Full Text PA-97-100
NIH Guide, Volume 26, Number 29, August 29, 1997
PA NUMBER:  PA-97-100


National Institute of Allergy and Infectious Diseases
National Institute on Aging
National Institute of Diabetes and Digestive Diseases and Kidney
National Institute of Arthritis and Musculoskeletal and Skin Diseases
The National Institute of Allergy and Infectious Diseases (NIAID),
the National Institute on Aging (NIA), the National Institute of
Diabetes and Digestive and Kidney Disease (NIDDK), and the National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS),
National Institutes of Health (NIH), invite applications to enhance
our knowledge of mechanisms that control the immune response, age-
related changes in the regulation of immune responses, and the
underlying mechanisms responsible for these changes.  Enhanced
knowledge in these areas is needed for the generation and control of
immune responses to antigenic challenges and for the development of
new strategies to treat and prevent immunologically based diseases.
Support will be provided for basic and pre-clinical studies using
molecular and cellular approaches to dissect the immune response.
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 Program
Announcement (PA), "REGULATION OF THE IMMUNE RESPONSE", is related to
the priority areas of Immunization and Infectious Diseases and
Diabetes and Chronic Disabling Disease.  Potential applicants may
obtain a copy of "Healthy People 2000" (Full Report:  Stock No.
017-001-00474-0 or 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 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.  Domestic and foreign
institutions are eligible to apply for R01 grants.  Foreign
institutions are not eligible for First Independent Research Support
and Transition (FIRST) awards.  Racial/ethnic minority individuals,
women, and persons with disabilities are encouraged to apply as
Principal Investigators.
Traditional research project grant (R01) and FIRST (R29) applications
may be submitted in response to this PA.  Applications for R01 grants
may request up to five (5) years of support; applications for R29
grants must request five years of support.
Responsibility for the planning, direction, and execution of the
proposed research for all applicable mechanisms of support will be
solely that of the applicant.
Investigation is needed to enhance understanding of the activation of
signaling pathways in immune system cells, the development of
effector cell specificity, phenotype and function, and processes
involved in the overall regulation of immune responses.  For example,
the molecular control of immunoglobulin gene expression and gene
recombination has progressed significantly with the identification of
enhancer elements, switch recombination sequences and immunoglobulin
germline heavy chain transcription from cryptic promoters. The
finding that the same molecular machinery used for immunoglobulin
gene recombination is also used for the T-cell receptor gene
recombination shows economy of the system.  However, it has been
demonstrated that the intracellular and external regulatory signals
that trigger and control the recombination processes in the two
systems are different.
While many components of immune cell regulation have been discovered,
including pathways of antigen processing and subsequent Major
Histocompatibility Complex (MHC) association as well as the
activities of cytokines, chemokines and growth factors, the
complexity of the emerging picture suggests that many regulatory
processes are still unknown.  One example is how signals from the
surface of immune cells are differentially interpreted to lead to
either stimulation or suppression of immune function.  Little is
known about how the immune system is influenced by and interacts with
other systems, including the endocrine and nervous systems.  It is
expected that continued support of immunological research will ensure
further progress leading to a better understanding of the immune
Research Objectives and Scope
The major objective of this PA is to continue support for research to
elucidate the molecular machinery and control of the immune response
at all levels.  This includes support for molecular biological
studies on gene expression, gene recombination and interactions among
different parts of the immune system to control the overall response
to a stimulus. The scope of research to be supported under this PA
includes, but is not limited to, the following broad areas of
interest and specific examples of investigations.
o  definition of pathways that regulate gene activation and intra- or
extra-cellular signals that control gene rearrangements in the immune
o  elucidation of the control of the immune system antigen receptor
repertoire to prevent autoimmune reactivity;
o  further definition of interactions of immune system molecules to
initiate and maintain an effective immune response;
o  continued mapping of genes activated in cells of the immune
o  further definition of the processes that control immune cell
differentiation and development;
o  determination, at the cellular and molecular levels, of the
central nervous system modulation of the immune response;
o  determination of the role of bidirectional signaling between T
cells, B cells, antigen presenting cells and other immune system
cells in normal and abnormal immune responses;
o  elucidation of the function of antigen processing, presentation
and costimulation in establishing the local microenvironment
necessary for activation and establishment of effector functions; and
o  elucidation of the cellular and molecular bases of age-related
changes in immune regulation.
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 of the purpose of the research.  This policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
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 the NIH
Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994.
Investigators may obtain copies from these sources or from the
program staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
Applications are to be submitted on the grant application for PHS 398
(rev. 5/95) and will be accepted on the standard application
deadlines as indicated on 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:
For purposes of identification and processing, item 2 on the face
page of the application must be marked "YES".  The PA number and the
PA title must also be typed in section 2.
The completed, signed original and five (5) legible, single-sided
copies of the application must be sent or delivered to:
BETHESDA, MD 20892-7710
BETHESDA, MD 20817-7710 (for express/courier service)
R29 applications must include at least three (3) sealed letters of
reference attached to the face page of the original application.
FIRST applications submitted without the required number of reference
letters will be considered incomplete and will be returned without
Applicants from institutions that have a General Clinical Research
Centers (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the Center as a resource for
conducting the proposed research.  If so, a letter of agreement from
the GCRC Program Director must be included in the application
Review Procedures
Applications will be assigned on the basis of established PHS
referral guidelines. Upon receipt, applications will be reviewed for
completeness by the NIH Division of Research Grants. Incomplete
applications will be returned to the applicant without further
consideration.  Applications will be reviewed for scientific and
technical merit by study sections of the Division of Research Grants,
NIH, in accordance with the standard NIH peer review procedures.
As part of the initial merit review, all applications will receive a
written critique and 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,
assigned a priority score, and receive a second level review by the
appropriate national advisory council.
Review Criteria
The five criteria to be used in the evaluation of grant applications
are listed below.  To put those criteria in context, the following
information is contained in instructions to the peer reviewers.
The goals of NIH-supported research are to advance our understanding
of biological systems, improve the control of disease, and enhance
health.  The reviewers will comment on the following aspects of the
application in their written critiques 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 by the reviewers 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 a 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.
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
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?
The initial review group will also examine: the appropriateness of
proposed project budget and duration; the adequacy of plans to
include both genders and minorities and their subgroups as
appropriate for the scientific goals of the research and plans for
the recruitment and retention of subjects; the provisions for the
protection of human and animal subjects; and the safety of the
research environment.
Applications will compete for available funds with all other
favorably recommended applications.  The following will be considered
when making funding decisions:  quality of the proposed project as
determined by peer review, program balance, and availability of
Written and telephone inquiries are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
Inquiries regarding programmatic (research scope and eligibility)
issues may be directed to:
Stephen M. Rose, Ph.D.
Chief, Genetics and Transplantation Branch
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases Solar Building,
Room 4A14
6003 Executive Blvd.
Bethesda, MD 20892-7640
Telephone: (301) 496-5598
FAX:  (301) 402-2571
EMAIL:  sr8j@nih.gov
Anna M. McCormick, Ph.D.
Chief, Biology Branch
Biology of Aging Program
National Institute on Aging
Gateway Building, Suite 2C231
Bethesda, MD  20892
Telephone:  (301) 496-6402
FAX:  (301) 402-0010
Internet: am38k@nih.gov
Walter S. Stolz, Ph.D.
Director, Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
Natcher Building, Room 6As-25C
Bethesda, MD  20892-6600
Telephone:  (301) 594-8834
FAX:  (301) 480-3505
Email:  stolzw@ep.niddk.nih.gov
Susana Serrate-Sztein, M.D.
Chief, Arthritis Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS37G
Telephone:  (301) 594-5032
FAX:  (301) 480-4543
Email:  szteins@ep.niams.nih.gov
Direct inquiries regarding fiscal matters to:
Laura Eisenman
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases Solar Building,
Room 4B23
6003 Executive Blvd.
Bethesda, MD 20892-7610
Telephone: (301) 496-7075
FAX:  (301) 480-3780
Email:  le55d@nih.gov
Mr. Joseph Ellis
Grants Management Officer
Grants and Contracts Management Office
National Institute on Aging
Gateway Building, Suite 2N212
Bethesda, MD  20892
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Internet:  je14j@nih.gov
Nancy Dixon
Grants Management Officer
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Natcher Building, Room 6An-44C
National Institutes of Health
Bethesda, MD  20892-6600
Telephone:  (301) 594-8854
FAX:  (301) 480-3504
email:  dixonn@ep.niddk.nih.gov
Ms. Carol Fitzpatrick
Grants Management Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS43K
Telephone:  (301) 594-3506
FAX:  (301) 480-4543
Email:  fitzpatric@ep.niams.nih.gov
This program is supported under authorization of the Public Health
Service Act, Sec. 301(c), Public Law 78-410, as amended.  The
Catalogue of Federal Domestic Assistance Citation is No. 93.855 -
Immunology, Allergy, and Transplantation Research, No. 93.366  -Aging
Research, No. 93.847 - Digestive Diseases and Nutrition, No. 93.848 -
Diabetes, Endocrinology and Metabolic Diseases, No. 93.849 -Kidney,
Urologic and Hematologic Diseases, and No. 93.846 -Arthritis,
Musculoskeletal and Skin Diseases Research.  Awards will be
administered under PHS grants policies and Federal Regulations 24 CFR
Part 52 and 45 CFR Part 74.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems 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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