EXPLORATORY CENTER GRANTS FOR HUMAN EMBRYONIC STEM CELL RESEARCH   
 
RELEASE DATE:  March 5, 2004
 
RFA Number:  RFA-GM-05-004  

EXPIRATION DATE: October 20, 2004

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 General Medical Sciences (NIGMS) 
 (http://www.nigms.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.859

LETTER OF INTENT RECEIPT DATE:  September 20, 2004
APPLICATION RECEIPT DATE:  October 19, 2004  

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 Supplementary Instructions
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 Center grants that will support multi-
investigator teams to conduct pilot research using human embryonic stem 
cells (HESC).  This is a re-announcement of RFA-GM-03-003 
(http://grants.nih.gov/grants/guide/rfa-files/RFA-GM-03-003.html). 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 Human Embryonic Stem 
Cell Registry, which can be found at http://escr.nih.gov. 

RESEARCH OBJECTIVES

Background

On August 9, 2001, President Bush announced that Federal funds could 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 lines 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 biochemical 
and molecular 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 
(http://www.nigms.nih.gov/news/reports/stemcellworkshop.html) 
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 
biomedical scientists; 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 scientists to work 
with HESC and to initiate pilot projects using HESC as a model system. 
This RFA was first announced in FY2003. NIGMS is re-announcing this RFA 
to further stimulate HESC research and to continue to address these 
immediate needs. 

Scope of Research

The objective of this RFA is to encourage and enable basic scientists 
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.nigms.nih.gov/ 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., embryonic 
germ cells, adult stem cells) and from more differentiated cells 
3) development of reagents and tools that will facilitate the use of 
HESC as a model system
4) comparative studies of HESC with other pluripotent stem cells (e.g. 
embryonic germ cells, 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  regulation of programmed cell death  
o  the basis of cell polarity and asymmetric cell division 
o  signaling pathways required for cell adhesion and cell migration
6) the use of HESC as a primary cell type for drug discovery studies. 

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 research on 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 a minimum of 
three pilot 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; and 4) 
sponsor interdisciplinary workshops or meetings that foster an exchange 
of ideas and information between stem cell researchers and basic 
biomedical scientists. NIGMS expects to bring Exploratory Center grant 
awardees to the NIH at least once during the term of these 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 award mechanism.  
As an applicant you will be solely responsible for planning, directing, 
and executing the proposed project.  This RFA is a one-time 
solicitation.  The anticipated award date is August, 2005. 

P20 Exploratory Center grants will not be renewable. However, NIGMS may 
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 basic research projects 
utilizing HESC to address important biological problems and to offer 
research training and community outreach activities. While award of a 
P20 Exploratory Center 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 P50 Center grant applications. 

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

FUNDS AVAILABLE
 
NIGMS intends to commit approximately $2.7 million in FY 2005 to fund 
two to three new P20 Exploratory Center grants in response to this RFA. 
An applicant may request a project period of up to three years and a 
budget for direct costs of up to $600,000 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 $600,000 
direct costs limit. Because the nature and scope of the proposed 
research will vary from application to application, it is anticipated 
that the size of each award also will vary. Although the financial plan 
of NIGMS provides support for this program, awards pursuant to this RFA 
are contingent upon the availability of funds and the receipt of a 
sufficient number of meritorious applications.  
 
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  
o Foreign institutions are not eligible to apply. 
 
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 an Exploratory Center grant will be 
expected to commit a minimum effort of 25%. Applications will 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 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 M. Zatz, Ph.D.
Division of Genetics and Developmental Biology
NIGMS
Building 45, Room 2AS-25E, MSC 6200
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, MSC 6200 
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, MSC 6200
Bethesda, MD  20892-6200
Telephone: (301) 594-3918
Email: cohnm@nigms.nih.gov

LETTER OF INTENT
 
Prospective applicants are asked 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 estimate the potential review 
workload and plan the review.
 
The letter of intent is to be sent by the date listed at the beginning 
of this document.  The letter of intent should be sent to:

Marion M. Zatz, Ph.D.
Division of Genetics and Developmental Biology
NIGMS
Building 45, Room 2AS-25E, MSC 6200
Bethesda, MD  20892-6200
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). 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 document 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.
 
SUPPLEMENTARY INSTRUCTIONS: 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.
 
The identity of the stem cell lines to be used must be indicated in the 
Abstract 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 train 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/labels.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 and 
all copies of the appendix material must be sent to:

Helen R. Sunshine, Ph.D. 
Office of Scientific Review 
NIGMS
45 Center Drive, Room 3AN.12F, MSC 6200
Bethesda, MD 20892-6200
  
APPLICATION PROCESSING: Applications must be received on or before 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. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
funding assignment within 8 weeks.
 
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.  Revisions of applications previously submitted in response 
to RFA-GM-03-003 will be accepted, 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 NIGMS. Incomplete and/or nonresponsive 
applications will not be reviewed. 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 Undergo a process in which all applications will be discussed and 
assigned a priority score
o Receive a written critique
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 evaluate the 
application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals. The 
scientific review group will address and consider each of the following 
criteria in assigning the application’s overall score, weighting them 
as appropriate for each application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The application does not need to be strong in all categories to be 
judged likely to have major scientific impact and thus deserve a good 
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. The scientific merit of each distinct pilot 
subproject of the P20 Exploratory Center grant application 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 subprojects will not receive separate scores.

SIGNIFICANCE: Do the PI and other investigators address important 
problems? If the aims of the pilot projects 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 projects? Do the investigators acknowledge potential problem areas 
and consider alternative tactics?

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

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 the experience level of the 
principal investigator and other researchers? 

ENVIRONMENT: Does the scientific environment in which the work will be 
done contribute to the probability of success? Do the proposed core(s) 
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, the 
following items will be considered in the determination of scientific 
merit and the priority score:

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

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

o Has an effort been made to include investigators with little or no 
prior experience with HESC?

o Is the overall expertise of investigators with little or no prior 
HESC experience or preliminary data consistent with proposed core 
activities and pilot studies using HESC? Have they adequately described 
plans to acquire additional expertise?

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.  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 REVIEW CONSIDERATIONS

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

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  September 20, 2004
Application Receipt Date:  October 19, 2004
Peer Review Date:  February/March 2005
Council Review:  May 2005
Earliest Anticipated Start Date:  August, 2005

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 

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.

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 (see 
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 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. 

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.healthypeople.gov/.

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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