EMERGING TECHNOLOGIES FOR THE STUDY OF REPRODUCTIVE NEUROENDOCRINOLOGY

RELEASE DATE:  March 19, 2003

PA NUMBER:  PA-03-079

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 R21 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R21 AIDS and AIDS-Related Applications: May 2, 2006 
EXPIRATION DATE for All R01 Applications: March 15, 2006 unless reissued.

National Institute of Child Health and Human Development (NICHD)
 (http://www.nichd.nih.gov/)
National Institute of Neurological Disorders and Stroke (NINDS)
 (http://www.ninds.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:  93.864 AND 93.853

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanism 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 THE PA

The National Institute of Child Health and Human Development (NICHD) 
and the National Institute of Neurological Disorders and Stroke (NINDS) 
invite applications dealing with nervous system control of 
reproduction.  The purpose of this PA is to stimulate the development 
of new technologies and the application of existing innovative 
technologies to answer questions regarding the neuroendocrine control 
of reproduction that, up to this point, could not be answered due to 
limitations in technology.  Answers to these questions are particularly 
critical for human reproduction given the increased evidence for 
altered neuroendocrine function as an etiological underpinning for 
certain reproductive diseases and disorders.

RESEARCH OBJECTIVES

Background

Dubbed as "the Decade of the Brain," the 1990s saw an explosion of 
innovative technologies to probe neurological function.  Of 
significance was the development of new non-invasive procedures to 
monitor real time neural activity such as functional magnetic resonance 
imaging.  This decade also saw the emergence of nanoscience and 
accompanying nanotechnologies, including the availability of powerful 
imaging techniques with cellular and subcellular resolution.  Coupled 
with the development of profiling strategies for genomes and proteomes, 
and laser capture microdissection procedures, the use of non-invasive 
and invasive procedures offers the opportunity to identify functional 
changes in discrete brain regions and the functionally related genes 
that may be responsible for the changes in neural cell activity.  
Importantly, non-invasive imaging approaches allow monitoring of real-
time brain activity in the human.  As such, this PA expresses the 
interest of NICHD and NINDS to support research in the area of 
reproductive neuroendocrinology using these new, and yet to be 
developed, technologies with particular emphasis on human applications. 

Research Scope

Applications submitted in response to this PA may propose hypothesis- 
driven, discovery-driven or developmental research.  Projects deemed 
responsive to this PA include, but are not limited to:  1) basic, 
applied and clinical research proposals that seek to investigate the 
neuroendocrine control of reproduction using innovative invasive or 
non-invasive approaches, and 2) projects that propose to develop new 
technologies to monitor neuroendocrine activity, particularly non-
invasive approaches that have the potential for use in humans.  

Important areas of neuroendocrine regulation of reproductive function 
of interest to NICHD that may be addressed by these technologies 
include, but are not limited to:

o Non-invasive, high-resolution brain imaging techniques to assess in 
vivo changes in hypothalamic reproductive function;

o Electrophysiological, cell imaging and molecular techniques for the 
in situ assessment of the activity of gonadotropin-releasing hormone 
(GnRH), and of other neurons involved in the control of GnRH neuronal 
function;

o Genomic and proteomic approaches to identify and characterize global 
changes in gene and protein expression that occur in the neuroendocrine 
brain and pituitary gland in relation to key physiological events of 
reproductive function;

o Laser capture microdissection approaches coupled to gene profiling 
technology to define the existence of cell-specific changes in gene 
expression in phenotypically identified cells within the neuroendocrine 
brain and pituitary gland;

o Genomic and genetic approaches to identify novel genes and gene 
networks involved in the neuroendocrine control of reproduction;

o Nanotechnology to identify the sub-cellular mechanisms underlying the 
transsynaptic and glial control of GnRH neuronal function;

o Combination of the above-mentioned approaches coupled with 
morphological techniques to identify key changes in synaptic remodeling 
that may occur in the hypothalamus during reproductive life;

o Identification of molecules involved in neuron-neuron and glia-neuron 
adhesiveness and cell-cell signaling within the neuroendocrine brain 
that are important for control of reproduction.

The NINDS encourages the behavioral neuroendocrinology community to 
highlight the new research directions identified in this PA.  NINDS is 
particularly interested in the application of innovative technologies 
to study neural control of reproductive function in clinical 
populations and animal models of neurological disorders where 
reproductive function is compromised.

MECHANISM OF SUPPORT

This PA will use the NIH Research Project Grant (R01) and 
Exploratory/Developmental Grant (R21) award mechanisms.  As an 
applicant you will be solely responsible for planning, directing, and 
executing the proposed project.

Applications for R21 exploratory/developmental grants should be 
submitted with the intent to:  1) generate pilot data to assess the 
feasibility of a novel avenue of investigation; 2) propose high-risk 
experiments that could lead to a breakthrough discovery; or 3) develop 
new technologies that can be utilized for the study of reproductive 
neuroendocrinology.  R21 applications may not request more than 
$125,000 in direct costs per year for up to two years.  Applicants are 
encouraged to contact program staff for advice about choosing the 
appropriate grant mechanism.  These grants are not renewable.

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 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.   

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:  

Louis V. DePaolo, Ph.D.
Reproductive Sciences Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, 8B01H, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 435-6970
Email:  depaolol@mail.nih.gov 

OR

Emmeline Edwards, Ph.D.
Systems and Cognitive Neuroscience
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 2109
Bethesda, MD  20892
Telephone:  (301) 496-9964
Email:  ee48r@nih.gov

o Direct your questions about financial or grants management matters 
to:  

Mary Ellen Colvin
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, 8A17, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-1304
Fax:  (301) 402-0915
Email:  colvinm@mail.nih.gov 

OR

Aaron Kinchen
Grants Management Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 3271
Bethesda, MD  20892
Telephone:  (301) 496-7386
Email:  ak284o@nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  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) 435-0714, Email:  GrantsInfo@nih.gov. 

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 SUBMISSION OF R21 APPLICATIONS:  The Research 
Plan section of the application for R21 Exploratory/Developmental 
applications may not exceed 15 pages.

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:

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 received by or mailed 
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 Receive a written critique
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 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 

DATA SHARING:  The adequacy of the proposed plan to share data. 
 
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.

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 AMENDMENT 
"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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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