This PA will expire on March 4, 2002 unless reissued.


Release Date:  April 3, 2001

PA NUMBER:  PA-01-076

National Center for Research Resources
National Cancer Institute
National Heart, Lung and Blood Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institute of Child Health and Human Development
National Institute of Diabetes and Digestive and Kidney Diseases
National Institute of Mental Health
National Institute of Neurological Disorders and Stroke
National Institute on Deafness and Other Communication Disorders
National Institute on Drug Abuse



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.  This program announcement 
supersedes PA-99-086 issued earlier by the NCRR.


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 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 2010" at


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

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



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) 


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. 
Reviewers are cautioned that their anonymity may be compromised when they 
directly access an Internet site.


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

Forms are online at:

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

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.  (Applications that request more than $250,000 direct costs in any year 
must follow the traditional PHS 398 application instructions.)  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 all 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 all 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 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 and applications will be reviewed for completeness by the 
Center for Scientific Review (CRS).  Applications will be reviewed for 
scientific and technical merit 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.

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 be 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 animals or the environment, to 
the extent they may be adversely affected by the project proposed in the 


Applications will compete for available funds with all other recommended 
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:

John D. Harding, Ph.D.
Division of Comparative Medicine
National Center for Research Resources
6705 Rockledge Drive, Suite 6050 MSC 7965
Bethesda, MD  20892-7965
Telephone: (301) 435-0744
FAX:  (301) 480-3819

Colette Freeman, Ph.D.
Cancer Cell Biology Branch
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, Room 5030
Bethesda, MD 20892-7396
Telephone:  (301) 496-7028
FAX:  (301) 402-1037

Helena Mishoe, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 10156
Bethesda, MD  20892-7950
Telephone:  (301) 435-0050
FAX:  (301) 480-0868

Bernadette Tyree, Ph.D.
Cartilage and Connective Tissue Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Natcher Building, Room 5A37
Bethesda, MD 20892-6500
Telephone:  (301) 594-5032
FAX:  (301) 480-4543

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) 435-6973
FAX: (301) 496-0962

David G. Badman, Ph.D.
Hematology Program 
National Institute of Diabetes and Digestive and Kidney Diseases
2 Democracy Plaza, Room 621 MSC 5458
6707 Democracy Blvd.
Bethesda, MD  20892-5458
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

Arlene Y. Chiu, Ph.D.
Repair and Plasticity Program
National Institute of Neurological Disorders and Stroke
Neuroscience Center, Room 2206
6001 Executive Boulevard
Bethesda, MD 20892
Telephone:  (301) 496-1447
FAX:  (301) 480-1080

Nancy L. Freeman, Ph.D.
Hearing and Balance/Vestibular Branch
National Institute on Deafness and Other Communication Disorders
Executive Plaza South-400C
6120 Executive Boulevard, MSC 7180
Rockville, MD 20852
Telephone:  (301) 402-3458
FAX:  (301) 402-6251

Jonathan D. Pollock, Ph.D.
Genetics and Molecular Neurobiology Research Branch
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4274
Bethesda, MD 20892
Telephone:  (301) 435-1309
FAX:  (301) 594-6043

Direct inquiries regarding fiscal matters to:

Ms. Irene Grissom
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. Crystal Wolfrey
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, Room 243
Bethesda, MD  20892
Telephone:  (301) 496-8634
FAX:  (301) 496-8601

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 Office
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Natcher Building, Room 5A49F
Bethesda, MD  20892-6500
Telephone: (301) 594-3535
FAX:  (301) 480-5450

Ms. Kathy Hancock
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17M
Bethesda, MD  20892-7510
Telephone:  (301) 496-5482
FAX:  (301) 402-0915

Ms. Aretina Perry-Jones
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases
2 Democracy Plaza, Room 632 MSC 5456
6707 Democracy Blvd.
Bethesda, MD  20892-5456
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

Ms. Rita Sisco
Grants Management Branch, DER
National Institute of Neurological Disorders and Stroke
Neuroscience Center, Room 3290, MSC 9537
6001 Executive Boulevard
Bethesda, MD 20892
Telephone:  (301) 496-7488
FAX:  (301) 402-0219

Ms. Sara Stone
Grants Management Office
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-B, MSC 7180
Bethesda, MD 20892-7180
Telephone:  (301) 402-0909
FAX:  (301) 402-1758

Gary Fleming, J.D., M.A.
Grants Management Branch
Office of Planning and Resource Management
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD 20892-9541
Telephone:  (301) 443-6710
FAX:  (301) 594-6847


This program is described in the Catalog of Federal Domestic Assistance Nos. 
93.306, 93.396, 93.839, 93.846, 93.864, 93.849, 93.242, 93.853, 93.173, 93.279.  
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 

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