National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Funding Opportunity Title
Limited Competition for Continuation of Induced Pluripotent Stem Cell (iPSC) Resources promoting Translational Research Advancements in Neurodegenerative Diseases (U24)
U24 Resource-Related Research Projects – Cooperative Agreements
Funding Opportunity Announcement (FOA) Number
Catalog of Federal Domestic Assistance (CFDA) Number(s)
The National Institute of Neurological Disorders and Stroke (NINDS) invites applications for a limited competition Funding Opportunity Announcement (FOA) utilizing a Cooperative Agreement (U24) to provide continuing support for consortia originally funded through the American Recovery and Reinvestment Act of 2009 (ARRA) to develop well characterized, broadly available induced pluripotent stem cell (iPSC) resources for neurodegenerative diseases. A primary goal of this new initiative is to facilitate the scientific evaluation of iPSC resources for drug discovery purposes and to increase the number of lines, types of mutations, reporter modifications, maintenance and differentiation protocols and cell line characterization that are broadly available to the community as research resources. This Initiative is intended to be a partnership with government, non-government organizations and pharmaceutical companies interested in advancing drug discovery efforts for neurodegenerative diseases.
An essential feature of this initiative is that the protocols, clinical and biological data, as well as the fibroblast and iPSC lines developed through the consortia, will be broadly available to all qualified scientific investigators at time intervals to be determined by the iPSC Resource Steering Committee; estimated to be every 3-4 months. Raw data will be made available more frequently. The period of support for Induced Pluripotent Stem Cell Resources funded under this FOA will be two years.
April 14, 2011
Letter of Intent Due Date
Application Due Date(s)
June 22, 2011
AIDS Application Due Date(s)
Scientific Merit Review
Advisory Council Review
Earliest Start Date(s)
September 30, 2011
June 23, 2011
Due Dates for E.O. 12372
Required Application Instructions
It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, 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 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
In 2006, the generation of induced pluripotent stem cells
(iPSCs) from somatic cells through retroviral-driven expression of four
embryonic transcription factors (c-Myc,Oct4, Sox2 and Klf4)(Takahashi, K. and
Yamanaka, S., Cell 126:663-676, 2006) initiated a revolution in resource
development for both the exploration of the cellular basis of human disease and
for therapeutic discovery. Rapid advances in iPSC reprogramming technology
focused on integration-free methods such as transfection of episomal plasmids,
non-integrating viral vectors, small molecule inhibitors, synthetic RNAs,
miRNAs, and protein-driven iPSC induction can now circumvent concerns associated
with viral integration including oncogene reactivation, and the generation of
insertional mutations. iPSC technology is emerging as an unprecedented
opportunity in biomedical research, disease modeling, drug discovery and
regenerative medicine. However, to harness the full potential of this
technology, issues regarding iPSC resource availability, standardization of
iPSC resource quality, iPSC line variability, neuronal and astroglial
differentiation efficiencies, and reproducibility of cellular phenotypes across
iPSC lines and laboratories, still need to be addressed.
Through the American Recovery and Reinvestment Act of 2009 (ARRA), the Grand Opportunities or GO grants program (RFA-OD-09-004) supported large-scale research projects to accelerate critical breakthroughs, early and applied research on cutting-edge technologies, and new approaches to improve the synergy and interactions among multi- and interdisciplinary research teams. Through this ARRA initiative, NINDS funded three consortia to develop well-characterized broadly available, induced pluripotent stem cell (iPSC) lines for Huntington's Disease and familial forms of Parkinson’s disease, and Amyotrophic Lateral Sclerosis. This consortium approach enabled rapid resource and analytical tool development (Boulting, G.L. et al, Nature Biotechnology 29, 279-286, 2011), and the initial identification of cellular phenotypes associated with late-onset neurodegenerative disease in iSPC-derived neuronal cultures. All fibroblast lines and iPSC lines developed through the ALS, PD and HD consortia will be available through the NINDS repository at Coriell. (http://ccr.coriell.org/Sections/Collections/NINDS/FibroSubcollList.aspx?SsId=10&PgId=681&coll=ND)
In 2010, the National Institute of Neurological Disorders and Stroke held two workshops for iPSC consortia investigators, non-government organizations and industry representatives to discuss the progress of consortia in developing iPSC disease-specific lines and protocols or methodologies for cell-type specific differentiation and lineage analysis. The workshops also provided industry perspectives regarding the challenges that remain for the utilization of patient-derived iPSC lines in the drug development process. The research resource needs identified during the workshops for the use of patient-derived iPSC lines in neurodegenerative disease drug discovery efforts are the foundation for this initiative. (http://www.ninds.nih.gov/funding/areas/neurodegeneration/cluster_workshop_schedule.htm)
The purpose of this limited competition FOA is to continue support of iPSC consortia funded under RFA-OD-09-004 and focused on the accelerated development of iPSC research resources broadly available to the community in support of basic and translational research for neurodegenerative diseases.
Functions of the iPSC Research Resource
The following are essential functions of an iPSC research resource for neurodegenerative diseases:
The following are desired but not essential functions of an iPSC research resource for neurodegenerative diseases:
Core Activities of the iPSC Research Resource
To accomplish the essential functions outlined for the iPSC resarch resource, a core(s) should be described that will provide necessary infrastructure for rapid development and characterization of:
Data and Resource Sharing
The following data and resource sharing issues need to be addressed for iPSC research resources under this FOA in addition to all NIH data and resource sharing policies, consistent with meeting the goals of this FOA:
Under the direction of NINDS, a steering committee will be established to advance the general scientific goals of the consortia, which are directed at the development of high quality, well characterized, broadly available iPSC research resources for Neurodegenerative Diseases in an accelerated timeframe. The research resource consortia funded under this FOA will remain flexible to add to the above activities as specified by the iPSC Research Resource Oversight Board to be appointed by the NINDS. PD/PIs of the research resource consortia will be members of the steering committee.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed
The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards
NINDS intends to fund 1-3 awards, corresponding to a total of $4,500,000, for fiscal year 2011. Future year amounts will depend on annual appropriations.
Application budgets are limited to $1,000,000 direct costs per year.
Award Project Period
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.
Foreign (non-U.S.) components of U.S. Organizations are allowed.
Only the three currently funded ALS, PD and HD consortia under RFA-OD-09-004 are eligible to apply.
Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
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 PHS398 Application Guide.
Only institutions/organizations funded previously in response to RFA-OD-09-004 for development of iPSC research resources are eligible to apply. This is a limited competition FOA.
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 in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.
Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.
It is critical that applicants follow the instructions in the PHS398 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.
Applications must be prepared using the PHS 398 research
grant application forms and instructions for preparing a research grant
application. Submit a signed, typewritten original of the application,
including the checklist, and three signed photocopies in one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
At the time of submission, two additional paper copies of
the application and all copies of the appendix files must be sent to:
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke
Room 3201, MSC 9529
6001 Executive Boulevard
Bethesda, MD 20892-9529 (Rockville, MD 20852 for express/courier service)
Telephone: (301) 496-9223
Fax: (301) 402-0182
All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:
All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:
Resource Sharing Plan
Additional Resource Sharing Plan Requirements:
Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.
Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the PHS398 Application Guide.
Part I. Overview Information contains information about Key Dates.
Information on the process of receipt and determining if
your application is considered “on-time” is described in detail in the PHS398
Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.
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
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Available funding will be based on establishment of a partnership in support of the FOA. If appropriations are available for year 2, second year funding will also be based on accomplishment of milestones defined for year 1.
Applications must be received on or before the due dates in Part I. Overview Information. If an
application is received after that date, it will not be reviewed.
Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NINDS. Applications that are incomplete and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
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
Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the iPSC research resource 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 iPSC research resource 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 iPSC research resource that by its nature is not innovative may be essential to advance a field.
Does the iPSC research resource address an important problem or a critical barrier to progress in the field? If the aims of the iPSC research resource 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? If the milestones of the iPSC research resource are met, how will the resources developed contribute to advancements in basic and translational research for neurodegenerative diseases?
Are the PD/PIs, collaborators, and other researchers well suited to the iPSC research resource? 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?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Will the iPSC research resource provide a well characterized broadly available set of iPSC lines for the research community? Will the iPSC research resources developed impact basic and translational research for neurodegenerative diseases?
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the iPSC research resource? 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
If the iPSC research resource 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?
Are milestones for iPSC line development and characterization clearly defined? Is the proposed approach for the distribution of resources among qualified investigators consistent with achieving the goals of the program?
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 iPSC research resource proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.
Is there evidence of productivity during the RFA-OD-09-004 funding period, in terms of broadly available fibroblast lines and the generation and standardized characterization of iPSC lines?
Are milestones defined for the number of new iPSC lines to be developed and characterized under this FOA? Is the timeline for development of new iPSC lines and approach clearly defined and feasible within the accelerated timeframe of the FOA?
Inclusion of Essential Functions for the iPSC Research Resource
Are the essential functions of the iPSC research resource, as defined in Section 2, Part I of this FOA, clearly addressed? Are the necessary personnel, expertise, and facilities available to address the essential functions of the iPSC research resource in the accelerated timeframe of the FOA?
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 iPSC research resource 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.
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 iPSC research resource 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/priority score.
Applications from Foreign Organizations
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 National Institute of Neurological Disorders and Stroke , in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Review assignments will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Applications will be assigned to the appropriate NIH Institute or Center and will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke (NANDS) Council l. 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
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 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, CCR 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.
The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is
applicable when State and local Governments are eligible to apply), and other
HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The NINDS will appoint an Oversight Board for all consortia funded under this FOA.
Areas of Joint Responsibility include:
In collaboration with the NINDS Project Director, the PIs will be responsible for outreach to researchers and organizations to promote and enhance broad data and resource usage across the neuroscience research community.
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.
A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.
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.
Due to the unique requirements of the NINDS Cooperative Program for iPSC Research Resources, applicants are strongly encouraged to consult with NINDS Program Staff as plans for an application are being developed. This early contact will provide an opportunity to clarify the applicant's understanding of program goals and guidelines, including the scope of projects within the program and the requirement that project objectives be milestone-driven. These discussions also provide important information and guidance on how to develop an appropriate milestone plan, which is subject to peer review under this program.
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
eRA Commons Help Desk(Questions regarding eRA Commons
registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
Margaret Sutherland, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Tijuanna DeCoster, MPA
National Institute of Neurological Disorders and Stroke(NINDS)
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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