This is 2nd part of long NIH grant. Can be ignored. Judy


RESEARCH OBJECTIVES

Background

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
immunodeficiencies.

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.

Scope

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
system.

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.

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 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.

APPLICATION PROCEDURES

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 301/435-0714, email:
[log in to unmask]

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:

DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
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
review.

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
material.