Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Cancer Institute (NCI), (http://www.nci.nih.gov/)
National Institute of Environmental Health Sciences (NIEHS), (http://www.niehs.nih.gov/)
Office of Dietary Supplements (ODS), (http://dietary-supplements.info.nih.gov/)

Title: In Utero Exposure to Bioactive Food Components and Mammary Cancer Risk

Announcement Type
New

Update: The following update relating to this announcement has been issued:

Program Announcement (PA) Number: PA-05-059

Catalog of Federal Domestic Assistance Number(s)
93.393, 93.396 , 93.113

Key Dates
Release Date: March 1, 2005
Letters of Intent Receipt Dates: Not applicable
Application Receipt Dates: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details
Peer Review Dates: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details
Council Review Dates: Standard dates apply, please see http://grants.nih.gov/grants.funding/submissionschedule.htm for details
Earliest Anticipated Start Dates: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details
Expiration Date for R21 Non-AIDS Applications: March 2, 2006
Expiration Date for R21 AIDS and AIDS-Related Applications: May 2, 2006
Expiration Date for R01 Non-AIDS Applications: November 2, 2006
Expiration Date for R01 AIDS and AIDS-Related Applications: January 3, 2007

Due Dates for E.O. 12372
Not applicable

Additional Overview Content

Executive Summary

The purpose of this initiative is to invite innovative preclinical R01 and R21 applications that promote research that will enhance the understanding of the relationship between exposures to bioactive food components and/or environmental chemicals in utero , hormonal and growth factor response, gene expression or epigenetic changes and subsequent mammary cancer risk in preclinical models. Although much evidence suggests that dietary components are linked to cancer prevention, the specific nutrients, sites of action, and role of exposure in utero remain elusive. Similarly there are data suggesting a role for environmental agents such as mycotoxins, heterocyclic amines, and environmental chemicals with endocrine activity in the etiology of mammary cancer but the doses, windows of susceptibility and mechanisms are unclear. This funding opportunity encourages applications that apply new high-throughput genomic, epigenomic, proteomic, and metabolomic technologies to determine how dietary exposures in utero influence adult breast cancer susceptibility. The resulting information will help define effective maternal dietary intervention strategies for breast cancer prevention in her offspring.

This funding opportunity will use the NIH investigator-initiated research project grants (R01) and Exploratory/Developmental (R21) award mechanisms. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the numbers, qualities, durations, and costs of the applications received. Application materials and instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. You may submit (an) application(s) if your institution has any of the following characteristics:

There is no limit on the number of scientifically different applications that may be submitted.

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution 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 programs. There is no limitation on the number of different applications an institution or individual may submit. Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

  Section I. Funding Opportunity Description
    1. Research Objectives

  Section II. Award Information
    1. Mechanism(s) of Support
    2. Funds Available

  Section III. Eligibility Information
    1. Eligible Applicants
      A. Eligible Institutions
      B. Eligible Individuals
    2.Cost Sharing or Matching
    3. Other - Special Eligibility Criteria

  Section IV. Application and Submission Information
    1. Address to Request Application Information
    2. Content and Form of Application Submission
    3. Submission Dates and Times
      A. Receipt and Review and Anticipated Start Dates
        1. Letter of Intent
      B. Sending an Application to the NIH
      C. Application Processing
    4. Intergovernmental Review
    5. Funding Restrictions
    6. Other Submission Requirements

  Section V. Application Review Information
    1. Criteria
    2. Review and Selection Process
      A. Additional Review Criteria
      B. Additional Review Considerations
      C. Sharing Research Data
      D. Sharing Research Resources
    3. Anticipated Announcement and Award Dates

  Section VI. Award Administration Information
    1. Award Notices
    2. Administrative and National Policy Requirements
      A. Cooperative Agreement Terms and Conditions of Award
        1. Principal Investigator Rights and Responsibilities
        2. NIH Responsibilities
        3. Collaborative Responsibilities
        4. Arbitration Process
    3. Reporting

  Section VII. Agency Contact(s)
    1. Scientific/Research Contact(s)
    2. Peer Review Contact(s)
    3. Financial/ Grants Management Contact(s)

  Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description

1. Research Objectives

In utero is a vulnerable period

In utero exposures are important determinants of some cancers occurring in children and young adults. For example, exposure to ionizing radiation in utero promotes childhood leukemia and maternal use of diethylstilbestrol during pregnancy has been linked to clear-cell adenocarcinoma of the vagina in their daughters. In addition, maternal diets, specifically the consumption of vegetables, fruits and protein, are linked to decreased risk of childhood leukemia.

The prenatal period is critical in the development of the mammary gland. During this time, the mammary gland is in a largely undifferentiated state, making it particularly vulnerable to a host of environmental forces. Inappropriate nutritional status or exposure to environmental chemicals and the accompanied alteration in growth and endocrine homeostasis may permanently change the fetus' structure, physiology, and metabolism thereby predisposing it to various diseases in later life including mammary cancer.

In utero exposures and human breast cancer risk

Epidemiological studies suggest that altering the intrauterine nutritional status can increase mammary cancer risk. Failure of the materno-placental supply line to satisfy fetal nutrient requirements can result in a range of fetal adaptations and developmental changes. Birth weight is a gross surrogate marker for shifts in a host of metabolic processes. Many, but not all, studies reveal a positive relationship between increased birth weight and breast cancer risk. Likewise, other indicators of fetal size such as increased placental weight and birth length are positively correlated with breast cancer risk in the offspring. Recent studies suggest that birth weight is independent from neonatal growth patterns and the timing of puberty as a risk factor for breast cancer.

In addition to nutrition, the hormonal environment in the womb may play an important role in programming lifelong risk for breast cancer in the female offspring. A reduction in circulating levels of estrogens and insulin like growth factor-1 (IGF-1), and/or elevated levels of progesterone, androgens, human chorionic gonadotrophin, IGF-1 binding proteins 1 and 3, cortisol and insulin have been associated with reduced risk. Such hormonal and growth factor changes are observed during preeclampsia. Maternal preeclampsia has been associated with a reduction in the female offspring's later risk for breast cancer after adjustment for a variety of potential confounders.

Mammary gland development, dietary modification and mammary cancer risk

Proliferation of primitive ductal structures in the newborn breast leads to branching and terminal end buds (TEBs). The expansion of TEBs represents an opportunity for malignant transformation because they contain pluripotent mammary stem cells. In fact, in utero exposures that bring about an increase in TEBs coincide with increased mammary carcinogenesis. Evidence exists that providing maternal diets that contain elevated amounts of n-6 polyunsaturated fatty acids (PUFAs) and genistein not only increased TEBs but also reduced the differentiation of TEBs to lobuloalveolar units. These diets also increased subsequent chemically induced mammary cancer in the offspring. In addition, prenatal exposures to environmental agents, such as bisphenol A or dioxin, results in alteration in the development of the mammary gland that may predispose to the development of cancers later in life. Some of this response may relate to changes in hormonal and growth factor status including estrogen and IGF-1.

Estrogen, dietary modification and mammary cancer risk

Greater estrogen exposure throughout a woman's life has been identified as a major risk factor for the development of breast cancer. In utero exposures to the mammary gland can achieve concentrations 10-100 times the estrogen levels occurring later in life. Dietary factors, such as genistein and fat, that influence estrogen exposure to the fetus are related to subsequent cancer risk in several model systems. However, the response may not be totally explained by estradiol, since n-3 fatty acid rich diets fed to pregnant rats, elevate this hormone but reduce mammary cancer incidence in the offspring.

It is possible that intrauterine exposure to other hormones or environmental hormone mimics or antagonists may also affect breast cancer susceptibility. Androgen exposure in utero may confer long-term protection against breast cancer by antagonizing the effects of estrogens on fetal breast ductal development. Dietary fatty acids, phytoestrogens, alcohol and lycopene are among the various bioactive food components reported to influence androgen concentrations. Environmental agents with estrogenic agonist or antagonist activity may also alter gene expression during development that may lead to functional deficits later in life that predispose to cancer development. Thus there is the need for future studies focusing on uncovering the mechanisms responsible for the protective and detrimental effects of exposure to bioactive food components and other environmental agents in utero on breast cancer risk. These studies should attempt to address more comprehensively the changes in all potentially relevant pregnancy hormones and growth factors.

IGF, dietary modification and breast cancer risk

The IGF-1 system may play a crucial role in the increased risk that heavier newborns have of developing breast cancer later in life. Birth weight is positively associated with increased insulin and IGF-1 concentrations. Analysis of mammary gland development in knockout mice made deficient in IGF-I or in the IGF-I receptor demonstrates the importance of the IGF system for normal mammary gland development because these mice have diminished TEB development. Observational and preclinical studies provided added evidence that one or more components of the IGF-1 system may be intimately linked to the process of carcinogenesis in the mammary gland. Transgenic mice that overexpress IGF-I or -II display specific alterations in mammary gland development such as an inhibition of mammary cell apoptosis following weaning and an increased incidence of mammary tumors. Thus, increased exposure to IGF-1 in utero may serve as a marker for the relationship between fetal growth and adult cancer susceptibility.

Although the effects of in utero exposure to dietary components have been inadequately examined, considerable evidence exists for their ability to modify IGF-1 concentrations and mammary cancer susceptibility postnatally. Postnatal caloric restriction decreases IGF-1 and decreases mammary tumor growth and metastases. Furthermore, postnatal soy phytochemicals combined with green tea synergistically inhibited mammary tumor growth and depressed serum IGF-1 levels in mice. Future studies are warranted to determine whether in utero exposure to dietary manipulations that modulate IGF-1 expression will influence subsequent breast cancer risk.

Epigenetics, dietary modification and breast cancer risk

Maternal nutritional status can also alter the epigenetic state of the fetal genome and imprint gene expression levels with lifelong consequences. Loss of imprinting is the silencing of active imprinted genes or the activation of silent imprinted genes, and is one of the most common epigenetic changes associated with the development of a wide variety of tumors. For example, loss of imprinting of IGF-2 has been associated with many different types of cancer including mammary tumor development. H19, a tumor suppressor gene located directly downstream from IGF-2, is also genomically imprinted, and is associated with various cancers. Furthermore, the hereditary disorder Beckwith-Wiedemann syndrome, which predisposes to cancer and causes prenatal overgrowth, involves alterations in IGF-2 and H19 imprinting. Several lines of evidence support the relationship between maternal nutrition and epigenetic changes in their offspring. First, a deficiency of amino acids results in marked reduction in genomic DNA methylation and aberrant expression of the normally silent paternal H19 allele in cultured mouse embryos. Second, uteroplacental insufficenty causes hypomethylation and increased histone acetylation in postnatal rat liver. Third, maternal supplementation of methyl donors and cofactors (folic acid, vitamin B-12, choline and betaine) increases CpG methylation at the Avy locus of agouti mouse pups which causes a shift from a yellow to an agouti coat. The methylation patterns are retained into adulthood and are linked with a lower risk of cancer, diabetes, obesity and prolonged life. Thus, epigenetic changes may provide a molecular mechanism for the impact of maternal nutrition or environmental chemical exposures on postnatal disease susceptibility and deserves future research.

Objectives and scope

Investigators may choose from the full range of preclinical approaches. The use of genetically engineered animal models including transgenic or knockouts, such as those available through the mouse models of human cancer consortium (MMHCC, http://emice.nci.nih.gov/), are encouraged. Studies that apply new high-throughput genomic, epigenomic, proteomic, and metabolomic technologies to determine how dietary and/or environmental chemical exposures in utero influence adult breast cancer susceptibility are encouraged.

Illustrative examples for the development of R01 or R21 applications include, but are not limited to, the following examples:

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanisms of Support

This funding opportunity will use the NIH investigator-initiated research project grants (R01) and Exploratory/Developmental (R21) award mechanism(s). As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses just-in-time concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format described in the PHS 398 application instructions. Otherwise follow the instructions for non-modular research grant applications.

2. Funds Available

No set –aside funds are available for this funding opportunity. Applicants may request up to five years of support for R01 awards with costs appropriately tailored to the proposed work. No limit is set on the costs requested by R01 applicants. An R21 applicant may request a project period of up to 2-years with a combined budget for direct costs of up $275,000 for the 2-year period. For example, the applicant may request $100,000 in the first year and $175,000 in the second year. The request should be tailored to the needs of the project. Normally, no more than $200,000 may be requested in any single year. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the ICs provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-05-004.html.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution 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 programs.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing.

3. Other-Special Eligibility Criteria
Not applicable

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

For specific instructions on preparing R21 applications, see the link at http://grants.nih.gov/grants/funding/r21.htm.

3. Submission Dates and Times
Applications must be mailed on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates

Letter of Intent Receipt Date: not applicable
Application Receipt Dates: http://grants.nih.gov/grants/funding/submissionschedule.htm
Peer Review Dates: http://grants.nih.gov/grants/funding/submissionschedule.htm
Council Review Dates: http://grants.nih.gov/grants/funding/submissionschedule.htm
Earliest Anticipated Start Dates: http://grants.nih.gov/grants/funding/submissionschedule.htm

3.A.1. Letter of Intent
A letter of intent is not required for the funding opportunity.

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. Submit a signed, typewritten original of the application, including the checklist, and five 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)

3.C. Application Processing

Applications must be submitted on or before the application receipt dates described above (Section IV.3.A.) and at http://grants.nih.gov/grants/dates.htm. Upon receipt, applications will be evaluated for completeness by CSR.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such application must include an Introduction addressing the previous critique.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

4. Intergovernmental Review
This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm (see also Section VI.3. Reporting).

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

Specific Instructions for Modular Grant applications.

Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget format. The modular budget format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 at http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step guidance for preparing modular budgets. Applicants must use the currently approved version of the PHS 398. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm.

Specific Instructions for Applications Requesting $500,000 (direct costs) or More per Year.

Applicants requesting $500,000 or more in direct costs for any year must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the application, i.e., as you are developing plans for the study;

2) Obtain agreement from the IC staff that the IC will accept your application for consideration for award; and,

3) Include a cover letter with the application that identifies the staff member and IC who agreed to accept assignment of the application.

This policy applies to all investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended or revised version of these grant application types. Additional information on this policy is available in the NIH Guide for Grants and Contracts, October 19, 2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a plan for sharing research data in their application. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).

The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

1. Criteria
Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications submitted for this funding opportunity will be assigned to the ICs on the basis of established PHS referral guidelines.

Appropriate scientific review groups convened in accordance with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific and technical merit.

As part of the initial merit review, all applications will:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

2. Approach. Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

3. Innovation. Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

4. Investigators. Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates
Not applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

A formal notification in the form of a Notice of Grant Award (NGA) will be provided to the applicant organization. The NGA signed by the grants management officer is the authorizing document.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

The NGA will be sent via either e-mail or via regular mail to the administrative official whose name is listed in Block 12 on the Face Page of the Form PHS 398.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the notice of grant award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award
Not applicable

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

National Cancer Institute (NCI)
Cindy D. Davis, Ph.D.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, EPN Room 3159, MSC 7328
Bethesda, MD 20892-7328
Rockville, MD 20852 (express/courier service)
Telephone: (301) 594-9692
FAX: (301) 480-3925
Email: davisci@mail.nih.gov

Office of Dietary Supplements (ODS)
Mary Frances Picciano, Ph.D., R.D.
Office of Dietary Supplements
6100 Executive Boulevard, Room 3B01
Bethesda, MD 20892-7517
Rockville, MD 20852 (express/courier service)
Telephone: 301-435-3608
Email: PiccianM@mail.nih.gov

National Institute of Environmental Health Sciences (NIEHS)
Jerry Heindel, Ph.D.
Cellular, Organs and Systems Pathobiology Branch
Division of Extramural Research and Training
POB 12233 RTP, NC, 27709
79.T.W. Alexander Drive, 4401 bldg (express/courier service)
Telephone: 919-541-0781
FAX: 919-541-5064
Email: heindelj@niehs.nih.gov

2. Peer Review Contacts:
Not applicable

3. Financial or Grants Management Contacts:

Ms. Connie Murphy
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard
Executive Plaza South, Room 243
Bethesda, MD 20892
Rockville, MD 20852 (express/courier service)
Phone: (301) 496-8657
FAX: (301) 496-8601
Email: murphco@gab.nci.nih.gov

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review.

Public Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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