to attend this initial 4DN Kickoff meeting, as well as annual 4DN investigator meetings and regular teleconferences with Network members and NIH Staff for the duration of the funding cycle.
All applicants are strongly encouraged to contact NIH Staff to discuss the alignment of their proposed work with the goals of this FOA, and the 4DN Program. A Technical Assistance teleconference will be held for potential applicants. NIH staff will be available to answer questions related to this FOA. Time, date, and dial in information for the call will be announced in an NIH Guide Notice and will be posted on the 4DN website: http://commonfund.nih.gov/4Dnucleome/index.
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.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
The total amount of funds available is $3 million per year. It is anticipated that 5 -8 projects will be supported.
Although the financial plans of the NIH provides support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. Future year amounts will depend on annual appropriations.
Application budgets are not limited but need to reflect the actual needs of the proposed project.
The scope of the proposed project should determine the project period. The total award period requested for this FOA may not exceed five 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:
Nonprofits Other Than Institutions of Higher Education
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 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:
In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:
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.
It is critical that applicants follow the 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:
John Satterlee, Ph.D. (on behalf of the NIH Common Fund 4D Nucleome
National Institute on Drug Abuse/NIH
Division of Basic Neuroscience and Behavioral Research
6001 Executive Blvd. Rm 4101
Bethesda, MD 20892
(For Fedex Delivery the address is Rockville, MD 20852)
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.
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.
Budget requests must include costs for the PD/PIto attend the initial in-person 4DN Network kick-off meeting, and for the PI and up to three other members of the project team to attend the annual 4DN Network Investigator's meetings.
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: Describe how the current concepts, methods, or technologies in the field will be changed if the Specific Aims are achieved. Critically evaluate existing knowledge and approaches that have been or are being applied in this area of research and specifically describe how the proposed approach will advance the field. Key milestones, uniqueness of the team, and the expected outcomes of the project, if successful, should be clearly described.
Research Strategy: As part of the Research Strategy, applicants are asked to address the following points:
1) Significance: Explain the importance of the problem or critical barrier to progress in the field that the application is trying to address, and why the proposed approach or technology is needed to realize a solution. Explain how the proposed project will improve scientific knowledge or technical/experimental capability by providing new tools or data to the scientific community. State concisely the importance and relevance of the proposed research for the field. Applicants with very risky applications or that lack substantial preliminary data are encouraged to submit applications requesting a shorter project period (2 - 3 years). Applicants are expected to describe how the specific nature or performance of their proposed technology or experimental approach adds to currently available tools, and to detail the expected performance goals for their technology, including throughput, sensitivity, scalability, capacity for single-cell versus ensemble measurements, and ability to measure dynamic changes in mammalian genome organization.
2) Innovation: Innovation will be evaluated based on a coherent plan to deliver new knowledge and/or experimental capabilities to the scientific community. For example, for the purpose of this FOA it may be innovative to develop technologies or approaches that can help solve a recognized unmet need in our ability to understand the nuclear organization of mammalian genomes in relation to nuclear bodies and compartments. Innovation might be heightened by the development of tools and approaches that can be easily adopted into routine practice and will give users, for example biomedical researchers, new understanding not available from existing technologies. Identify the nature of innovations involved and explain their importance to the success and potential impact of the application. To the extent relevant, explain how the application challenges and seeks to shift current research paradigms. Describe any novel theoretical concepts, approaches or methodologies, instrumentation or intervention(s) to be developed or used, advanced system integration, and any advantage over existing methodologies or instrumentation. Explain any refinements, improvements, or new applications of theoretical concepts, approaches or methodologies, system integration, combinations, scale-up, instrumentation, or interventions.
3) Approach: Technical feasibility for the approach should be clearly established by preliminary results so that any risks present can be mitigated and alternative approaches proposed. Comparison of performance specifications with current practices is expected, such as sensitivity, specificity, reproducibility, reliability, portability, throughput, and operability by other biological researchers. Describe the overall strategy, methodology, and analyses to be used to accomplish the specific aims of the project. Discuss potential problems, alternative strategies, and benchmarks for success anticipated to achieve the aims. If the project is in the early stages of development, describe any strategy to establish feasibility, and address the management of any high risk aspects of the proposed work. An integrative systems approach or a design-driven approach and their appropriateness for the proposed project should be described, including plans for collecting, analyzing, interpreting, and archiving data. Details for making the performance of technologies sufficiently selective, sensitive, or otherwise appropriate for the identified problem should be supported with quantitative benchmarks. Potential technical challenges and possible alternative approaches to achieve the aims of the project should be discussed. The robustness and reproducibility of preliminary results should be described along with independent validation or replication of results if available. Alternative interpretations of preliminary data, including relevant literature in support or disagreement with the results, should be described. For projects that pursue feasibility in humans, the approach should describe contact with appropriate regulatory bodies and milestones for achieving regulatory approval. All projects should propose a plan for the biological validation of the new principles of nuclear organization resulting from the use of the proposed technology or experimental approach. Validation read-outs could include genome-wide transcriptomics, nuclear imaging endpoints, or measurements of key aspects of cell function. The biological relevance of new principles of nuclear organization could also be tested through controlled manipulation of defined structures or regulatory elements, or by following the establishment, maintenance, and dynamic changes of recorded organizational determinants in live cells, in the context of processes such as mitosis or changes in cell fate or cell function.
Project Timeline: A timeline (Gantt chart) including milestones is required for all studies. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Yearly quantitative milestones are required in order to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. Milestones and the timeline must be provided in a separate heading at the end of the Approach section.
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.
When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
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.
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). 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.
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.
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.
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 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. The intramural project should be added as a separate component to the parent application.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.
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? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific to this FOA: Will the proposed project significantly improve our understanding of nuclear bodies and their relationship to other subnuclear features? Will the proposed technologies and strategies enable the study of critical aspects of nuclear bodies and nuclear structures that cannot be adequately measured with existing technologies, or constitute an order of magnitude improvement on existing approaches in terms of throughput, sensitivity, scalability or cost? Will the project address a problem or critical barrier in understanding the structure or function of nuclear bodies in mammalian cells? What is the potential for the proposed approach to be widely adopted and easily used by the research community?
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?
Specific to this FOA: Does the project team have the appropriate experience for developing, optimizing, and validating the proposed technology and the related analytical and modeling tools in mammalian cells during the proposed funding period? Does the project team have a track record of disseminating novel tools and techniques broadly?
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?
Specific to this FOA: Does the application represent an innovative technological solution for studying nuclear bodies and/or subnuclear structures? If the applicant is proposing to improve an existing tool or strategy for investigating nuclear bodies and nuclear structures, will the improvement be significant or incremental?
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed?
If the project involves 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?
Specific to this FOA: How well does the proposed research utilize advances in our understanding of nuclear bodies and their relationship to other subnuclear features? Will the proposed technology receive adequate validation during the funding period, so that it can be adopted and used by the scientific community? Is the proposed research milestone driven with clear metrics and go/no-go decision points?
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?
Specific to this FOA: Is the proposed environment and team-structure likely to foster true multi-disciplinary collaborations in pursuit of developing and validating an innovative technology?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Protections for Human Subjects
For research that involves human subjects but does not
involve one of the six categories of research that are exempt under 45 CFR Part
46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Children
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 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.
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.
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.
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 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 submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to 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.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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 U01, 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. A Memorandum of Understanding (MOU) developed by the NIH Common Fund should serve as a guidance document to provide a framework under which relationships between investigators and NIH Program Staff are established. Templates for Confidential Disclosure Agreements (CDAs) and Collaborative Research Agreements (CRAs) have been developed by the NIH Office of Technology Transfer. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
Adherence to a 4DN Communication Plan:
A consensus 4DN Communication Plan will be drafted by the 4DN-SC during the kickoff meeting of the 4DN Network. This plan will clearly spell-out interactive requirements that all 4DN investigators are expected to follow, including:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Areas of Joint Responsibility include:
Disagreements that may arise in scientific/technical matters, publication/authorship matters or programmatic matters (within the scope of the award) between award recipients, or between award recipients and the NIH, may be brought to arbitration after first attempting to resolve the issue through the 4DN-SC or its subcommittees, as appropriate. An Arbitration Panel composed of three members will be convened. The Panel will be composed of: a designee of the 4DN-SC 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 members; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure in no way affects the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.
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.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
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)
Finding Help Online: http://grants.nih.gov/support/index.html
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
John Satterlee, Ph.D.
National Institute on Drug Abuse (NIDA)
David Balasundaram, Ph.D.
Center for Scientific Review (CSR)
National Institute on Drug Abuse (NIDA)
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.
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