Full Text PAS-96-027
NIH GUIDE, Volume 25, Number 4, February 16, 1996
PA NUMBER:  PAS-96-027
P.T. 34


National Institute of Child Health and Human Development
The Jeffrey Modell Foundation
Application Receipt Dates:  June 1, October 1, 1996 and February 1,
The National Institute of Child Health and Human Development (NICHD)
of the National Institutes of Health (NIH), in collaboration with the
Jeffrey Modell Foundation (JMF), invites investigator-initiated
research grant applications for basic studies to identify the genes
and elucidate the molecular and genetic mechanisms that are
responsible for normal and defective development of the fetal,
neonatal, and infant/child immune system.
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), Developmental and Genetic Defects of Immunity, is
related to the priority areas of maternal and infant health, and
immunization and infectious diseases. 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) from
the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202-512-1800).
Applications may be submitted by domestic and foreign, 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.
Foreign institutions are not eligible for the First Independent
Research Support and Transition (FIRST) (R29) award. Racial/ethnic
minority individuals, women, and persons with disabilities are
encouraged to apply as Principal Investigators.
The mechanisms of support will be investigator-initiated research
project grant (R01) and FIRST (R29) awards.  Applications for FIRST
Awards and R01s from new investigators are particularly encouraged.
The total project period for an application submitted in response to
this PA may not exceed five years; and a foreign application may not
request more than three years of support.
The estimated funds available for the total (direct and indirect)
first-year costs of all awards made under this PA, for applications
assigned to the NICHD, will be $500,000 ($400,000 from the NICHD and
$100,000 from the JMF).  In Fiscal Year 1997, the NICHD and the JMF
plan to fund two to three R01 and/or R29 grants.  Awards and level of
support depend on receipt of a sufficient number of applications of
high scientific merit.  The usual PHS policies governing grants
administration and management, including indirect costs, will apply.
Although this program is provided for in the financial plans of the
NICHD and the JMF, awards pursuant to this program announcement are
contingent upon the availability of funds for this purpose. Funding
beyond the first and subsequent years of the grant will be contingent
upon satisfactory progress during the preceding years and
availability of funds.
New applications submitted for the June 1 and October 1, 1996 and
February 1, 1997 receipt dates will be eligible for funding under
this announcement.  Competing continuation applications for already
funded projects will NOT be eligible for awards from NICHD and JMF
under this PA.  Although the NICHD has a continuing interest in the
research areas of this PA, the latest anticipated award date with
set-aside funds is September 30, 1997.
An important mission of the NICHD is to conduct and support basic,
clinical and translational research on birth defects. This includes
basic research in developmental genetics and developmental
immunology.  Of particular interest to NICHD are studies that focus
on the ontogeny of immunity and the genetic defects that give rise to
inherited or primary immune deficiencies.  Currently, more than 70
primary immunodeficiencies of varying phenotypes and severity have
been described.  It has been estimated that approximately 500,000
individuals in the United States are affected, mostly with a mild
form.  There are, however, 5,000-10,000 individuals, primarily
infants and young children, with a severe, life-threatening form.
Because long term and/or intensive treatments are required, the total
medical, economic, and emotional impact on society is enormous.
Recently, more defective genes causing immunodeficiency have been
identified, cloned, and characterized.  However, they represent a
small percentage of the many defective genes responsible for primary
immunodeficiencies.  Moreover, the cellular, biochemical, genetic,
and molecular bases and mechanisms underlying most of the primary
immunodeficiencies have not been elucidated.
In recent years, the rapid advances in molecular biology and
molecular genetics provide the opportunity and technology for
identifying the defective genes and for elucidating the abnormal
genetic processes that cause the immunodeficiencies.  These advances
will also provide important information on normal genes and their
role and function in the development of the immune system.  Previous
studies of naturally-occurring human and experimentally-induced
animal "knockouts" have been extremely beneficial for identifying
defective genes and studying the mechanisms and factors in normal and
defective immune development.  One goal of this program announcement
is to encourage basic research that will lead to new and improved
diagnostic, therapeutic, and preventive strategies for primary
This program announcement was stimulated in part by a workshop on the
"Molecular Mechanisms of Primary Immunodeficiencies," which was
sponsored by the Developmental Biology, Genetics and Teratology
Branch of the NICHD.  The workshop revealed important gaps in our
knowledge and promising new opportunities and approaches for research
in the molecular and genetic mechanisms of normal immune system
development and primary immunodeficiencies.  The workshop was
sponsored partially by the JMF.  The JMF is a non-profit research
foundation devoted to primary immune deficiency.  It sponsors
symposia and workshops; supports research and training; and provides
diagnostic, clinical, informational, and educational services on
primary immunodeficiency disorders.  The JMF was established by Vicki
and Fred Modell in memory of their son Jeffrey, who died in 1986, at
the age of 15, of an inherited immune deficiency.
The objective of this PA is to encourage and promote new and
innovative research and approaches to identify the genes and
elucidate the molecular and genetic mechanisms responsible for normal
and defective development of the immune system.  The following are
examples of research topics that are appropriate for this PA;
however, they are not to be considered as exclusive or limiting:
o  Identify, clone, and characterize the genes important in the
normal ontogeny of the immune system as well as those mutant genes
which cause immunodeficiency.
o  Elucidate the cellular, biochemical, molecular and genetic
mechanisms underlying normal and defective development of the immune
o  Identify and characterize genes encoding specific proteins that
are critical for normal immune system development; identify those
mutant genes that alter expression of specific proteins and result in
defective immune system development and immunodeficiency.
o  Identify and characterize the genes and proteins involved in
cytokine-receptor signalling pathways; elucidate the molecular
mechanisms of signal transduction that are important in normal and
defective immune system development.
o  Identify and characterize X chromosome genes and their products
that are important for development of the immune system.
o  Identify MHC molecules and their genes that are important in
immune system development; and conversely, identify genetic mutations
that cause defects in the expression of MHC and defective immune
system development.
o  Develop animal models (natural and/or experimental) that will be
useful for studying the genes and genetic mechanisms responsible for
primary immunodeficiencies.
Applications submitted in response to this PA should focus on
identifying the genes and elucidating the basic mechanisms
responsible for normal development of the immune system and primary
immunodeficiencies.  The areas of interest listed above are not in
any order of priority.  They are only suggested examples of areas of
research to consider.  Applicants are encouraged to propose other
areas that are related to the objectives and scope of this PA.
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 is 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) and supersedes and strengthens the previous policies
(Concerning the inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.
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 20, 1994 (FR 59 14508- 14513) and reprinted
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.
Applications are to be submitted on the grant application form PHS
398 (rev. 5/95) and will be accepted on the standard application
deadlines as indicated in the application kit.  Requests for
continued funding of already funded projects (Type 2) will NOT be
considered under this program announcement. Applications may be
submitted for the following receipt dates only:  June 1, October 1,
1996 and February 1, 1997.  Awards resulting from this program
announcement will be made on or about April 1, July 1, and September
30, 1997.  Applications kits are available at most institutional
offices of sponsored research and may be obtained from the Grants
Information Office, Office 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 identification purposes, in item 2 of the application face page,
check the box marked "YES" and type in the number and title of this
program announcement.
The completed original and five legible copies must be sent or
delivered to:
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817-7710 (For express mail/courier service)
FIRST (R29) applications must include at least three 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
Center (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
Applications will be assigned on the basis of established PHS
referral guidelines.  Applications will be evaluated for scientific
and technical merit by an appropriate peer review group convened 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 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
o  scientific, technical, or medical significance and originality of
proposed research;
o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
o  qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research;
o  availability of the resources necessary to perform the research;
o  appropriateness of the proposed budget and duration in relation to
the proposed research;
o  adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
The initial review group will also examine the provisions for the
protection of human and animal subjects and the safety of the
research environment.
Applications assigned to the NICHD will compete for available
set-aside funds provided by the NICHD and the JMF.  The following
will be considered in making funding decisions:  quality of the
proposed project as determined by peer review, program priority and
balance among research areas of the program announcement, and
availability of funds.
Written and telephone inquiries are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
Direct programmatic inquiries to:
Allan Lock, D.V.M.
Developmental Biology, Genetics and Teratology Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B01, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-5541
FAX:  (301) 402-4083
Email:  LockA@HD01.NICHD.NIH.GOV
Direct fiscal inquiries to:
Mr. E. Douglas Shawver
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-1303
FAX:  (301) 402-0915
Email:  ShawverD@HD01.NICHD.NIH.GOV
This program is described in the Catalog of Federal Domestic
Assistance No. 93.865 - Research for Mothers and Children. 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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