ENDOMETRIAL CELL FUNCTION
RELEASE DATE: February 3, 2004
PA NUMBER: PA-04-056
January 3, 2007 - Effective with the February 5, 2007 submission date,
all R01 applications must be submitted through Grants.gov using
the electronic SF424 (R&R) application. Accordingly, the R01 portion
of this funding opportunity expires on January 3, 2007. Unsolicited
or investigator-initiated R01 electronic SF424 (R&R) applications may
be submitted through the Research Project Grant (Parent R01) announcement.
March 2, 2006 (NOT-OD-06-046) Effective with the June 1, 2006 submission date,
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using
the electronic SF424 (R&R) application. This announcement will stay active for
only the May 1, 2006 AIDS and AIDS-related application submission date for these
mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms
expires on the date indicated below. Other mechanisms relating to this announcement
will continue to be accepted using paper PHS 398 applications until the stated
expiration date below, or transition to electronic application submission. Parent
R03 (PA-06-180) and R21 (PA-06-181) funding opportunity announcements have been
issued for the submission date of June 1, 2006 and submission dates for AIDS and
non-AIDS applications thereafter. Applications relating to R33 and R34 activities
must be in response to NIH Institute/Center (IC)-specific announcements.
EXPIRATION DATE for R03 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R03 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
Department of Health and Human Services (DHHS)
PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
(http://www.nih.gov)
COMPONENT OF PARTICIPATING ORGANIZATION:
National Institute of Child Health and Human Development (NICHD)
(http://www.nichd.nih.gov/)
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.865
THIS PA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this PA
o Research Objectives
o Mechanisms of Support
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS PA
The purpose of this program announcement is to solicit applications for
support of basic pre-clinical research to enhance our understanding of
etiology, and to improve treatment and prevention, of endometriosis. Special
emphasis is placed on studies of cellular and molecular aspects of endometrial
cell functions and their regulatory mechanisms. This PA is intended to
increase our knowledge of: (1) how the sloughed endometrial fragments in
menstrual flow become adhesive, invasive, and proliferate in ectopic sites;
(2) what molecules are involved in adhesion, invasion, and proliferation of
endometrial cells at ectopic sites; and (3) what function of ectopic
endometrial tissues results in pain and other adverse effects including
infertility.
RESEARCH OBJECTIVES
Background
Progress of research on endometriosis is slow. The recent NIH workshop
entitled "Endometriosis: Emerging Research and Intervention Strategies," held
in April 2001, revealed that we have little basic cell biological knowledge of
endometrial cells. In order to understand etiology, and to improve treatment
and prevention of endometriosis, we must have fundamental knowledge of the
functions of endometrial cells and their regulatory mechanisms. NICHD
supports a small number of investigator-initiated research projects on the
basic aspects of endometriosis, despite the fact that a large number of
patients are suffering from this disease. Little is known about how the
endometrial fragments detach from the uterine lining and retrograde into the
abdominal cavity and become adhesive, invasive, and proliferate in the extra-
uterine sites. In order to prevent its occurrence, to treat this disease
properly, it is essential to understand the basic functions of the endometrial
cells in ectopic and eutopic sites. What are the molecules produced by these
cells that are responsible for adhesion and attachment of these cells to the
surfaces of the peritoneal cavity? What are the cellular mechanisms involved
in invasion of the surface epithelium of the abdominal wall and other tissues
by these endometrial cells? How can we prevent attachment of endometrial
cells to the extra-uterine sites? We need additional basic information to
provide answers that will impact the management of this disease.
Research Scope
Investigators submitting applications in response to this PA are encouraged to
address a basic function of endometrial cells pertaining to endometriosis.
Specific research topics responsive to this announcement include, but are not
limited to, the following:
(1) identification and characterization of molecules that facilitate
endometrial fragment attachment to other epithelial surface such as
intercellular adhesion molecules, or coupling by ligand-receptor interactions;
(2) identification of the regulatory mechanisms that facilitate expression of
the genes of these molecules, such as hormones, growth factors, Ca ion, etc.,
and inhibition of the gene expression that may prevent endometriosis;
(3) characterization of the mechanism of invasion by endometrial fragments of
the epithelium to determine whether endometrial fragments invade in a similar
way as cancer metastasis or blastocyst implantation into the endometrium;
(4) characterization of proliferation of endometrial tissue in ectopic sites
to determine if there is similarity to decidualization or if there is any
specific behavior in their cell division;
(5) analysis of ectopic endometrial cell function that results in pain, to
determine if this is this due to production of prostaglandins or any other
factors;
(6) clarification of the effect of endometriotic lesions on fertility. Does
endometriotic tissue produce extra amounts of estrogen that alter the normal
hypothalamic-pituitary-ovarian axis feedback mechanism or does endometriotic
tissue produce any other substance(s) that affect normal function of the
eutopic endometrium?
MECHANISM OF SUPPORT
This PA will use the NIH Research Project Grant (R01) and Small Grant (R03)
award mechanisms. As an applicant you will be solely responsible for planning,
directing, and executing the proposed project.
Applicants for the NIH Small Grant (R03) should follow the guidelines
published in the NIH Guide for Grants and Contracts at:
http://grants.nih.gov/grants/guide/pa-files/PA-03-108.html.
This PA uses just-in-time concepts. It also uses the modular as well as the
non-modular budgeting 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 format. Otherwise follow the instructions for non-
modular research grant applications. This program does not require cost
sharing as defined in the current NIH Grants Policy Statement at
http://grants.nih.gov/grants/policy/nihgps_2001/part_I_1.htm.
ELIGIBLE INSTITUTIONS
You may submit an application if your institution has any of the following
characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to carry
out the proposed research is invited to work with his/her 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.
WHERE TO SEND INQUIRIES
We encourage your inquiries concerning this PA and welcome the opportunity
answer questions from potential applicants. Inquiries may fall into two
areas: scientific/research and financial or grants management issues:
o Direct your questions about scientific/research issues to:
Koji Yoshinaga, Ph.D.
Program Director, Reproductive Endocrinology
Reproductive Sciences Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B01, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 496-6515
FAX: (301) 480-2389
Email: yoshinak@mail.nih.gov
o Direct your questions about financial or grants management matters to:
Kathy Hancock
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, 8A17, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 496-5482
FAX: (301) 402-0915
Email: kh246t@nih.gov
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant application
instructions and forms (rev. 5/2001). Applications must have a Dun and
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the
Universal Identifier when applying for Federal grants or cooperative
agreements. The DUNS number can be obtained by calling (866) 705-5711 or
through the web site at http://www.dunandbradstreet.com/. The DUNS number
should be entered on line 11 of the face page of the PHS 398 form. The PHS 398
is available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an
interactive format. For further assistance contact GrantsInfo, Telephone
(301) 710-0267, Email: GrantsInfo@nih.gov.
The title and number of this program announcement must be typed on line 2 of
the face page of the application form and the YES box must be checked.
APPLICATION RECEIPT DATES: Applications submitted in response to this program
announcement will be accepted at the standard application deadlines, which are
available at http://grants.nih.gov/grants/dates.htm. Application deadlines
are also indicated in the PHS 398 application kit.
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting
up to $250,000 per year in direct costs must be submitted in a modular grant
format. The modular grant 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 (rev. 5/2001) at
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step
guidance for preparing modular grants. Additional information on modular
grants is available at
http://grants.nih.gov/grants/funding/modular/modular.htm.
SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR:
Applications requesting $500,000 or more in direct costs for any year must
include a cover letter identifying the NIH staff member within one of NIH
institutes or centers who has agreed to accept assignment of the application.
Applicants requesting more than $500,000 must carry out the following steps:
1) Contact the IC program staff at least six 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) Identify, in a cover letter sent with the application, 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.
SENDING AN APPLICATION TO THE NIH: 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
Bethesda, MD 20817 (for express/courier service)
APPLICATION PROCESSING: Applications must be mailed on or before the receipt
dates described at
http://grants.nih.gov/grants/funding/submissionschedule.htm.
The CSR will not accept any application in response to this PA that is
essentially the same as one currently pending initial review unless the
applicant withdraws the pending application. The CSR 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 weeks.
PEER REVIEW PROCESS
Applications submitted for this PA will be assigned on the basis of
established PHS referral guidelines. An appropriate scientific review group
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:
o Undergo a selection process in which only those applications deemed to have
the highest scientific merit, generally the top half of applications under
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the appropriate national advisory council
or board.
REVIEW CRITERIA
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments, reviewers will be asked to discuss the following aspects
of the application in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals:
o Significance
o Approach
o Innovation
o Investigator
o Environment
The scientific review group will address and consider each of these criteria
in assigning the application's overall score, weighting them as appropriate
for each application. The 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.
SIGNIFICANCE: Does this study address an important problem? If the aims of
the application are achieved, how will scientific knowledge be advanced? What
will be the effect of these studies on the concepts or methods that drive this
field?
APPROACH: Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics?
INNOVATION: Does the project employ novel concepts, approaches or methods?
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?
INVESTIGATOR: Is the investigator 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 (if any)?
ENVIRONMENT: Does the scientific environment in which the work will be done
contribute to the probability of success? Do the proposed experiments take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements? Is there evidence of institutional support?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following
items will be considered in the determination of scientific merit and the
priority score:
PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human
subjects and protections from research risk relating to their participation in
the proposed research will be assessed. (See criteria included in the section
on Federal Citations, below).
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of
plans to include subjects from both genders, all racial and ethnic groups (and
subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of
subjects will also be evaluated. (See Inclusion Criteria in the sections on
Federal Citations, below.)
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
398 research grant application instructions (rev. 5/2001) will be assessed.
ADDITIONAL CONSIDERATIONS
SHARING RESEARCH DATA: Applicants requesting more than $500,000 in direct
costs in any year of the proposed research are expected to include a data
sharing plan in their application. The reasonableness of the data sharing
plan or the rationale for not sharing research data will be assessed by the
reviewers. However, reviewers will not factor the proposed data sharing plan
into the determination of scientific merit or priority score.
BUDGET: The reasonableness of the proposed budget and the requested period of
support in relation to the proposed research.
AWARD CRITERIA
Applications submitted in response to a PA will compete for available funds
with all other recommended applications. The following will be considered in
making funding decisions:
o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Relevance to program priorities
REQUIRED FEDERAL CITATIONS
HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and
others, and the importance of the knowledge gained or to be gained
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date,
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,
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.
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of
the NIH that women and members of minority groups and their sub-populations
must be included in all NIH-supported clinical research projects unless a
clear and compelling justification is provided indicating that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research. This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).
All investigators proposing clinical research should read the "NIH Guidelines
for Inclusion of Women and Minorities as Subjects in Clinical Research -
Amended, October, 2001," published in the NIH Guide for Grants and Contracts
on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a)
all applications or proposals and/or protocols must provide a description of
plans to conduct analyses, as appropriate, to address differences by
sex/gender and/or racial/ethnic groups, including subgroups if applicable; and
b) investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:
The NIH maintains a policy that children (i.e., individuals under the age of
21) must be included in all human subjects research, conducted or supported by
the NIH, unless there are scientific and ethical reasons not to include them.
This policy applies to all initial (Type 1) applications submitted for receipt
dates after October 1, 1998.
All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines" on the inclusion of children as participants in
research involving human subjects that is available at
http://grants.nih.gov/grants/funding/children/children.htm.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject participants for
all investigators submitting NIH proposals for research involving human
subjects. You will find this policy announcement in the NIH Guide for Grants
and Contracts Announcement, dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
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.
HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of "Healthy
People 2010," a PHS-led national activity for setting priority areas. This PA
is related to one or more of the priority areas. Potential applicants may
obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.
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.
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