and Human Services (HHS)
EXPIRED
STEM CELLS IN DEVELOPMENT/REPAIR OF OROFACIAL STRUCTURES
RELEASE DATE: February 5, 2002
RFA: RFA-DE-02-006
PARTICIPATING INSTITUTES AND CENTERS (ICs):
National Institute of Dental and Craniofacial Research (NIDCR)
(http://www.nidr.nih.gov/)
LETTER OF INTENT RECEIPT DATE: March 18, 2002
APPLICATION RECEIPT DATE: April 18, 2002
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of the RFA
o Research Objectives
o Mechanism(s) 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
The purpose of this RFA is to foster research on embryonic and adult
stem cell biology that could facilitate the understanding of the
complex events that occur during oral, dental, and craniofacial
development. It is envisioned that such knowledge will aid in the
development of safe and effective stem cell-based treatments for the
repair and regeneration of orofacial structures that have been
compromised by congenital disorders, diseases, and injuries.
RESEARCH OBJECTIVES
Brief Background
Recent scientific discoveries concerning the ability of human embryonic
stem cells (ES) to proliferate in an undifferentiated state and to be
directed to develop into a wide array of cell types present
opportunities for research that aim to repair or replace cells and
restore vital functions. Exploration of these opportunities is now
possible with the release of the NIH Guidelines for Human ES Cell
Research and the availability of human cell lines through the NIH Human
ES Cell Registry.
Adult stem cells are present in many tissues of adult organisms and are
important in tissue repair and homeostasis. These cells have the
ability to self-renew (give rise to a replacement cell at each cell
division with no apparent limitation) as well as generate another cell
that is committed to differentiation in a particular tissue.
Understanding the mechanisms of stem cell renewal could provide
fundamental insights not only into the origin of multicellular
organisms, but also into regeneration of specific tissues and
elucidation of complex events such as tumorigenesis, whereby a "cancer
stem cell" with a similar capacity for self-renewal drives disease progression.
ES cells that are derived from embryos at the blastocyst stage may have
a broader natural potential since, during development, they normally
produce all the cells of an organism. These pluripotent cells are
characterized by nearly an unlimited self-renewal and differentiation
capacity which can give rise to many differentiated cell types
including neurons, glia, skeletal myocytes, adipocytes and haemopoietic
cells. The main difference between the embryo-derived pluripotent cells
and the so-called multipotent adult stem cells is in the number of
differentiated cell types that they can produce. This may reflect the
different origins of these cells, pluripotent stem cells are derived
from blastocyst cells, while adult stem cells are derived from somatic
cells that no longer possess the capacity to develop into the full
spectrum of cell types. The stem and precursor cells can be used for
examining mechanisms of progenitor cell differentiation and identifying
environmental signals that are specific for cell maintenance, cell
renewal and activation of differentiation pathways.
Research Objectives and Scope
In order to develop safe and effective stem cell-based treatments, it
is essential to understand the signals or cues that regulate the stem
cell capacity for self-renewal, cell fate determination, and
maintenance of orofacial tissue homeostasis throughout life. Therefore
the objectives of this RFA are to encourage research on:
o the use of human embryonic stem cell lines listed in the NIH Human
Embryonic Stem Cell Registry. These cell lines can be used for
examining mechanisms of progenitor cell differentiation and may also
have characteristics that make them potentially useful for stem cell-
based therapy,
o progenitor cells of the orofacial ectoderm and the cranial neural
crest-derived mesenchyme, whose interaction during embryonic
development gives rise to the craniofacial tissues including teeth,
salivary glands, cartilage, bone, peripheral nerves, oral epithelium
and smooth muscle, and
o adult stem cells in the orofacial and other body tissues (e.g., bone
marrow, fat, blood) that have the ability to give rise to oral, dental,
and craniofacial tissues and organs.
Topic areas of emphasis might include but are not limited to:
o identification and characterization of the stem cell population(s)
in terms of molecular markers and cell lineage in oral, dental and
craniofacial tissues and organs,
o design of conditions for maintenance, ex vivo, of cell populations
that retain their pluripotency or their multipotency,
o use of stem cells to understand the genetic mechanisms that regulate
development of orofacial structures, the maintenance of tissues in
health and the repair or regeneration of tissues following trauma and disease,
o development of markers that distinguish stem and progenitor
populations and gene profiles that characterize all stages of differentiation,
o investigation of the mechanisms that regulate self-renewal of stem
cells in the oral epithelium, salivary gland, tooth structures and
other craniofacial structures (e.g., bone, cartilage, muscles and nerves),
o use of stem cell lines to identify the environmental cues and
conditions that are required for a human embryonic stem cell to give
rise to cells that make up the different tissues of the orofacial complex,
o identification of signals, signaling pathways components, and
transcriptional factors that regulate the fate(s) of transplanted human
stem cells and their derivatives,
o identification, characterization, and reproduction of the
microenvironment ("niches") of stem and progenitor cells,
o identification of the optimal type of stem cell or stem cell
derivative for specific assays and cell therapy for orofacial diseases
and disorders,
o use of animal model systems of oral, dental and craniofacial
diseases and disorders for screening and comparing the functional
capabilities of implanted human stem cells and their progeny.
MECHANISM OF SUPPORT
This RFA will use the Exploratory/Developmental R21 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. Future unsolicited, competing-continuation applications
based on this project will compete with all investigator-initiated
applications and will be reviewed according to the customary peer
review procedures. The anticipated award date is September 30, 2002.
This RFA uses just-in-time concepts. It also uses the modular
budgeting format. (see
http://grants.nih.gov/grants/funding/modular/modular.htm).
FUNDS AVAILABLE
The NIDCR intends to commit approximately $750,000 in FY 2002 to fund 4
to 5 new grants in response to this RFA. An applicant may request a
project period of up to 2 years and a budget for direct costs of up to
$100,000 per year. Although the financial plans of the NIDCR provide
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 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 institutions
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 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:
Direct your questions about scientific/research issues to:
Eleni Kousvelari, DDS, D.Sc.
Biotechnology and Biomaterials Program
Cellular & Molecular Biology, Physiology
& Biotechnology Branch
Division of Basic and Translational Sciences
National Institute of Dental and Craniofacial Research
Building 45 Room 4AN-18A
Bethesda, MD 20892
Telephone: (301) 594-2427
FAX: (301) 480-8318
Email: [email protected]
Yasaman Shirazi, Ph.D.
Epithelial Cell Regulation and Transformation Program
Cellular & Molecular Biology, Physiology
& Biotechnology Branch
Division of Basic and Translational Sciences
National Institute of Dental and Craniofacial Research
Natcher Building, Room 4AN-18C
Bethesda, MD 20892-6402
Telephone: (301) 594-4812
FAX: (301) 480-8318
Email: [email protected]
Rochelle K. Small, Ph.D.
Developmental Biology and Mammalian Genetics Program
Cellular & Molecular Biology, Physiology
& Biotechnology Branch
Division of Basic and Translational Sciences
National Institute of Dental and Craniofacial Research
Natcher Building, Room 4AN-18D
Bethesda, MD 20892
Phone: (301) 594-9898
Fax: (301) 480-8318
Email: [email protected]
Guo H. Zhang, Ph.D.
Physiology, Prarmacogenetics and Injury Program
Cellular & Molecular Biology, Physiology
& Biotechnology Branch
Division of Basic and Translational Sciences
National Institute of Dental and Craniofacial Research
Building 45 Room 4AN-18A
Bethesda, MD 20892-6402
Telephone: (301) 594-0618
FAX: (301) 480-8318Phone:
Email: [email protected]
Direct your questions about peer review issues to:
H. George Hausch, Ph.D.
Acting Director,
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
National Institutes of Health
45 Center Drive, Room 4AN-44F
Bethesda, MD 20892-6402
Telephone: (301) 594-2904
FAX: (301) 480-8303
Email: [email protected]
Direct your questions about financial or grants management matters to:
H. George Hausch, Ph.D.
Acting Director,
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
National Institutes of Health
45 Center Drive, Room 4AN-44F
Bethesda, MD 20892-6402
Telephone: (301) 594-2904
FAX: (301) 480-8303
Email: [email protected]
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 March 18, 2002. The letter of
intent should be sent to:
Eleni Kousvelari, DDS, D.Sc. Chief,
Cellular & Molecular Biology, Physiology
& Biotechnology Branch
Division of Basic and Translational Sciences
National Institute of Dental and Craniofacial Research
Building 45 Room 4AN-18A
Bethesda, MD 20892
Telephone: (301) 594-2427
FAX: (301) 480-8318
Email: [email protected]
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) 710-0267, Email: [email protected].
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.
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:
H. George Hausch, Ph.D.
Acting Director,
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
National Institutes of Health
45 Center Drive, Room 4AN-44F
Bethesda, MD 20892-6402
Telephone: (301) 594-2904
FAX: (301) 480-8303
Email: [email protected]
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 NIDCR. Incomplete and/or non-responsive
applications will be returned to the applicant without further consideration.
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 NIDCR in accordance with the review
criteria stated below. As part of the initial merit review, all
applications will:
o Undergo a process in which only those applications deemed to have
the highest scientific merit, generally the top half of the applications
under review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the NIDCR National Advisory 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 your 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 your application"s overall score, weighting them
as appropriate for each application. Your 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,
you may propose to carry out important work that, by its nature, is not
innovative but is essential to move a field forward.
(1) SIGNIFICANCE: Does your study address an important problem? If the
aims of your application 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 project? Do you acknowledge potential problem areas and
consider alternative tactics?
(3) INNOVATION: Does your project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does your project
challenge existing paradigms or develop new methodologies or technologies?
(4) INVESTIGATOR: Are you appropriately trained and well suited to
carry out this work? Is the work proposed appropriate to your
experience level as the principal investigator and to that of the other
researchers (if any)?
(5) ENVIRONMENT: Does the scientific environment in which your 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, 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.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: March 18, 2002
Application Receipt Date: April 18, 2002
Peer Review Date: June, 2002
Council Review: August, 2002
Earliest Anticipated Start Date: September, 2002
AWARD CRITERIA
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
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. 93.121, Oral Diseases and Disorders
Research Awards, 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.
Weekly TOC for this Announcement
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