SMALL GRANT PROGRAM FOR THE NIAMS

Release Date:  January 16, 1998

RFA:  AR-98-002

P.T.

National Institute of Arthritis and Musculoskeletal and Skin
Diseases

Application Receipt Date:  April 29, 1998

PURPOSE

The National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) is seeking small grant (R03) applications to
stimulate and facilitate the entry of promising new investigators
into targeted, high priority areas of NIAMS research.  This
one-time solicitation will provide support for pilot research that
is likely to lead to a subsequent individual research project grant
(R01).

HEALTHY PEOPLE 2000

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 Request for Applications (RFA), Small Grant Program
for the NIAMS, is related to the priority area of chronic diseases. 
Potential applicants may obtain a copy of "Healthy People  2000"
(Full Report:  Stock No. 017-001-11474-0 or Summary Report:  Stock
No. 017-001-11473-1) through the  Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone
202-512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by 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.  Foreign
organizations and institutions are not eligible.  Participation in
the program by investigators at minority institutions is strongly
encouraged.  Pilot project grants awarded through this RFA may not
be used to support thesis or dissertation research.

Former and current recipients of NIH small research grants (R03),
Academic Research Enhancement Awards (AREA) (R15), Mentored
Clinical Scientist Development Awards (K08), Mentored Research
Scientist Development Awards (K01), Shannon Awards (R55), or
Individual (F32) or Institutional (T32) National Research Service
Award (NRSA) training support are eligible to apply for this Small
Grant Program, dependent upon the status of other support for the
project. Any current support by the F32 or T32 mechanisms must
terminate before Small Grant support begins. The work proposed may
not overlap significantly with the aims of currently supported
projects in which the Principal Investigator has participated
during the last five years.  (Information on such projects is to be
provided as part of the Principal Investigator's Biographical
Sketch, as described below under Application Procedures.)

Current and previous recipients of NIH funding through Research
Project Grants (R01) or FIRST (R29) awards are ineligible for this
Small Grants Program.  Principal Investigators of research
subprojects of Research Program Projects (P01) and Centers (P50 and
P60) and individuals who have received research support from the
National Science Foundation (NSF) or Department of Veterans Affairs
(VA) as Principal Investigators are also ineligible.  Individuals
whose sole previous support has been through pilot and feasibility
studies may apply.

Investigators who have questions about eligibility should contact
one of the program officials listed under INQUIRIES.

MECHANISM OF SUPPORT

Applicants may request up to $50,000 (direct costs) per year for up
to three years through the small grant (R03) mechanism.  It is
anticipated that grants would be awarded no later than September
30, 1998.  These awards are not renewable.  Before completion of
the R03, investigators are encouraged to seek continuing support
for research through a research project grant (R01).

Replacement of the Principal Investigator on this award is not
permitted.

FUNDS AVAILABLE

It is estimated that $1.0 million (total costs) will be available
to support approximately 10 to 15 awards under this program. 
Awards are contingent on the availability of appropriated funds and
on the receipt of sufficiently meritorious applications meeting the
stated eligibility requirements.

RESEARCH OBJECTIVES

The Small Grant program is designed to facilitate the entry of
promising new investigators into high priority areas identified by
the NIAMS.  Investigators may apply for a small grant to support
research in one of the following general areas:

Angiogenesis

o  Endothelial cell dysfunction leading to changes in adhesiveness
or blood vessel tone; endothelial cell interactions with
inflammatory cells and components of the extracellular matrix;
phenotypic changes and biochemical mechanisms of endothelial cell
response to inflammatory/immune-mediated tissue injury as they
relate to the normal function and diseases of connective tissue.

o  Regulatory factors controlling vascular structure, including
molecular events that regulate angiogenesis, endothelial and
vascular smooth muscle cell growth and cell death in the context of
rheumatic and other connective tissue diseases.

o  Immune responses directed against vascular components

o  Pathogenesis of vascular manifestations of rheumatic and
systemic autoimmune diseases such as lupus, dermatomyositis,
scleroderma and rheumatoid arthritis

o  Studies of vasculitis and vasculopathies in animal models of
rheumatic diseases, with emphasis on identification of pathogenetic
mechanisms and molecular targets for therapeutic intervention

o  Therapeutic potential of angiogenesis inhibitors/modulators in
rheumatoid arthritis

o  Therapeutic potential of angiogenesis inhibitors/modulators in
psoriasis, immune and non-immune inflammation of the skin
(including irritant and allergic contact dermatitis), autoimmune
diseases of skin, atopic dermatitis, and wound healing

o  Inflammatory cell interactions with vasculature in the
initiation of immune and non-immune inflammation of the skin and in
wound healing

o  Mechanisms of exercise-induced changes in vascularization of
muscle, bone, and connective tissue

o  Mechanisms of vascularization of new tissue during wound healing
in skin and muscle.

Mechanisms of self-recognition in autoimmunity

o  Molecular pathways and regulatory steps in self-antigen
processing

o  Physicochemical properties of the complex between
self-components and antigen-presenting molecules

o  Design of therapies to prevent abnormal responses to self by
affecting antigen processing

Stem Cell Biology

o  Identification, isolation, and culture of stem cells of
epidermis and skin appendages, as they relate to skin diseases and
wound healing, and to the development of skin-based gene therapy
for skin and systemic diseases

o  Characterization of the mesenchymal progenitors of chondrocytes
and osteoblasts, including factors that influence commitment to a
particular differentiative pathway, and the ability of the cells to
circulate and/or "home" to specific tissues

o  Characterization of the satellite cells of muscle, including
their derivation, location, relative numbers and relation to other
stem cell types

Growth and Repair of bone and connective tissue, including
cartilage, tendon, ligament and muscle

o Determination and regulation of the osteoblastic and osteoclastic
lineages, including the characterization of precursor cells and key
gene products, interactions with other cells of the marrow
microenvironment, and the role of apoptosis

o Organization and function of the growth plate, including the
differentiation of growth plate chondrocytes and the regulation of
chondrocyte proliferation and hypertrophy

o Mechanisms of bone and connective tissue responses to anabolic
stimuli such as mechanical loading and intermittent PTH

o Interactions of bone and connective tissue with materials of
orthopedic instruments, implants and prostheses, including the
induction of local osteolysis, and the enhancement of integration
with bone

o Response of bone and connective tissue to injury, including
fracture healing, repair of defects resulting from surgery, and
repair of injuries to growth plate, tendon and ligament

o Molecular regulation of chondrogenesis, differentiation or
articular chondrocytes, methodologies of chondrocyte culture,
regulation of cartilage matrix assembly

o Elucidation of biomechanical signal transduction pathways in
chondrocytes, studies on biomechanical regulation of the
structure/function of the cartilage matrix, chondrocyte metabolic
activities, responses to cytokines, gene expression

o Mechanisms of cartilage repair and regeneration, including
chondroprogenitor cell biology, genetics, development of techniques
for chondroprotection and repair of the articular surface,
including gene therapy approaches

Models and Markers of gender and genetic factors in musculoskeletal
injuries and diseases, including animal models of human disease

o Gender differences in risk factors for musculoskeletal injuries

o Analysis of genetic factors in the acquisition and/or loss of
bone mineral density, bone quality, or fracture risk

Other Research

o  Rheumatic and dermatological manifestations of acquired
immunodeficiency syndrome

o  Pathogenesis of alopecia areata and vitiligo.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS

It is the policy of the NIH that women and members of minority
groups and their subpopulations must be included in all NIH
supported  biomedical and behavioral research projects involving
human subjects, unless a clear and compelling rationale and
justification are provided that inclusion is inappropriate with
respect to the health of the subjects or the purpose of the
research.  This new policy results from the NIH Revitalization Act
of 1993 (Section 492B of  Public Law 103-43).

All investigators proposing research involving human subjects
should read the "NIH Guidelines for Inclusion of Women and
Minorities as Subjects in Clinical Research", which have been
published in the Federal Register of March 28, 1994 (FR 59
14508-14513) and in the NIH Guide for Grants and Contracts, Volume
23, Number 11, March 18, 1994.

Investigators also may obtain copies of the policy from the program 
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.

APPLICATION PROCEDURES

Applications are to be submitted on grant application form PHS 398
(rev. 5/95).  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: asknih@od.nih.gov.

The following instructions are to be used in conjunction with the
information accompanying application form PHS 398 (rev. 5/95). 
They refer only to selected items in the application form.  All PHS
398 requirements must be adhered to, with the exception of those
items affected by the following instructions; for example, the
Research Plan is limited to 10 pages.  Applications not conforming
to the requested format will be returned to the applicant without
review. Please note that some of the information to be omitted from
the application at submission may be requested following review if
the possibility of funding exists.

Face Page

o  Item 2,  Response to Specific Program Announcement:  Check the
box marked YES.  Enter the RFA number (AR-98-002) and title (NIAMS
Small Grants Program).

o  Item 6,  Dates of Proposed Period of Support.  Up to a total of
three years of support may be proposed.

o  The RFA label available in the PHS 398 application form must be
affixed to the bottom of the face page of the application.  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.

Detailed Budget for Initial Budget Period (Page 4)

o  Do not complete or submit this page.

Budget for Entire Proposed Period of Support (Page 5)

o  Composite Budget Table:  Enter total direct costs requested, up
to a maximum of $50,000, for each year of support (up to three).

o  Justification:  Provide a narrative justification for each
proposed personnel position, including role on the project and
proposed level of effort

o  Provide narrative justification for the additional resources
requested for the conduct of the project.

Biographical Sketch (Page 6) (Complete for each of the key
personnel listed on Form Page 2.)

o  Research and Professional Experience:  List current position(s)
and those previous positions directly relevant to the application.

o  List selected peer-reviewed publications directly relevant to
the proposed project, with full citations.

o  Provide information on research projects completed and/or
research grants in which the investigator participated during the
last five years which are relevant to the proposed project.  For
each project or grant listed, provide title, name of Principal
Investigator, funding source, and role on project (if not Principal
Investigator).

Other Support (Page 7)

o  Do not complete or submit this section.

Research Plan

o  Items a - d of the Research Plan (Specific Aims, Background and
Significance, Preliminary Studies, and Research Design and Methods)
may not exceed a total of 10 pages.  Please note that a Progress
Report is not needed; no competing continuation applications will
be accepted for an R03.

Appendix

o  Appendix material may not be used to circumvent the page
limitations.  Publications may not be submitted as appendix.

Checklist

o  The Checklist should not be submitted.

Submit a signed original of the application and four signed copies
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, one additional copy of the application
must be sent to:

Tommy L. Broadwater, Ph.D.
Scientific Review Branch
National Institute of Arthritis and Musculoskeletal and Skin
Diseases
45 Center Drive, Room 5AS-25U - MSC 6500
Bethesda, MD  20892-6500

In order not to delay review, it is important that applicants
comply with this request.

Applications must be received by April 29, 1998.  If an application
is received after that date, it will be returned to the applicant
without review.  Only one Small Grant application may be submitted
by a Principal Investigator.  Applicants may not submit an R01 or
any career award (K mechanism) application for the February 1 or
March 1, 1998 receipt date if that application involves significant
scientific overlap with a Small Grant application.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by
CSR.  Incomplete applications will be returned to the applicant
without further consideration.  NIAMS staff will review
applications for responsiveness to the research objectives of this
RFA and for the eligibility of the Principal Investigator under the
requirements stated above.  Applications found to be unresponsive
or ineligible will be returned 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 committee convened by the NIAMS in accordance with the usual
NIH peer review procedures.
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 review, comments on
the following aspects of the application will be made 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 the assignment of the
overall score.

(1) 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 field?

(2) 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?

(3) Innovation

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

(4) 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)?

(5) 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?

In addition, the adequacy of plans to include both genders and
minorities and their subgroups as appropriate for the scientific
goals of the research will be reviewed.  Plans for the recruitment
and retention of subjects will also be evaluated.

The initial review group will also examine the provisions for the
protection of human and animal subjects, the safety of the research
environment, and conformance with the NIH Guidelines for the
Inclusion of Women and Minorities as Subjects in Clinical Research.

AWARD CRITERIA

The following will be considered in making funding decisions:

o  Quality of the proposed project as determined by peer review 
o  Importance of the area to NIAMS research
o  Availability of funds.

INQUIRIES

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

Direct inquiries regarding programmatic issues to one of the
following persons, according to scientific area:

Rheumatic Diseases

Dr. Susana A. Serrate-Sztein
45 Center Drive, Room 5AS-37G
Bethesda, MD  20892-6500
Telephone:  (301) 594-5032
FAX:  (301) 480-4543
Email:  SzteinS@ep.niams.nih.gov

Cartilage and Connective Tissue

Dr. Bernadette Tyree
45 Center Drive, Room 5AS-37J
Bethesda, MD  20892-6500
Telephone: (301) 594-5032
FAX:  (301) 594-4543
Email:  TyreeB@ep.niams.nih.gov

Muscle Biology

Dr. Richard W. Lymn
45 Center Drive, Room 5AS-49E
Bethesda, MD  20892-6500
Telephone:  (301) 594-5128
FAX:  (301) 480-4543
Email:  LymnR@ep.niams.nih.gov

Orthopedics

Dr. James S. Panagis
45 Center Drive, Room 5AS-37K
Bethesda, MD  20892-6500
Telephone:  (301) 594-5055
FAX:  (301) 594-4543
Email:  PanagisJ@ep.niams.nih.gov

Skin Diseases

Dr. Alan N. Moshell
45 Center Drive, Room 5AS-25L
Bethesda, MD  20892-6500
Telephone:  (301) 594-5017
FAX:  (301) 480-4543
Email:  MoshellA@ep.niams.nih.gov

Bone Biology

Dr. William J. Sharrock
45 Center Drive, Room 5AS-37A
Bethesda, MD  20892-6500
Telephone:  (301) 594-5055
FAX:  (301) 480-4543
Email:  SharrocW@ep.niams.nih.gov

Direct inquiries regarding fiscal matters to:

Sally A Nichols
Grants Management Office
National Institute of Arthritis and Musculoskeletal and Skin
Diseases
45 Center Drive, Room 5AS-49F, MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-3535
FAX:  (301) 480-5450
Email:  NicholsS@ep.niams.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.846.  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 PHS grants policies and Federal Regulations 42 CFR 52 and 45
CFR Part 74.  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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