Participating Organization(s) |
National Institutes of Health (NIH) |
Division of Program Coordination, Planning and Strategic
Initiatives, Office of Research Infrastructure Programs (ORIP) |
|
Funding Opportunity Title |
Improvement of Animal Models for Stem Cell-Based Regenerative Medicine (R01) |
Activity Code |
R01 Research Project Grant |
Announcement Type |
New |
Related Notices
|
|
Funding Opportunity Announcement (FOA) Number |
PAR-13-114 |
Companion Funding Opportunity |
PAR-13-115, R21 Exploratory/Developmental Grant |
Catalog of Federal Domestic Assistance (CFDA) Number(s) |
93.351, 93.847, 93.837, 93.121, 93.859, 93.846 |
Funding Opportunity Purpose |
This FOA encourages Research Project Grant (R01) applications from institutions and organizations proposing research aimed at characterizing animal stem cells and improving existing, and creating new, animal models for human disease conditions. The intent of this initiative is to facilitate the use of stem cell-based therapies for regenerative medicine. The initiative focuses on the following areas: 1) comparative analysis of animal and human stem cells to provide information for selection of the most predictive and informative model systems; 2) development of new technologies for stem cell characterization and transplantation; and 3) improvement of animal disease models for stem cell-based therapeutic applications. |
Posted Date |
February 11, 2013 |
Open Date (Earliest Submission Date) |
May 5, 2013 |
Letter of Intent Due Date(s) |
Not Applicable |
Application Due Date(s) |
Standard dates apply, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. |
AIDS Application Due Date(s) |
Not Applicable |
Scientific Merit Review |
Standard dates apply |
Advisory Council Review |
Standard dates apply |
Earliest Start Date |
Standard dates apply |
Expiration Date |
New Date February 9, 2016 per issuance of PAR-16-093. (Original Expiration Date: May 8, 2016) |
Due Dates for E.O. 12372 |
Not Applicable |
Required Application Instructions
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
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
This FOA encourages Research Project Grant (R01) applications from institutions and organizations proposing research aimed at characterizing animal stem cells and improving existing, and creating new, animal models for human disease conditions. The Division of Comparative Medicine (DCM) in ORIP and representatives from other NIH institutes convened an NIH workshop in 2012 that addressed the current status of animal stem cell biology and made recommendations concerning improvements in technologies and applications of animal stem cells to regenerative medicine (see http://dpcpsi.nih.gov/orip/documents/summary_of_the_improving_animal_models.pdf). The results of this workshop provide the basis for this FOA. The intent of this initiative is to facilitate the use of stem cell-based therapies for regenerative medicine. The initiative focuses on the following areas: 1) comparative analysis of animal and human stem cells to provide information for selection of the most predictive and informative model systems; 2) development of new technologies for stem cell characterization and transplantation; and 3) improvement of animal disease models for stem cell-based therapeutic applications.
Regenerative Medicine is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to damage or congenital defects. Regenerative medicine has the potential to solve the problem of the shortage of organs available for donation. It also holds the promise of repairing or replacing damaged tissues and organs in the body by stimulating organs previously considered irreparable to heal themselves. The recent discovery of the reprogramming of adult cells to a pluripotent state provides opportunities to address a major problem of regenerative medicine, immune rejection of transplanted tissue. The ability to generate differentiated cells and tissues using cells from specific patients will facilitate individualized medicine and eventually will lead to specialized therapies. The field is moving toward translation to clinical practice and is becoming increasingly dependent on animal models and information regarding the potential therapeutic efficacy of new technologies. Generating the correct type and quantity of the specific cell types required for replacement therapy is a significant challenge, as are the problems associated with introducing these cells into the proper environment in vivo and overcoming immune reactions. Finding solutions to these problems will require extensive testing in experimental animal models.
Major advances have been made in the past several years in deriving pluripotent cells, such as embryonic stem cells (ESCs) and induced pluripotent cells (iPSCs) from both humans and animals. In parallel, other investigations have isolated and characterized multipotent somatic or adult stem cells from various tissues, including Mesenchymal Stem Cells (MSCs) and Germinal Stem Cells (GSCs). The discovery of mouse ESCs in 1981 revolutionized the field of developmental biology and provided new capability for genome manipulation and investigations of gene function. Isolation of human ESCs created new possibilities for the field of regenerative medicine. ES-like cells have been derived from a number of animal species, including rats, fish, cows, pigs and non-human primates. Many characteristics of animal ES-like cells, including surface markers, growth factor requirements, ability to differentiate and others can be quite different from human ESCs.
The field of stem cell research experienced a dramatic new direction with the isolation of induced pluripotent stem cells (iPSCs), derived by reprogramming somatic cells to a pluripotent state. Several studies on various animal systems suggest that the basic pluripotency network appears to be conserved among different species, allowing derivation of iPSCs from a variety of animals.
MSCs, a type of somatic stem cell, were originally identified as a subpopulation of bone marrow cells with osteogenic potential. The properties of MSCs have been examined extensively over the past decade. Studies using animal models have shown promising results following MSC therapy for induced injury in the musculoskeletal, cardiovascular, digestive and nervous systems. In addition, many clinical trials have demonstrated the efficacy of MSC infusion for treating various human diseases. Given the wide range of tissue sources, the recognition of subpopulations with specific properties, and the frequent production of genomic alterations upon expansion in cell culture, extensive characterization of MSCs and development of improved techniques are required. Most importantly, there is relatively limited understanding of the normal biological functions of MSCs and the mechanisms by which they participate in tissue repair.
GSCs are another type of somatic stem cells of great interest for regenerative medicine. They are an essential component of reproductive biology. Genetic manipulation of GSCs provides a powerful tool for producing transgenic animals, for elucidating mechanisms underlying germ cell development and differentiation and for understanding the interactions between stem cells and their niche. Further development of the methods for unlimited production of GSCs (for producing either sperm or eggs) will impact the ability to investigate the molecular basis of germ cell differentiation and for treatment of infertility by transplantation. Numerous reports using animal and human GSCs have shown generation of pluripotent cells during in vitro cultivation, which potentially can solve a number of issues. However, it remains difficult to isolate, derive and maintain stable cultures of these cells from humans and animals. Furthermore, the mechanisms that determine the reprogramming of GSCs into pluripotent stem cells are not well understood and efficient methods for directed reprogramming of these pluripotent stem cells still have to be developed.
Along with rodents, several other animal species are being developed as models for various studies in the field of regenerative medicine. Understanding the properties and capabilities of stem cells derived from animals such as rabbits, pigs, sheep, goats and monkeys will increase the potential for the use of the most appropriate systems for modeling particular human disease conditions or for other medical applications. Non-rodent species (often referred to as large animal models ) provide important advantages for transplantation studies, including large size, similarity to human physiology and pathology and longer life span, thus facilitating translation to studies in humans. The use of animal stem cells as a model for human cells in procedures related to regenerative medicine requires in-depth understanding of common regulatory pathways and species-specific properties and their impact on potential therapeutic applications.
Animal experiments have historically made a significant contribution to understanding human disease. However, animal studies need to be improved in order to better predict the effectiveness of treatment strategies in clinical trials. Several possible causes of the disparity between the results of animal studies and clinical trials have been identified, including failure to acknowledge the limitations of animal models, inadequate animal data and conclusions from them, less than optimal disease models and overestimation of treatment efficacy due to the preferential publishing of positive results, relative to negative results. These problems should be addressed in the design and execution of preclinical, animal-based studies involving stem-cell based therapies.
The research activities specific to each of the participating Institutes and Centers (ICs) are discussed below. While the objectives of the application must be in accord with the specific interests of the ICs listed below, applications submitted for funding consideration by ORIP may be of a more general nature and should involve activities that are relevant to the interests of two or more of any of the categorical NIH Institutes and Centers. Specific interests of the sponsoring Institutes and Centers are as follows:
Projects supported by ORIP under this FOA are intended to improve existing and create new animal models for regenerative medicine. Preference will be given to investigations that examine general principles involved in developing the most informative animal models for regenerative medicine, rather than focusing on a specific disease. However, investigations involving specific diseases can be used as proof of principle. In all cases, for funding consideration by ORIP, the potential results of investigations should be applicable to the interests of two or more of any of the categorical NIH ICs. Furthermore, investigations of a disease that predominantly relates to the interests of one NIH IC and peripherally relates to the interests of other NIH ICs are not appropriate for ORIP funding. The ultimate objective of these efforts should be to provide essential preclinical knowledge that can help inform future clinical investigations.
The following are examples of research topics of particular interest to ORIP. Other innovative concepts are also encouraged.
- Characterization and enhancement of animal stem cells as model systems for human stem cells. Innovative approaches to understand the biology of stem cells from species widely used in regenerative medicine. Rat stem cells are of particular interest, taking into account current advances in isolation and characterization of stem cells from rats, the progress of the rat genome project and current advances in the ability to manipulate rat genes.
- Development and characterization of stable, well characterized pluripotent stem cell lines from large animal species, such as rabbits, dogs, pigs, sheep and monkeys. Development of stem cell lines from this type of animal model should be justified as having direct relevance to potential uses in the field of regenerative medicine. Creation of biomarkers, standard protocols, species-specific reagents, proteomics, transcriptomics and genetic tools to assist the use of these cells is also of interest.
- Comparative analysis of animal and human stem cells to define criteria that will assist in choosing the most appropriate animal species and stem cell type for a particular application.
- Development of new techniques for: Guiding and verification of the accuracy of cell injection, tracking cell migration, evaluating off-target effects, and monitoring long-term integration and the phenotype and function of transplanted stem cells and their derivatives.
- Development of new approaches to: Understand and target the cell-fate-determining niche to improve extrinsic effects on stem cell function; increase cell survival and proper integration into the host environment; establish correct regulatory connections after cell-grafting experiments.
- Investigations of the therapeutic benefits of human and animal MSCs in animal models and mechanisms of their biological action. Improvement of methods for testing the efficacy and potency of MSCs in animals and for controlling the MSC secretome post-transplantation. Development of definitive markers for the multipotent state of the cells. Investigations of the cause of the high sensitivity of MSCs to the microenvironment. Standardization of culture conditions for scale up of production.
- Investigations of animal GSCs as models for understanding embryogenesis and organogenesis, stem-cell niche interactions and fate decisions. The focus should be on facilitating the application of GSCs for regenerative medicine, for example, exploring the potential for generating pluripotent cells and for deriving genetically modified animal models, including the use of haploid cells for this purpose. Preference will be given to applications working with large animal models, such as rabbits, dogs, pigs, sheep and monkeys.
- Investigations to improve existing humanized animal models and create new ones. Preference will be given to studies involving species other than rodents. Of particular interest are advances in the reproducible and cost-effective generation of humanized chimeras, which is currently technically challenging. Development of humanized animals for in vivo generation of complex human tissues and organs using stem cells.
- Development of high throughput genetic and therapeutic screens to study stem cell biology and homeostasis in appropriate animal species, such as Drosophila and zebrafish.
- Improvement of animal disease models for regenerative medicine, which will better emulate physiological, cellular and molecular manifestations seen in humans. Development of methods to increase the predictability of stem cell based treatments in regard to effectiveness, major complications, safety and off target effects. Demonstration of the functionality of specific stem cells or their derivatives and the effectiveness of achieving specific results in improved animal disease models.
- Investigations of mammalian stem cell reprograming and somatic cell transdifferentiation. Further development of approaches and protocols for manipulating cell fate using efficient and safe methods, including removable vectors and vector systems with temporal expression of transcription factors, RNA or small molecules. Determination of how these modifications can be used to control the expansion and differentiation of resident progenitor cells for direct reprogramming in vivo.
- Development of animal models for effective and sustained gene-therapy using ex-vivo engineered stem cells and their derivatives as well as endogenous stem cell populations to correct gene defects. Preference will be given to applications that provide general approaches for a broad array of uses. Proposals should not be focused on therapy for specific diseases. However, a specific disease can be used as a proof of principal, if also applicable to other disease conditions. Improve and study the safety of newer technologies such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), allowing targeted approaches for the elimination of disease-causing mutations, as tested in animal models.
- Development of solutions to problems of stem cell therapy that have already been identified, such as: Heterogeneity of cell populations, genetic instability, high mutation rate during in vitro manipulations, epigenetic memory of differentiated iPSCs and immune responses induced after stem cell transplantation. Of particular interest is the development of functional assays and high-throughput techniques that will predict the potential immunogenicity of transplants and the tumorigenicity or metastatic potential of stem cell lines.
- Development of new methods or animal models to evaluate the safety of stem cell transplantation in animals, including studies of adsorption, distribution, metabolism, excretion and toxicity of stem cell-based therapeutic products. These models should take into account properties of the specific stem cell populations and should mimic the intended use of the cells in humans.
The National Heart, Lung, and Blood Institute (NHLBI) is interested in the above listed research topics as applied to the following mission areas of the Institute: i) stem cell engineering and regeneration of complex heart, vascular, lung, and blood systems; ii) stem cell correction of either congenital or acquired heart, lung and blood defects, iii) stem cell regeneration/reconstruction of heart, lung, and blood tissue; and iv) optimization of the host’s microenvironment to improve the survival and function of transplanted HUMAN heart, vascular, lung, and blood tissues, including but not limited to, in vivo models that aim to overcome immunological/ex vivo manipulation/tumorigenic safety concerns associated with FDA regulatory requirements. Preference will be given to in vivo models developed using NHLBI resources (e.g., Production Assistance for Cellular Therapies (PACT), Science Moving towArds Research Translation and Therapy (SMARTT), Gene Therapy Resource Program (GTRP). NHLBI has interest in the development of new in vivo models for health and disease, particularly large animal models such as sheep, pig, dog and non-human primates, to overcome the unique dynamics of heart, lung, and blood systems, which can be scientifically justified. New models should include in their research plan validation studies for the purpose of preclinical experiments that may lead to an Investigational New Drug (IND), Investigational Device Exemption (IDE) or similar regulatory approval. NHLBI does not have interest in applications proposing mechanistic studies on mouse models.
The National Institute of Dental and Craniofacial Research (NIDCR) will support projects which relate to the major mission of the institute, to improve oral, dental and craniofacial health through research, research training, and the dissemination of health information. The following are examples of potential research topics, though other related innovative projects are also encouraged:
- Development of human disease- and injury- relevant animal models for tissues of oral and craniofacial complex. Projects utilizing both small and large animal models should be solicited, but preference should be given to large animal models, including humanized large animal models.
- Development and validation of predictive in vivo assays for testing safety and efficacy of tissue engineering and regenerative medicine-based therapies using clinically-relevant readouts and end-points with a particular emphasis on assays large animal models.
- Development of multi-prong strategies and tools for successful structural and functional integration and long-term function and survival of regenerated tissues in animal models. These include: modulating disease- and injury-related infection, inflammation and tissue destruction, optimizing graft biocompatibility and preventing graft-related pathological responses, and building and rebuilding structural and functional interfaces between the regenerated and host tissues.
- Development of new strategies for regeneration of composite multi-tissues with a particular emphasis on those in large animal models.
- Validation, standardization and comparative analysis of different stem and progenitor cell sources, scaffolds and biomaterials for optimal regeneration of oral and craniofacial tissues.
- Development of efficient and controlled in vivo biomolecule-, gene- and cell- delivery strategies to tissues of oral and craniofacial complex with a particular emphasis on delivery in large animal models.
- Development of sensitive, high-resolution in vivo cell tracking and imaging modalities as well as cell and tissue labeling and quantitative image analysis tools for tissues of oral and craniofacial complex with a particular emphasis on live longitudinal cell tracking and imaging in large animal models.
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is interested in applications conducting basic and translational research that will facilitate the use of stem cell-based therapies for diseases/conditions in the NIDDK mission, including: Type 1 and Type 2 Diabetes, obesity, endocrine and metabolic diseases, kidney and urologic diseases, hematologic diseases, and digestive diseases (including liver disease).
Of particular interest are projects within these disease areas focused on:
- improving animal disease models for testing stem cell-based therapeutics;
- comparative validation of stem and progenitor cell sources for translational use;
- engineering approaches designed to monitor and improve stem cell function in vivo;
- methods to enhance delivery and maintenance of cell-based therapeutics.
The National Institute of General Medical Sciences (NIGMS) welcomes projects that are relevant to the Institute's mission: basic scientific research that increases understanding of life processes and lays the foundation for more applied advances in disease diagnosis, treatment, and prevention. NIGMS is interested in research on fundamental aspects of pluripotent stem cells, such as self-renewal, pluripotency, reprogramming, differentiation capability, and niche-stem cell interactions. Comparative studies between human and animal stem cells with respect to these properties would be appropriate, particularly those addressing mechanistic questions.
Funding Instrument |
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. |
Application Types Allowed |
New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. |
Funds Available and Anticipated Number of Awards |
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. |
Award Budget |
Application budgets are not limited, but need to reflect actual needs of the proposed project. |
Award Project Period |
The scope of the proposed project should determine the project period. The maximum award period is 4 years for ORIP/DPCPSI and 5 years for NHLBI, NIDCR, NIDDK and NIGMS. |
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
- Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
For-Profit Organizations
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
Governments
- State Governments
- County Governments
- City or Township Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
- Eligible Agencies of the Federal Government
- U.S. Territory or Possession
Other
- Independent School Districts
- Public Housing Authorities/Indian Housing Authorities
- Native American Tribal Organizations (other than Federally recognized tribal governments)
- Faith-based or Community-based Organizations
- Regional Organizations
- Non-domestic (non-U.S.) Entities (Foreign Institutions)
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.
- Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
- System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
- eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
- Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
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.
NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:
- To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
- Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
- Of an application with a changed grant activity code.
Applicants 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, 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.
The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy
NHBLI applications: Applications proposing new in vivo models for health and disease aimed at overcoming the unique dynamics of heart, lung, and blood systems should include validation studies for the purpose of preclinical experiments that may lead to an Investigational New Drug (IND), Investigational Device Exemption (IDE) or similar regulatory approval.
All applications: If cell lines, reagents or other biomaterials are developed, the applicant must specify how duplicate storage facilities will be maintained so that these materials will not be lost in case of natural disaster. If new strains of animals are developed, the applicant must specify how germ plasm will be cryopreserved and stored in duplicate facilities.
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:
- All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
- GWAS Sharing Plan is not applicable for this FOA.
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.
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 deadline to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications via 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.
Applicants are responsible for viewing their application before the deadline 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.
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.
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 theSystem for Award Management (SAM). 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 Division of Receipt and Referral (DRR) within the Center for Scientific Review (CSR), NIH. Applications that are incomplete will not be reviewed.
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff 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. NHLBI will not accept applications proposing budgets in excess of $500,000 in any given year.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
Important Update: See
NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Significance
Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Investigator(s)
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Innovation
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Approach
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?
Environment
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Protections for Human Subjects
For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
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.
Renewals
For Renewals, the committee will consider the progress made in the last funding period.
Revisions
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.
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.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the National Center for Advancing Translational Sciences,, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
- May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
- Will receive a written critique.
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 appropriate National Advisory Council or Board. The following will be considered in making funding decisions:
- Scientific and technical merit of the proposed project as determined by scientific peer review.
- Availability of funds.
- Relevance of the proposed project to program priorities.
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to the DUNS, SAM
Registration, and Transparency Act requirements as noted on the Award
Conditions and Information for NIH Grants website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Cooperative Agreement Terms and Conditions of Award
Not Applicable
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.
Grants.gov Customer
Support (Questions regarding Grants.gov registration and submission, downloading
or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov
eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov
Oleg Mirochnitchenko, Ph.D.
Division of Comparative Medicine (DCM)
Office of Research Infrastructure Programs (ORIP)
Division of Program Coordination,
Planning, and Strategic Initiatives (DPCPSI)
Telephone: (301) 435-0744
Fax: (301) 480-3819
Email: oleg.mirochnitchenko@nih.gov
Martha S. Lundberg, Ph.D.
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute
Telephone: (301) 435-0513
Fax: (301) 480-1454
Email: lundberm@nhlbi.nih.gov
Nadya Lumelsky, Ph.D.
Integrative Biology and Infectious Disease Branch
National Institute of Dental and Craniofacial Research
Telephone: (301) 594-7703
Fax: (301) 480-8319
Email: nadyal@nidcr.nih.gov
Kristin M. Abraham, Ph.D.
Division of Diabetes, Endocrinology & Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Phone: (301) 451-8048
Fax: (301) 480-0475
Email: abrahamk@mail.nih.gov
Susan R. Haynes, Ph.D.
Division of Genetics & Developmental Biology
National Institute of General Medical Sciences
Telephone: (301) 594-0943
Fax: (301) 480-2228
Email: hayness@nigms.nih.gov
Ross D. Shonat, Ph.D.
Center for Scientific Review (CSR), National Institutes of Health (NIH)
6701 Rockledge Dr., Bethesda, MD 20892
Ph: 301.435.2786, FAX: 301.480.0287
ross.shonat@nih.gov
Kristin Wegner
National Center for Advancing Translational Sciences (NCATS)
Office of Research Infrastructure Programs (ORIP)
Telephone: 301-435-0848
Email: kristin.wegner@nih.gov
Amy Connolly
Office of Grants Management
National Heart, Lung, and Blood Institute
Telephone: (301) 435-0166
Email: connolla@nhlbi.nih.gov
Dede Rutberg, MBA
Grants Management Branch
National Institute of Dental and Craniofacial Research
Telephone: (301) 594-4798
Fax: (301) 480-3562
Email: rutbergd@mail.nih.gov
Natasha Loveless, MBA
Office of Grants Management
National Institute of Diabetes and Digestive and Kidney
Diseases
Telephone: (301) 594-8853
Email: natasha.loveless@nih.gov
Nicole Fleisher
Office of Grants Management
National Institute of General Medical Sciences
Telephone: (301) 594-3923
Fax: (301) 480-2554
Email: fleishen@nigms.nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.
