Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Funding Opportunity Title	Model Systems for Fragile X Pre-Mutation and Primary Ovarian Insufficiency (FX-POI) (R21)
Activity Code	R21 Exploratory/Developmental Research Grant Award
Announcement Type	New
Related Notices	None
Funding Opportunity Announcement (FOA) Number	PAR -11-137
Companion FOA	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.865
FOA Purpose	The purpose of this funding opportunity announcement (FOA) is to stimulate the development of new model systems and/or the thorough characterization of the ovarian phenotype of existing models of fragile X associated premature ovarian insufficiency (FX-POI). New and well-characterized models of FX-POI will help us to answer fundamental questions about the role of the FMR1 repeat expansion in ovarian function and reproductive aging, and allow the field to advance into evidence based clinical research on fragile X pre-mutation carriers who are at risk for POI. This research should provide a solid basis for future studies on the mechanism of ovarian dysfunction in women who carry the pre-mutation, facilitating counseling about risks for early infertility and advice about reproductive options.

Posted Date	March 9, 2011
Open Date (Earliest Submission Date)	May 1, 2011
Letter of Intent Due Date	May 1, 2011, May 1, 2012
Application Due Date(s)	June 1, 2011, June 1, 2012, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not applicable
Scientific Merit Review	October/November 2011, October/November 2012
Advisory Council Review	January 2012, January 2013
Earliest Start Date(s)	April 1, 2012, April 1, 2013
Expiration Date	June 2, 2012
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (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

Expansion of the CGG triplet repeat in the promoter region of the "Fragile X Mental Retardation 1" gene, or FMR1, causes a variety of phenotypes depending on the length of the expansion. In the full mutation range of 200 copies or more, FMR1 expansion causes fragile X syndrome (FXS), the most common inherited intellectual and developmental disability. Smaller expansions in the range of approximately 55-200 repeats are termed pre-mutations because although they do not cause intellectual disability, the expansions are unstable and prone to lengthen into full mutations when transmitted through the maternal germ line, causing FXS in the next generation. These pre-mutations of FMR1 can cause other disease phenotypes in adult carriers, including a neurological pathology termed fragile X-associated tremor/ataxia syndrome (FX-TAS), and early onset of menopause, termed fragile X-associated primary ovarian insufficiency (FX-POI, also known as premature ovarian failure or POF).

Primary ovarian insufficiency begins with unusually early hormonal changes such as elevated levels of FSH despite normal menstrual cycles and culminates in menopause before the age of 40. While POI occurs in less than 1 percent of the normal female population, up to 24 percent of fragile X pre-mutation carriers are afflicted. As a group, women who carry the fragile X pre-mutation undergo menopause about 5 years earlier than their peers. The effects of the pre-mutation reach beyond reproductive implications to affect all female carriers because in addition to the early loss of fertility, these women face the potential early onset of serious conditions associated with menopause, including a heightened risk of osteoporosis and cardiovascular disease.

Although we know that the fragile X pre-mutation increases the risk of POI, it is not clear exactly how the mutation disrupts ovarian function and causes the phenotype of early menopause. Understanding the effects of the FMR1 pre-mutation on ovarian function and ovarian aging is critical to help women who carry the fragile X pre-mutation, and it might also lead to insights into other causes of early menopause and female infertility.

In the normal range of less than about 40-50 CGG repeats, the FMR1 gene is transcribed into the protein FMRP, an RNA binding protein that ultimately regulates neuronal connections. Expansion of the CGG triplet repeat to the full mutation size of 200 copies or more silences FMR1 expression through chromatin changes- primarily promoter methylation- that inhibit transcription. FMR1 silencing leads to a deficiency of FMRP that alters the formation of brain circuitry to cause intellectual and developmental disabilities. In contrast, pre-mutation carriers produce abnormally high levels of FMR1 transcripts with the large CGG repeat, but despite the elevated levels of mRNA, their FMRP levels are slightly lower than normal. Studies suggest that the FX-TAS phenotype results not from the decrease of protein, but from toxic effects of the high levels of FMR1 transcripts on neurons. It is unclear how the pre-mutation causes the ovarian phenotype, or even if the effects initiate at the ovary, or result from primary defects in the neurons of the pituitary and/or hypothalamus. The mechanism underlying ovarian dysfunction remains unclear and this hampers progress towards important goals of counseling fragile X pre-mutation carriers about their prognosis, fertility potential, and options for fertility preservation.

Although several lines of genetically engineered mice and flies with FMR1 repeat expansions exist, they are not widely distributed in the scientific community or well-characterized with respect to ovarian function. In addition, in these models the modified FMR1 gene is not specific to the ovary but affects other tissues as well, complicating determination of the role of the ovary vs. the brain or other tissues in the development of POI. The development of new model systems in which expanded FMR1 CGG repeats provoke ovarian insufficiency was promoted as a high priority objective in the "NIH Research Plan on Fragile X Syndrome and Associated Disorders."

The purpose of this FOA is to advance our understanding of the role of the fragile X pre-mutation in the development of primary ovarian insufficiency by developing new animal, tissue or cell culture models of FX-POI, and/or thoroughly characterizing existing models to fully describe the ovarian phenotype, function and pathology arising from the FMR1 repeat expansion, as well as to make these research resources broadly available and accessible to the scientific community for furthering research. In addition to elucidating the role of FMR1 in primary ovarian insufficiency, well-defined, specific and well-characterized model systems will advance our general understanding of ovarian function and ovarian aging, as well as our knowledge of basic pathways underlying other causes of POI. With this information the field can advance to evidence-based clinical research that will inform the care and counseling of young women who carry the fragile X pre-mutation and women with FX-POI.

Applicants may propose to create a new model system for the study of FX-POI and/or characterize the ovarian function and reproductive pathology in an existing model system with an FMR1 CGG repeat expansion in the pre-mutation range.

Investigators proposing to characterize existing models of FX-POI should thoroughly describe the ovarian phenotype and function, as well as hypothalamic-pituitary-ovarian axis function if the model allows, with reference to potential underlying causal mechanisms for POI. Possible variables to consider include but are not limited to: production, secretion and action of hormones made by the ovary; production, secretion and action of hormones that affect ovarian development or function; ovarian histology, follicle numbers, proportions of types of follicles, follicle maturation and loss, and oocyte quality; measures of ovarian cyclicity and fertility; FMR1 chromatin changes and FMR1 mRNA and FMRP expression profiles in the ovary, hypothalamus and pituitary; the effects of FMR1 mRNA or FMRP on ovarian gene expression; the role, if any, of FMR1 in ovarian development; and changes in any of these parameters with reproductive aging. If not previously characterized, the stability of the pre-mutation upon transmission as well as the degree of cellular mosaicism in CGG repeat length and its possible correlation to the severity of the ovarian phenotype could be described. In addition to a thorough characterization of ovarian function, experiments to begin to address the mechanism underlying ovarian changes are strongly encouraged but not required.

Investigators proposing to develop a new model system to study FX-POI should justify the planned model in terms of its utility, advantages relative to existing models, and relevance to human ovarian physiology. Well-justified plans to develop new vertebrate, invertebrate, tissue or cell culture models to study the role of the fragile X pre-mutation in ovarian function are all acceptable under this FOA. Applications to develop a new model system should include a resource sharing plan that will allow broad and rapid dissemination of the model to other scientists. At a minimum, in addition to creating the model system, applicants must verify the proper insertion of the expanded allele, characterize the expression of FMR1 mRNA and FMRP, and determine the stability of the mutation upon transmission. Appropriate models could include but are not limited to: animals with ovary-specific FMR1 pre-mutation knock-in alleles, models using a cross-over design of ovarian transplantation between FMR1 pre-mutation knock-in animals and wild type animals, the creation of a primate model for FX-POI, or systems using cultured follicles or ovarian cells. The development of new invertebrate models would be considered appropriate to this FOA if their creation is well-justified in terms of potential contributions to understanding the role of FMR1 pre-mutation in human ovarian function.

Funding Instrument	Grant
Application Types Allowed	New Resubmission The OER Glossary and the SF 424 (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	The combined budget for direct costs for the two year project period may not exceed $275,000. No more than $200,000 may be requested in any single year.
Award Project Period	The total project period for an application submitted in response to this funding opportunity may not exceed two 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:

• 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

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 Organizations)

Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) 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.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• Grants.gov
• eRA Commons

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 Project 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 SF 424 (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 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. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

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.

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:

Descriptive title of proposed research
Name, address, and telephone number of the PD(s)/PI(s)
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

The letter of intent should be sent to:

Susan Taymans, Ph.D.
6100 Executive Blvd., Rm. 8B01, Rockville MD 20892-7510; for FedEx use Rockville MD 20852
Telephone: 301-496-6517
Email: TaymansS@mail.nih.gov

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 application submission. 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:

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 modifications:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. All applicants are expected to submit a data sharing plan and rapid dissemination of research their findings to the scientific community is strongly encouraged, consistent with achieving the goals of this program. For those proposing to create new animal models, a model organism sharing plan is also expected. Investigators are strongly encouraged to place newly created animal models in established publically available repositories; if not, the PD/PI must describe how they will freely share the model broadly with other scientists, consistent with achieving the goals of this program.

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-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of 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 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 SF 424 (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/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(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 the Central Contractor Registration (CCR). 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, NIH. Applications that are incomplete 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 review system.

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. In this case, thorough characterization of ovarian function in existing models of FX-POI is considered to be of significant impact. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation in the creation of new animal models or the potential impact of proposed studies to characterize ovarian function in existing models, the utility of the newly generated or thoroughly characterized existing model, and the potential for the proposed work to significantly advance our knowledge or understanding of the role of the fragile X pre-mutation in FX-POI. "High risk" approaches to creating new models are acceptable if balanced by a potentially "high payoff" to the use of the model system. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.

Reviewers will provide an overall impact/priority 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? If the project proposes to develop a new model, how useful will that model be and does it have advantages over existing models? If the project proposes to characterize and existing model, will the planned studies provide a comprehensive view of the effects of the pre-mutation on ovarian function?

Investigator(s)

Are the PD/PIs, 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/priority 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

Not applicable.

Revisions

Not applicable

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/priority 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). Is a data sharing plan included, and will it broadly disseminate research findings in a timely and efficient way consistent with achieving program goals? For applications proposing to create new animal models, will the model organism sharing plan allow other investigators broad access to the new animal models in a timely and efficient way consistent with achieving program goals?

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 (assignments will be shown in the eRA Commons), in accordance with NIH peer review policy and procedures, using the stated review criteria.

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/priority 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 National Advisory Child Health and Human Development Councill. 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 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.

Cooperative Agreement Terms and Conditions of Award

Not applicable

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.

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 Commons Help Desk(Questions regarding 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

Susan Taymans, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-6517
Email: taymanss@mail.nih.gov

Dianne Hardy, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1154
Email: dianne.hardy@nih.gov

Mr. Ted Williams
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6996
Email: williate@mail.nih.gov

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

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