Release Date:  April 13, 1999

PA NUMBER: PA-99-086


National Center for Research Resources
National Heart, Lung and Blood Institute
National Institute of Child Health and Human Development
National Institute of Diabetes and Digestive and Kidney Diseases
National Institute of Mental Health

Application Receipt Dates:  June 1, 1999; October 1, 1999; February 1, 2000



The purpose of this program announcement (PA) is to encourage the submission of
applications for research to enhance stem cells as a model biological system. 
Research to isolate, characterize and identify totipotent and multipotent stem
cells from nonhuman biomedical research animal models, as well as to generate
reagents and techniques to characterize and separate those stem cells from other
cell types is encouraged.  Innovative approaches to the problems of making
multipotent stem cells available from a variety of nonhuman sources, and to
creating reagents that will identify those stem cells across species and allow
for separation  of multipotent stem cells from differentiated cell types, will
be stressed.  Accordingly, the Exploratory/Developmental Grants (R21) and
Research Project (R01) grant mechanisms will be used.


The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This PA, Novel Approaches to Enhance Stem
Cell Research, is related to the priority areas of cancer, heart disease and
stroke, diabetes and chronic disability conditions, maternal and infant health,
and others.  Potential applicants may obtain a copy of "Healthy People 2000"
(Full Report:  Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary
Report:  Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800).


Applications may be submitted by foreign and domestic, for-profit and non-profit
organizations, public and private, such as universities, colleges, hospitals,
laboratories, units of State and local governments, and eligible agencies of the
Federal government.  Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as principal investigators.


The Exploratory/Developmental Grants (R21) mechanism and the Research Project
(R01) grant mechanism will be used to support projects under this Program
Announcement (PA).  Under these mechanisms, the applicant will plan, direct and
carry out the research program.  The proposed project period during which the
research will be conducted should adequately reflect the time required to
accomplish the stated goals and be consistent with the policy for grant support. 
However, because the purpose of R21 grants is to help applicants acquire
preliminary data for use in preparing traditional Research Project grant (R01)
or Resource-Related Research Project grant (R24) applications, support for the
R21 grants is limited to two years with a maximum of $100,000 direct costs
requested per year.

For R01 grant applications, applicants planning to submit an investigator-
initiated new (type 1), competing continuation (type 2), competing supplement,
or any amended/revised version requesting $500,000 or more in direct costs for
any year are advised that they must contact the Institute or Center (IC) program
staff before submitting the application, i.e., as plans for the study are being
developed.  Furthermore, the applicant must obtain agreement from the IC staff
that the IC will accept the application for consideration for award.  Finally,
the applicant must identify, in a cover letter sent with the application, the
staff member and Institute or Center who agreed to accept assignment of the
application.  This policy requires an applicant to obtain agreement for
acceptance of both any such application and any such subsequent amendment. Refer
to the NIH Guide for Grants and Contracts, March 20, 1998 at

Either R21 applications or R01 applications requesting $250,000 or less in direct
costs should conform to modular grant application procedures as outlined below
and in the section of this announcement entitled Application Procedures.

For applications requesting $250,000 or less in direct costs, specific
application instructions have been modified to reflect "MODULAR GRANT" and "JUST-
IN-TIME" streamlining efforts being examined by the NIH.  The modular grant
concept establishes specific modules in which direct costs may be requested as
well as a maximum level for requested budgets.  Only limited budgetary
information is required under this approach.  The just-in-time concept allows
applicants to submit certain information only when there is a possibility for an
award.  It is anticipated that these changes will reduce the administrative
burden for the applicants, reviewers and Institute staff.  Complete and detailed
instructions and information on Modular Grants can be found at

The following information in this section refers only to applications using the
modular grant procedures.

o  Applications requesting $250,000 or less in direct costs, must request direct
costs in $25,000 modules, up to a total direct cost request of $250,000 per year. 
A typical modular grant application will request the same number of modules in
each year.

o  Application budgets will be simplified.  Detailed categorical budget
information will not be submitted with the application; budget form pages of the
application kits will not be used.  Instead, total direct costs requested for
each year will be presented.  Information, in narrative form, will be provided
only for Personnel and, when applicable, for Consortium/Contractual Costs.  See
the section on application instructions below.

o  Additional narrative budget justification will be required in the application
only if there is a variation in the number of modules requested.

o  There will be no routine escalation for future years.  In determining the
total for each budget year, applicants should first consider the direct cost of
the entire project period.  Well-justified modular increments or decrements in
the total direct costs for any year of the project that reflect substantial
changes in expected future activities may be requested.  For example, purchase
of major equipment in the first year may justify a higher overall budget in the
first, but not in succeeding years.

o  Other Support pages of the PHS 398 will not be submitted with the application.

o  Information on research projects ongoing or completed during the last three
years of the principal investigator and key personnel will be provided as part
of the "Biographical Sketch."  This information will include the specific aims,
overall goals and responsibilities and should include Federal and non-Federal
support. This information will be used by reviewers in the assessment of each
individual's qualifications for a specific role in the proposed project.

o  Following peer review, information about Other Research Support will be
requested by NIH from the applicant for applications being considered for award.

o  Additional budget information will be requested only under special



Embryonic stem cells, and other stem cells are valuable biomedical research
models for the study of biological and disease processes, and for creation of
disease models.  In addition, these cells hold tremendous promise as model
systems for development of therapeutics and for development of replacement
tissues through understanding of control of their differentiation.

Thus far, embryonic stem cells have been isolated from several biomedically
important nonhuman research models.  In addition, stem cells with a more
restricted potential have been characterized from post-embryonic tissue types. 
However, research is needed to provide for a full array of totipotent and
multipotent  stem cells from nonhuman biomedical research animal models, as well
as to provide the research tools to identify, characterize, and purify those

This initiative will support the isolation and characterization of embryonic and
other multipotent stem cells in a variety of nonhuman animal species.  Examples
of research areas appropriate to this announcement include, but are not limited

o  Projects to expand the number of nonhuman animal model systems in which
embryonic stem cells are available

o  Projects to identify, isolate, culture and characterize multipotent stem cell
populations derived from nonhuman embryonic stem cells

o  Projects to identify, isolate, culture and characterize multipotent stem cells
from post-fetal tissue types

o  Projects to generate and use panels of markers for stem cell attributes common
across species for use in characterization and isolation of stem cells in a range
of animal species or tissues

o  Projects to create universal methods of culture to maintain the
undifferentiated state of embryonic or other characterized, multipotential stem
cells across nonhuman animal species.

Projects supported by the National Center for Research Resources under this PA
are intended to generate research tools, reagents or multipotential stem cells
of utility to research on a broad range of tissue or cell types and of interest
to more than one categorical or disease-oriented Institute or Center of the
National Institutes of Health.  Projects that will focus on research on tissues
or disease processes specific to the mission of an Institute or Center should be
directed to the respective Institute or Center.

The research supported under this PA should clearly expand the usefulness of
nonhuman animal model systems by generating multipotential stem cells appropriate
to those systems and tools that will allow for further research on those stem
cells.  The results of R21 projects are expected to include preliminary data
appropriate for applications for further support through the Research Project
grant (R01) or Resource-Related Research Projects grant (R24) mechanism.


Applications are to be submitted on the grant application form PHS 398 (rev.
4/98) and will be accepted at the standard application deadlines as indicated in
the application kit.  Application kits are available at most institutional
offices of sponsored research and may be obtained from the Division of Extramural
Outreach and Information Resources, National Institutes of Health, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301-710-0267, email:  Forms are online at

The title and number of the announcement must be typed in Section 2a on the face
page of all applications.

Applications requesting $250,000 or less in direct costs per year should conform
to modular grant application procedures as announced in the NIH Guide, December
15, 1998.  Instructions for the PHS 398 form should be followed except, for
applications under modular grant procedures, the following special instructions

o  FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in
$25,000 increments up to a maximum of $250,000) and Total Costs [Modular Total
Direct plus Facilities and Administrative (F&A) costs] for the initial budget
period.  Items 8a and 8b should be completed indicating the Direct and Total
Costs for the entire proposed period of support.

of the PHS 398.  It is not required and will not be accepted with the

categorical budget table on Form Page 5 of the PHS 398.  It is not required and
will not be accepted with the application.

o  NARRATIVE BUDGET JUSTIFICATION - Use a Modular Grant Budget Narrative page.
(See for sample pages.) 
At the top of the page, enter the total direct costs requested for each year.

o  Under Personnel, List key project personnel, including their names, percent
of effort, and roles on the project. No individual salary information should be

o  For Consortium/Contractual costs, provide an estimate of total costs (direct
plus facilities and administrative) for each year, each rounded to the nearest
$1,000.  List the individuals/organizations with whom consortium or contractual
arrangements have been made, the percent effort of key personnel, and the role
on the project.  Indicate whether the collaborating institution is foreign or
domestic.  The total cost for a consortium/ contractual arrangement is included
in the overall requested modular direct cost amount.

o  Provide an additional narrative budget justification for any variation in the
number of modules requested.

o  BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by
reviewers in the assessment of each individual's qualifications for a specific
role in the proposed project, as well as to evaluate the overall qualifications
of the research team.  A biographical sketch is required for all key personnel,
following the instructions below. No more than three pages may be used for each
person.  A sample biographical sketch may be viewed at:

-Complete the educational block at the top of the form page;
-List current position(s) and then previous positions;
-List selected peer-reviewed publications, with full citations;
-Provide information, including overall goals and responsibilities, on research
projects ongoing or completed during the last three years.

o  CHECKLIST - This page should be completed and submitted with the application. 
If the F&A rate agreement has been established, indicate the type of agreement
and the date. It is important to identify all exclusions that were used in the
calculation of the F&A costs for the initial budget period and all future budget

 For all applications, the completed original application and five legible copies
must be sent or delivered to:

CENTER FOR SCIENTIFIC REVIEW (formerly Division of Research Grants)
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)


Applications will be assigned on the basis of established Public Health Service
referral guidelines.  Applications will be reviewed for scientific and technical
merit by study sections of the Center for Scientific Review, NIH (or by the
review group of the relevant Institute, Center, or Division), in accordance with
the standard NIH peer review procedures.  As part of the initial merit review,
all applications will receive a written critique and may undergo a process in
which only those applications deemed to have the highest scientific merit,
generally the top one half of applications under review, will be discussed,
assigned a priority score, and receive a second level review by the appropriate
national advisory council or board.

Review Criteria

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  In the
written comments reviewers will be asked to discuss the following aspects of the
application in order to judge the likelihood that the proposed research will have
a substantial impact on the pursuit of these goals.  Each of these criteria will
be addressed and considered in assigning the overall score, weighting them as
appropriate for each application.  Note that the application does not need to be
strong in all categories to be judged likely to have major scientific impact and
thus deserve a high priority score.  For example, an investigator may propose to
carry out important work that by its nature is not innovative but is essential
to move a field forward.

o  Significance:  Does this study address an important problem?  If the aims of
the application are achieved, how will scientific knowledge by advanced?  What
will be the effect of these studies on the concepts or methods that drive this

o  Approach:  Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project?  Does the applicant acknowledge potential problem areas and consider
alternative tactics?

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

o  Investigator:  Is the investigator appropriately trained and well suited to
carry out this work?  Is the work proposed appropriate to the experience level
of the principal investigator and other researchers (if any)?

o  Environment:  Does the scientific environment in which the work will be done
contribute to the probability of success?  Do the proposed experiments take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements?  Is there evidence of institutional support?

Innovation and potential significance of the proposed research are major
considerations in the evaluation of applications for R21 grants.

In addition to the above criteria, in accordance with NIH policy, all
applications will be reviewed with respect to the following:

o  Appropriateness of the proposed budget and duration in relation to the
proposed research

o  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.


Applications will compete for available funds with all other approved
applications assigned to that Institute or Center.  The following will be
considered in making funding decisions:
o  Quality of the proposed project as determined by peer review
o  Availability of funds
o  Program priority.


Inquiries are encouraged.  The opportunity to clarify any issues or questions
from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Jill L. Carrington, Ph.D.
Comparative Medicine
National Center for Research Resources
6705 Rockledge Drive, Room 6164
Bethesda, MD  20892
Telephone: (301) 435-0744
FAX:  (301) 480-3659

Carol H. Letendre, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, MSC 7950
Bethesda, MD  20892-7950
Telephone:  (301) 435-0080
FAX:  (301) 480-0867

Richard J. Tasca, Ph.D.
Center for Population Research
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room B01-MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-6515
FAX: (301) 496-0962

David G. Badman, Ph.D.
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS-13C, MSC 6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-7717
FAX:  (301) 480-3510

Hemin R. Chin, Ph.D.
Division of Basic and Clinical Neuroscience Research
National Institute of Mental Health
6001 Executive Boulevard, Room 7190, MSC 9643
Bethesda, MD  20892-9643
Telephone:  (301) 443-1706
FAX:  (301) 443-9890

Direct inquiries regarding fiscal matters to:

Ms. Joellen Harper
Office of Grants Management
National Center for Research Resources
6705 Rockledge Drive, Room 6086
Bethesda, MD  20892
Telephone:  (301) 435-0844
FAX:  (301) 480-3777

Ms. Jane R. Davis
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, MSC 7926
Bethesda, MD  20892-7926
Telephone: (301) 435-0166
FAX:  (301) 480-3310

Ms. Melinda Nelson
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B17-MSC7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-5481
FAX:  (301) 402-0915

Ms. Aretina Perry
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AN-38B, MSC 6600
Bethesda, MD  20892
Telephone:  (301) 594-8862
FAX:  (301) 480-3504

Ms. Diana S. Trunnell
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD  20892-9605
Telephone: (301) 443-2805
FAX:  (301) 443-6885


This program is described in the Catalog of Federal Domestic Assistance Nos.
93.849, 93.839, 93.864, 93.848, 93.242.  Awards are made under authorization of
the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended
by Public Law 99-158, 42 USC 241 and 285) and administered under NIH grants
policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74 or 92.  This
program is not subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a smoke-
free workplace and promote the non-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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