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 https://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 https://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 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:
https://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:
https://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
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a
complete copy of the updated Guidelines are available at
https://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
https://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
https://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
https://grants.nih.gov/grants/stem_cells.htm and at
https://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
https://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 https://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.