EXPLORATORY CENTER GRANTS FOR HUMAN EMBRYONIC STEM CELL RESEARCH
 
RELEASE DATE:  October 16, 2002
 
RFA:  GM-03-003  (see re-announcement RFA-GM-05-004)

National Institute of General Medical Sciences (NIGMS) 
 (http://www.nigms.nih.gov)
  
LETTER OF INTENT RECEIPT DATE:  February 13, 2003; standard time limit 
for P20s

APPLICATION RECEIPT DATE:  March 13, 2003
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

The National Institute of General Medical Sciences (NIGMS) invites 
applications for P20 Exploratory Grants that will support multi-
investigator teams to conduct research using human embryonic stem cells 
(HESC). The purpose of this RFA is to encourage and enable basic 
biologists with little or no prior HESC experience to work with HESC 
and establish the utility of HESC as a model system by: 1) supporting 
the development of an institutional infrastructure for research using 
HESC; 2) encouraging research on the growth and maintenance 
requirements of HESC; 3) identifying biochemical and molecular markers 
of HESC; 4) stimulating research that will lead to a better 
understanding of the unique properties of HESC; and 5) supporting pilot 
projects that exploit the advantages of HESC as a model system to 
further the study of fundamental research problems. The source of HESC 
will be limited to federally approved stem cell lines listed on the NIH 
Human Embryonic Stem Cell Registry, which can be found at 
http://escr.nih.gov. 

RESEARCH OBJECTIVES

Background

On August 9, 2001, President Bush announced his decision to allow 
Federal funds to be used for research on existing human embryonic stem 
cell lines. Subsequently, the NIH Human Embryonic Stem Cell Registry 
was created to provide a listing of federally approved Human Embryonic 
Stem Cell Lines http://escr.nih.gov that may be used for such research. 
The availability of HESC for federally funded research affords a unique 
opportunity for investigators to use these cells to address fundamental 
research questions. However, most institutions and investigators have 
little or no prior experience in growing and maintaining HESC and 
remarkably little is known about the molecular and genetic properties 
of HESC that distinguish them from more differentiated cells. 
Therefore, NIGMS hosted a workshop on the Basic Biology of Mammalian 
Stem Cells in order to bring stem cell researchers and basic biologists 
together to 1) better understand the unique properties of embryonic 
stem cells and 2) to consider how embryonic stem cells might be 
exploited as a model system to advance the study of fundamental 
research problems. The report of that workshop can be found at 
http://www.nigms.nih.gov/news/reports/stemcellworkshop.html. 
The workshop report summarizes many fascinating opportunities to use 
HESC to study important biological problems and identifies activities 
that need to be addressed in order to stimulate and facilitate the use 
of HESC as a model system. These activities include: continued 
interdisciplinary collaborations and discussions between stem cell 
researchers and basic biologists; characterization of improved 
conditions for the growth of HESC and their maintenance in a 
pluripotent, undifferentiated state; characterization of molecular 
markers that distinguish HESC from more differentiated cells (including 
adult stem cells); and funding initiatives to encourage, enable and 
train basic biologists to work with HESC and to initiate pilot projects 
using HESC as a model system. As a result, NIGMS is issuing this RFA to 
stimulate HESC research and to address these immediate needs. 

Scope of Research

The objective of this RFA is to encourage and enable basic biologists to 
work with HESC and to initiate pilot projects using HESC as a model 
system to study research problems that are central to the mission of 
NIGMS. NIGMS supports basic research that addresses fundamental 
biological questions. Applicants should visit the NIGMS website at 
http://www.nih.gov/nigms for detailed information on NIGMS areas of 
research interest. NIGMS does not support research that is targeted to 
specific organ systems or diseases. 

Areas of research that are appropriate for support by this RFA include:  
1) studies on improved conditions for the growth of HESC and their 
maintenance in an undifferentiated state 
2) further characterization of the unique molecular properties of HESC 
that distinguish them from other stem cell populations (e.g., adult 
stem cells) and from more differentiated cells 
3) development of reagents that will facilitate the use of HESC as a 
model system
4) comparative studies of HESC and adult stem cells or animal stem 
cells
5) pilot studies on the use of HESC as a model system to address basic 
research problems that may include, but are not limited to:
o  regulation of gene expression and gene expression networks 
o  epigenetic regulation of gene expression, including genomic 
imprinting
o  determinants of differentiation, dedifferentiation and nuclear 
reprogramming 
o  chromosome, chromatin and telomere structure and function
o  regulation of cell proliferation  
o  the basis of cell polarity and asymmetric cell division 
o  signaling pathways required for cell adhesion and cell migration
6) pilot studies on the use of HESC as a primary cell type for drug 
discovery.

NIGMS strongly encourages potential applicants to discuss their ideas 
with NIGMS program staff and to send a letter of intent prior to 
submission to ensure that the application will be responsive to the 
NIGMS mission and the intent of this RFA. 

Exploratory Center Grant Activities

Exploratory Center Grants will be expected to: 1) establish and support 
institutional core facilities that can be used for the growth and 
maintenance of HESC, for the further characterization of HESC 
properties, and for development of reagents and tools that will enhance 
the use of HESC as a model system; 2) propose three pilot research 
projects that test the usefulness of HESC as a model system to address 
basic research problems; 3) provide research and training opportunities 
for graduate students and postdoctoral fellows interested in working 
with HESC; and 4) sponsor interdisciplinary workshops or meetings that 
foster an exchange of ideas and information between stem cell 
biologists and basic biologists. NIGMS expects to bring Exploratory 
Center Grant awardees to the NIH at least once during the term of the 
awards to discuss progress and exchange information. Travel funds 
should be budgeted for this purpose.  

MECHANISM OF SUPPORT
 
This RFA will use the NIH P20 Exploratory Center Grant mechanism. 
Applicants will be solely responsible for planning, directing, and 
executing the proposed project. This RFA is a one-time solicitation 
with an expected award date in September, 2003. 

Although P20 Exploratory Grants will not be renewable, NIGMS expects to 
issue a subsequent RFA to support full-scale research centers, using 
the P50 mechanism. Such centers would have expanded core capabilities 
to grow and characterize HESC, to develop tools and reagents needed for 
HESC research, and to manage and disseminate experimental data. Such 
centers would be expected to support multiple research projects 
utilizing HESC to address important biological problems and to offer 
research training and community outreach activities. While award of a 
P20 Exploratory Grant may enhance an institution's subsequent ability 
to apply for a P50 Center Grant for HESC research, receipt of a P20 
Exploratory Center award will not be a pre-requisite for submission of 
future P50 Center applications. 

This RFA uses just-in-time concepts and the non-modular budgeting 
format (see http://grants.nih.gov/grants/funding/modular/modular.htm).  

FUNDS AVAILABLE 
 
NIGMS intends to commit $2 million in FY 2003 to fund two to three new 
P20 Exploratory Grants in response to this RFA. An applicant may 
request a project period of three years and up to $500,000 direct costs 
per year. Costs for major items of equipment or indirect costs 
associated with consortium or sub-contractual arrangements will not be 
considered as part of the $500,000 direct cost limit. Because the 
nature and scope of the proposed research will vary from application to 
application, the size of each award also may vary. Although the 
financial plan of NIGMS sets aside funds to support this initiative, 
awards pursuant to this RFA are contingent upon the availability of 
funds and the receipt of a sufficient number of meritorious 
applications. Exploratory Center Grants will not be renewable. 

ELIGIBLE INSTITUTIONS
 
You may submit an application(s) if your institution is a domestic 
organization and has any of the following characteristics: 

o  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  

Applications from foreign institutions and for-profit organizations 
will not be accepted; however, subcontracts to foreign institutions and 
for-profit organizations may be included.
 
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. Investigators are 
not required to have prior experience with HESC. Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs.   

SPECIAL REQUIREMENTS  

The Principal Investigator of the Exploratory Center Grant will be 
expected to commit a minimum effort of 25%. Applications may be 
considered for Federal funding only if the cell line(s) proposed for 
use is listed on the NIH Human Embryonic Stem Cell Registry 
(http://escr.nih.gov). Applications must specify the HESC cell line to 
be used and include the NIH identification number in the Description on 
page 2. Awards will not be made until access to eligible HESC is 
documented.

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA 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:

o Direct your questions about scientific/research issues to:

Marion Zatz, Ph.D.
Division of Genetics and Developmental Biology
NIGMS
Building 45, Room 2AS-25E
Bethesda, MD  20892-6200
Telephone: (301) 594-0943
Email: zatzm@nigms.nih.gov

o Direct your questions about peer review issues to:

Helen R. Sunshine, Ph.D.
Office of Scientific Review 
NIGMS
Building 45, Room 3AN.12F 
Bethesda, MD  20892-6200
Telephone: (301) 594-2881
Email: sunshinh@nigms.nih.gov

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

Marcia Cohn
Grants Management
NIGMS
Building 45, Room 2AN.44E
Bethesda, MD  20892
Telephone: (301) 594-3918
Email: cohnm@nigms.nih.gov
 
LETTER OF INTENT

Prospective applicants are strongly urged to submit a letter of intent 
that includes the following information:

o  Descriptive title of the proposed research
o  Name, address, and telephone number of the Principal Investigator
o  Names of other key personnel 
o  Participating institutions
o  Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows IC staff to ascertain responsiveness to the RFA 
and IC mission as well as to estimate the potential review workload and 
plan the review.
 
The letter of intent should be sent by the date listed at the beginning 
of this document to:

Marion Zatz, Ph.D.
Division of Genetics and Developmental Biology
NIGMS
Building 45, Room 2AS.25E
Bethesda, MD  20892
Telephone: (301) 594-0943
Email: zatzm@nigms.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.

The page limit for the narrative section (sections a-d) is 40 pages.  
This includes: (1) the overall description; (2) the research plan for 
the pilot projects and (3) the core(s). Please note that there is no 
requirement to submit this maximum number of pages; concise, articulate 
applications are desired.
 
SUPPLEMENTAL INSTRUCTIONS: The identity of the stem cell lines to be 
used must be indicated in the Description on page 2 using official NIH 
identifier codes from the NIH Human embryonic stem cell registry 
http://escr.nih.gov. 

The P20 Exploratory Center Grant application should specify the 
administrative and organizational structure(s) that will be used to 
support the research, including: arrangements, where needed, to acquire 
expertise in growing and maintaining HESC; mechanisms to insure that 
participating investigators meet on a regular basis to exchange 
information; a description of plans for a scientific workshop; and 
opportunities to involve students and fellows in HESC research. 
 
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application. Type the RFA number on the label. Failure to use 
this label could result in delayed processing of the application such 
that it may not reach the review committee in time for review.  In 
addition, the RFA title and number must be typed on line 2 of the face 
page of the application form and the YES box must be marked. The RFA 
label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the Checklist, and three signed 
photocopies, in one package to:
 
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application 
must be sent to:

Helen R. Sunshine, Ph.D. 
Office of Scientific Review 
NIGMS
45 Center Drive, Room 3AN.12F
Bethesda, MD 20892-6200
 
APPLICATION PROCESSING: Applications must be received by the 
application receipt date listed in the heading of this RFA. If an 
application is received after that date, it will be returned to the 
applicant without review.
 
The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA 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 substantial revisions of applications already 
reviewed, but such applications must include an Introduction addressing 
the previous critique.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIGMS. Note that applicants are required to 
include the NIH code number identifying the eligible cell line that is 
to be used in the proposed research. Applications that do not provide 
this information will be returned without review.

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the NIGMS in accordance with the review 
criteria stated below. As part of the initial merit review, all 
applications will:

o  Receive a written critique
o  Undergo a process in which all applications will be discussed and  
assigned a priority score
o  Receive a second level review by the National Advisory General 
Medical Sciences Council. 
 
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 an 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 an application's overall score, weighting them as 
appropriate for each application. 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 
applicant may propose to carry out important work that by its nature is 
not innovative but is essential to move a field forward. If the P20 
Exploratory Center Grant application includes distinct subprojects, the 
scientific merit of each will be assessed, based on its merit as an 
independent effort and its potential importance/contribution to the 
success of the overall effort (however, the projects will not receive 
separate scores).

(1) SIGNIFICANCE:  Do the PI and other investigators address an 
important problem? If the aims of the pilot research projects are 
achieved, how do they advance scientific knowledge? What will be the 
effect of these studies on the concepts or methods that drive this 
field?

(2) APPROACH:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the 
aims of the projects? Do the investigators acknowledge potential 
problem areas and consider alternative tactics?

(3) INNOVATION:  Do the projects employ novel concepts, approaches or 
methods? Are the aims original and innovative? Do the projects 
challenge existing paradigms or develop new methodologies or 
technologies?

(4) INVESTIGATORS:  Has the PI demonstrated the necessary experience, 
judgment and expertise to lead and manage the Center? Are the 
investigators appropriately trained and well suited to carry out this 
work?  Is the work proposed appropriate to their experience level?

(5) ENVIRONMENT:  Does the scientific environment in which the work 
will be done contribute to the probability of success? Do the proposed 
core and pilot projects 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, your 
application will also be reviewed with respect to the following:

o PROTECTIONS:  The adequacy of the proposed protection for humans, 
animals, or the environment, to the extent they may be adversely 
affected by the project proposed in the application.

o INCLUSION:  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. Plans for the 
recruitment and retention of subjects will also be evaluated (see 
Inclusion Criteria included in the section on Federal Citations, 
below).

o BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

OTHER REVIEW CRITERIA:

o Do the proposed plans for the core appear adequate to grow, maintain 
and further characterize HESC?

o Are the choices of pilot projects good ones to exploit the unique 
potential of HESC as a model system?

o If the investigators do not have prior experience or preliminary data 
using HESC, is their overall expertise consistent with proposed core 
activities and pilot studies using HESC? Have they adequately described 
plans to acquire additional expertise?

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  February 13, 2003
Application Receipt Date:  March 13, 2003
Peer Review Date:  June/July, 2003
Council Review:  September, 2003
Earliest Anticipated Start Date:  September, 2003

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
 
REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research 
components involving Phase I and II clinical trials must include 
provisions for assessment of patient eligibility and status, rigorous 
data management, quality assurance, and auditing procedures.  In 
addition, it is NIH policy that all clinical trials require data and 
safety monitoring, with the method and degree of monitoring being 
commensurate with the risks (NIH Policy for Data Safety and Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

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 are 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.

HUMAN EMBRYONIC STEM CELLS (HESC): Criteria for federal funding of 
research on HESCs can be found at 
http://grants.nih.gov/grants/stem_cells.htm 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 (see 
http://escr.nih.gov). It is the responsibility of the applicant to 
provide 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 RFA 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 RFA 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 No. 93.821; 93.862; 93.859 and is not 
subject to the intergovernmental review requirements of Executive Order 
12372 or Health Systems Agency review.  Awards are made under 
authorization of Sections 301 and 405 of the Public Health Service Act 
as amended (42 USC 241 and 284) and administered under NIH grants 
policies described at http://grants.nih.gov/grants/policy/policy.htm 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 

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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