kristoff@NET.BIO.NET (Dave Kristofferson) (11/19/89)
RFA: 89-HD-08
GENETICS AND BIOCHEMISTRY OF CELL FATE DETERMINATION IN
DEVELOPMENT; CYTOPLASMIC DETERMINANTS, CELLULAR
INDUCTION AND GENOMIC IMPRINTING
P.T. 34; K.W. 1002019, 1003002, 1002004, 1002059
NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
Application Receipt Date: February 8, 1990
The Genetics and Teratology Branch (GTB) of the Center
for Research for Mothers and Children (CRMC) of the
National Institute of Child Health and Human Development
(NICHD) invites research grant applications for studies
on the genetics and biochemistry of cell fate determina-
tion in development. By issuing this request for
applications (RFA), the Branch is encouraging investi-
gators' interest in a research emphasis area important to
the Institute's mission.
BACKGROUND
The phenotypic fate of an individual cell within a
developing organism can be determined quite early in its
developmental program. While the ultimate phenotypic
fate of any given cell results from the integration of
several different biological processes, including cell
migration, cell interaction, and tissue specific gene
expression, certain early developmental events have
enormous influence on the developmental potential of that
cell. Questions concerning the nature of such early
developmental events have been, and continue to be, one of
the central unresolved issues in developmental biology.
Experiments that are now classic have demonstrated that
material contained in the egg prior to fertilization can
have a direct impact on developmental outcome. Studies
that have reoriented, removed, or transplanted portions
of cytoplasm have demonstrated that determinants exist
within that cytoplasm that can influence the phenotypic
fate of cells within the developing organism. Adjacent
cells have been shown to influence the fate of their
immediate neighbors by inducing particular responses.
More recent experiments have demonstrated that the
ability of a particular gene to express at all, and have
any impact on cell fate, can be "preprogrammed" in the
parental generation. Thus, the physical orientation of
the embryo, the determination of germ layers, or the
determination of specific cell phenotypes can be
directed by one or more of these biological processes.
Clearly, the failure of any of these processes to
operate normally could lead to developmental anomalies.
Therefore, NICHD encourages studies on the genetic and
biochemical basis of cell fate determination which could
lead to a better understanding of normal development and
to the prevention of congenital malformation in the
future.
The purpose of this RFA is to stimulate and encourage
research directed at defining the underlying genetic
basis, biochemical nature, and molecular mode of action
of the processes that can influence cell fate, including
cytoplasmic determinants, induction, and genetic imprint-
ing. While our major interest rests in how such
processes operate during mammalian development, other
experimental model systems that can contribute to our
understanding of the fundamental principles that apply
to human development are strongly encouraged.
The National Institute of General Medical Sciences (NIGMS)
also supports research leading to an understanding
of fundamental principles underlying genetics and
cell biology, especially in model systems. Therefore,
a secondary assignment to NIGMS for applications
responsive to this RFA might be appropriate. It is
realized that additional descriptive work is needed to
expand the field. However, investigators are encouraged
to suggest approaches that characterize the biological
nature of these processes at the molecular level,
including the identification of the molecules involved,
their genetic regulation, their functional roles, and
their mode of action.
This initiative has important implications for both basic
science and clinical studies. The information expected
from these investigations will further our understanding
of the specific molecules involved in establishing cell
fate, how they are regulated, and how they function. In
addition, underlying principles that direct normal
patterns of growth, differentiation and morphogenesis
and against which aberrations of these processes can be
understood will be further defined. In a clinical
context, these studies provide the basis for an improved
understanding of the possible causes of birth defects
and other developmental abnormalities that lead to early
embryonic wastage and spontaneous abortion.
RESEARCH GOALS
The primary goal of this RFA is to support a group of
projects that are devoted to the investigation of the
genetics and biochemistry of cell fate determination
during development. It is expected that the latest
molecular biological and molecular genetic technologies
will be employed, including the generation of appropriate
reagents and either chimeric or transgenic animals, if
appropriate. Particular program interest includes, but
is not limited to, such issues as:
o Identification and molecular characterization of
specific cytoplasmic determinants
o Identification, characterization, and mode of
action of molecules responsible for the localization of
determinants within the cytoplasm
Such molecules could include architectural or
anchorage components that are responsible for maintaining
localized concentrations of specific determinants.
o Elucidation of mechanisms that maintain functional
gradients of cytoplasmic determinants either by regulating
absolute levels of the molecules or their functional
expression
o Elucidation of possible cascade events that together
are responsible for the localized expression of cell
fate-determining molecules
o Identification and characterization of endogenous
molecules with specific inductive capabilities
o Investigation of the genetic regulation of either
cytoplasmic or inductive determinants
Such studies could include classic studies involving
the genetic transmission of such molecules or the analysis
of mutants with abnormal expression. In addition,
molecular genetic approaches could be employed, including
the isolation of specific genes and the identification of
sequences responsible for localized expression.
o Investigation of mechanisms responsible for the
genetic imprinting of certain genes
MECHANISM OF SUPPORT
Applications in response to this RFA will be funded
through the traditional individual research award
program of NICHD (R01 and R29). This announcement
is for a single competition with the deadline for
receipt of applications February 8, 1990. The
earliest possible start date for grants would be
December 1, 1990. It is anticipated that four (4)
grants will be awarded under this program,
contingent upon receipt of a sufficient number
of meritorious applications and the availability
of funds.
REVIEW PROCEDURES AND CRITERIA
Applications will be reviewed by NICHD staff for respon-
siveness to the RFA. Applications judged to be
nonresponsive will be returned. The applicant may
resubmit the application and have it assigned for
review in the same manner as unsolicited grant applica-
tions. An application will be considered nonresponsive
to this RFA if it is identical to one already submitted
to the NIH for review, unless the previous application is
withdrawn.
Responsive applications may be subjected to a triage by a
peer-review group to determine their scientific merit
relative to the other applications received in response to
this RFA. NIH will withdraw from competition those
applications judged to be noncompetitive and notify the
applicant and institutional business official. Those
applications judged to be competitive will be further
evaluated for scientific/technical merit by a review group
convened during June 1990 solely for this purpose by the
Scientific Review Program, NICHD. Criteria for the initial
review include the significance and originality of research
goals and approaches; the feasibility of research and
adequacy of the experimental design; the research
experience and competence of the investigator(s)
to conduct the proposed work; the adequacy of investiga-
tor(s) effort devoted to the project; and the appropriateness
of the project duration and cost relative to the
work proposed. Following review by the Initial Review
Group, applications will be evaluated by the Institutes'
Advisory Council for program relevance and policy issues
before awards for meritorious proposals are made.
APPLICATION PROCEDURE
Applications should be submitted on Form PHS 398 (rev. 10/88),
available in business or grants offices at most academic
research institutions or from the Division of Research
Grants, NIH. The phrase RFA 89-HD-08:
GENETICS AND BIOCHEMISTRY should appear in item 2 of
the face page and the "Yes" box should be
checked. The RFA label available in the October 1988
version of Form PHS 398 must be affixed to the bottom
of the face page. Failure to use this label could
result in delayed processing of your application
such that it may not reach the review committee in time
for review. The original and four (4) copies
should be sent to:
Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, Maryland 20892**
In addition to the five copies sent to the Division of
Research Grants, two (2) copies of the application
should be sent to:
Laurance Johnston, Ph.D.
Scientific Review Program
National Institute of Child Health
and Human Development
Executive Plaza North, Room 520A
Bethesda, Maryland 20892
Any inquiries about this RFA should be directed to:
Joel M. Schindler, Ph.D.
Genetics and Teratology Branch
Center for Research for Mothers and Children
National Institute of Child Health
and Human Development
Executive Plaza North, Room 643C
Bethesda, Maryland 20892
(310) 496-554l
This program is described in the catalog of Federal
Domestic Assistance No. 13.865, Research for Mothers
and Children. Awards will be made under the authority
of the Public Health Service Act, Section 301 (42 USC241),
and administered under PHS grant policies and Federal
Regulations 42 CFR Part 52 and 45 CFR Part 74. This
program is not subject to review by a Health Systems
Agency.
RFA AVAILABLE: 90-HL-4-H
SPECIALIZED CENTERS OF RESEARCH (SCOR) IN ARTERIOSCLEROSIS
P.T. 04; K.W. 0715040, 0710030, 0755030, 0745027
National Heart, Lung, and Blood Institute
Application Receipt Date: December 3, 1990
INTRODUCTION
The Division of Heart and Vascular Diseases (DHVD) of the
National Heart, Lung, and Blood, Institute (NHLBI) invites
new and renewal grant applications to enter into a single
open competition for Specialized Centers of Research in
Arteriosclerosis (SCOR/A). In keeping with the criteria for
Centers, the solicitation requires all applicants to propose
both basic and clinical research. The goal of the program is
to advance understanding of the causes and mechanisms of
atherogenesis and through this knowledge improve prevention,
diagnosis and treatment in patients afflicted with this
disease.
The aim of this request for applications is to solicit and
support interdisciplinary programs focusing on particularly
promising areas of investigation in arteriosclerosis
research. The solicitation is designed to further diversify
the SCOR/A program and to encourage new applicants.
Arteriosclerosis is a family of pathological processes and is
strongly influenced by abnormalities of lipid and lipoprotein
metabolism. However, lipoprotein metabolism is only part of
the disordered vascular biology that results in
atherosclerosis. Other important elements in the
pathogenesis and natural history of arteriosclerosis interact
with or exert effects independent of lipid changes. These
include the roles the arterial wall cells play in response to
lipids; the coordination of vascular cellular events
following stimulation to yield plaques of various types; the
cellular and molecular biology of relevant participating
cells and their regulatory systems; vascular developmental
biology and vascular and metabolic responses to atherogenic
stimuli; the roles of the thrombotic process in all aspects
of atherogenesis; and the healing or regression of
atherogenesis. The NHLBI wishes to encourage efforts to use
molecular genetic approaches to identify and characterize
those genes that may interact with or are independent of
genes related to lipid metabolism that may play a major role
in the causation of atherosclerosis.
BACKGROUND
Arteriosclerosis is a complicated disease with an
incompletely understood etiology. An interdisciplinary
approach to this disorder is required, and the SCOR/A program
has provided a focus for this particular approach to
understanding the disorder. The SCOR/A has been and remains
a particularly responsive and productive mechanism for
meeting the needs of arteriosclerosis research. It was
initiated in 1971 as a special program mechanism to extend
the "state-of-the art" of research on arteriosclerosis and to
apply research findings to disease prevention and control.
The SCOR/A program has pioneered new directions of research,
enlisted skills and disciplines not previously associated
with research on arteriosclerosis and attracted able
investigators to the field. The Centers have addressed
arteriosclerosis as a multifactorial disease and promoted
multidisciplinary research on the relationships of
hyperlipidemia, hypertension, thrombosis, diabetes, smoking,
and other risk factors and diseases to the etiology and
pathogenesis of arteriosclerosis. The Centers have attained
preeminence in research on lipid and lipoprotein metabolism,
and in studies of the structure and function of lipoproteins
and apoproteins. The program has established extensive non-
human primate resources to focus on lesion
progression/regression. Other active research areas include
nutrition, lipid and lipoprotein metabolism, biobehavioral
research, and studies on the relationship of hemodynamics to
atherogenesis. The SCOR/A fostered research on pediatric
arteriosclerosis, and initiated demonstration and education,
and behavioral and psychosocial research in the area of risk
factor reduction. The program also pioneered affiliations
with biomedical engineering laboratories to develop
computer-assisted x-ray processing technology and non-
invasive instrumentation for the detection and assessment of
lesion progression and regression. Many of the studies
pioneered by SCOR/A are currently supported by other program
mechanisms in the Institute.
An unusual attribute of the SCOR/A program has been the
ability to undertake studies which are of long duration.
Such studies have extended over several of the five year
project periods of the Centers and are not generally
supported by other mechanisms of grant support. These have
included a study in non-human primates of lesion regression
in advanced atherosclerosis, the breeding of animal models
for selected risk factor traits, and a multiple drug-diet
trial to determine whether marked reductions of serum lipid
levels in individuals with familial hypercholesterolemia will
result in the regression of arterial lesions.
A further special and important attribute of the SCOR/A is
that the Centers function collectively as a program. Several
of them participate in collaborative studies with other
SCOR/A Centers. There is an annual 2 day SCOR/A scientific
meeting attended by 80 to 100 investigators and an annual
joint Institute-SCOR Directors meeting for planning purposes.
NHLBI also fosters scientific exchange by providing
to the investigators a compilation of the annual SCOR
progress reports. These activities, together with
collaboration outside of the SCOR/A, have extended the
research capabilities of the individual Centers.
The current SCOR/A Program consists of six Centers and one
National Research and Demonstration Center (NRDC)
representing the fourth generation of the SCOR/A (1986-1991).
In addition to conducting the research described above, the
current program also has included the cellular biology of
atherogenesis; studies on the role of the endothelial cell in
relation to procoagulant and anticoagulant activities;
lipoprotein modification and lipoprotein-associated
prostaglandin synthesis; studies on the mechanisms of
macrophage vascular wall infiltration and lipid accumulation;
ultrastructural studies of cells; and the assembly and
biosynthesis of lipoproteins and matrix. New studies have
also been undertaken to define genetic markers and the role
of non-traditional risk factors for arteriosclerosis. There
remain numerous research opportunities in arteriosclerosis,
and the comprehensive and multidisciplinary nature of the
SCOR/A program is well suited for their exploitation.
OBJECTIVES AND SCOPE
Anticipating the most critical areas of research in
arteriosclerosis during the 1990's that might benefit from
SCOR support, more emphasis should be brought to bear on
certain problems than is presently the case in the SCOR/A
program. Also, since clinical investigation is
important to research in arteriosclerosis, the program would
benefit from an increase in such activity. The
multidisciplinary collaborative atmosphere of a SCOR is
suited to provide the impetus to translate basic studies into
clinically useful diagnostic and therapeutic tools.
An essential element in a SCOR program in arteriosclerosis is
the integration of fundamental studies of pathophysiologic
mechanisms with studies in patients. The program should,
therefore, provide an opportunity to integrate studies at
various levels, e.g. molecular, cellular, structural and
functional with abnormalities observed clinically.
Additionally, the SCOR program should offer an opportunity to
investigate mechanisms involved in the sequelae to a clinical
intervention and to perform studies designed to provide a
rationale for the choice of pharmacologic agents or dietary
regimens.
In the past the SCOR/A have played a prominent role in
fostering research in demonstration and education and
behavioral modification, beginning with the Stanford Three
Community Study and continuing with similar activities in
National Research and Demonstration Centers. In the meantime
NHLBI has developed a substantial program of
demonstration and education research, a Behavioral Medicine
Branch with a regular grant program, and other activities such as
the National Cholesterol and the National High Blood Pressure
Education Programs. There now is no need for such
activities in the SCOR/A program, so they will neither be
solicited nor accepted.
AREAS OF OPPORTUNITY
The past decade has seen astonishing progress in molecular
and cellular biology including molecular genetics and gene
manipulation. These technologies could find wide application
to areas of interest in arteriosclerosis, such as systemic
and local lipid metabolism; thrombotic processes; the
biology, pathobiology and pharmacology of the vessel wall;
and the concepts of resistance and susceptibility to lesion
development. Moreover, there have been great gains in
characterizing and utilizing comparative models of
atherogenesis and in the ability to study cell-cell
communication, differentiation and interaction. The
application of these technologies to cells, tissues and
organs and especially to plaque building and regression can
be exploited by the SCOR/A.
This solicitation is designed to emphasize research that is
directed toward fundamental mechanisms in atherogenesis and
new approaches to disease prevention, diagnosis and
treatment. A mutually supportive interaction between basic
scientists and clinical investigators will be essential. The
individual projects should be correlative or complementary
in terms of the topic or topics chosen by the applicant.
Each SCOR must represent a multidisciplinary approach to both
clinical and laboratory research focused on particular
problems within the field of arteriosclerosis.
Although research programs will vary with local talent,
interest, and resources, each SCOR should have a central
theme to which all individual projects relate and which
serves as an integrating force. Emphasis in proposed
projects should be on the development of innovative
approaches, the elaboration of new and significant
hypotheses, and the generation of novel strategies.
Collaborative research between different institutions may be
proposed when appropriate. New applicants are strongly
encouraged to participate in this competition.
The following brief discussion is intended to offer a few
examples of research sought and to emphasize the importance
of employing a wide spectrum of basic and clinical approaches
in the SCOR environment to addressing these important
problems. These areas have been identified by members of the
arteriosclerosis research community including Advisory
Committee members and Institute Staff; however, they are not
all-inclusive. Investigators are strongly urged to consider
other relevant projects and approaches not mentioned below.
o Lipid interactions with the vessel wall
The basic mechanisms involved in the initiation of the
atherosclerotic lesion as well as those events that
sustain and lead to progression are not very well
understood. Lipoprotein metabolism by the arterial
wall, and other tissues in vivo and ex vivo are areas
that need further investigation. Of importance are
measurements to quantify the kinetics of lipoprotein
uptake, residence time, and rates of degradation with
special emphasis on the contribution of individual
resident cell types. Quantitative measurements of these
early events could provide tools that might be used to
test strategies and therapeutic modalities that could be
used to inhibit or reverse the early lesions. The use
of molecular biological approaches coupled with basic
studies of molecular genetics/gene regulation and their
possible use as a cross-over to clinical investigations
would be of great interest.
o Pathogenesis of plaques
Investigation of basic mechanisms of plaque formation, and
elements involved therein, is encouraged. This
includes, but is not limited to: vascular biology and
metabolism involving smooth muscle cells, endothelial
cells, and the extracellular matrix; the rheology of
blood flow; elements of inflammation; leukocytes,
lymphocytes and other blood components; and macrophage
biology. Pharmacological probes may prove useful to
study mechanisms of atherogenesis.
o Receptor physiology
Hormones and other ligands are known to regulate their
own receptors, but it has only recently been recognized
that receptors can determine the concentrations of their
own ligand. The most clear-cut example occurs in the
LDL receptor system. Increasing the number of receptors
will decrease the level of the circulating ligand.
Novel approaches to effect changes in receptor
levels are highly desirable. The development of
transgenic animal models and gene transfer studies may
prove useful tools to study receptor biochemistry and
physiology.
o Cellular and metabolic responses to challenge
An area that will benefit from further attention is the
genetic basis of factors that determine sensitivity and
resistance to atherosclerosis as well as differences
in the response to dietary challenge. Emphasis on the
diversity of responses could be investigated in
mechanistic studies of nutritional challenges that could
include oxidized sterols and fatty acids of varied chain
lengths and degrees of saturation. Studies of age-
related phenomena are also needed.
o Gene regulation
Apolipoprotein genetic variation plays a major role in
determining human genetic susceptibility to
atherosclerosis. In the last few years, cDNA and genomic
clones have been derived for the apolipoproteins. The
apolipoprotein genes have been mapped in the human
genome and mutations in the human genes have been
identified at both the amino acid and DNA levels. Some
of these mutations have profound effects on lipoprotein
metabolism and are associated with premature
atherosclerosis. Yet, it is not well determined how
their expression is regulated and whether other
regulatory factors exist that might have clinical
significance.
o Genetic studies of premature atherosclerosis
The goal of this research is to characterize the genes
and their products that contribute significantly to the
development of premature atherosclerosis. Several
studies have indicated that familial aggregation for
coronary heart disease (CHD)
may be associated with genetic predispositions not
adequately explained by the traditional risk factors.
In some patients, CHD is the result of a single gene
defect such as in familial hypercholesterolemia.
However, most CHD fits best into a multifactorial
category where the interaction of multiple genes with
multiple environmental factors produces the familial
aggregation. The number of genes involved may be large
for a complex disorder such as CHD, in which plasma
lipoproteins, the coagulation system, the cellular
elements and other components of the blood and arterial
wall all play a part.
A primary objective of this line of research would be to
undertake segregation analyses and genetic linkage
studies in families with premature atherosclerosis,
employing classical genetic methodology and molecular
biologic techniques. Additional objectives would be
to: phenotype individual family members for selected
characteristics; develop additional phenotypic markers
according to the interests of the investigator; and
establish a collection of DNA obtained from each
phenotyped family member, that will be made available to
other SCOR investigators and ultimately to the
scientific community. Arrangements for collaborative
efforts among institutions are considered appropriate to
satisfy the objectives of this line of research.
o Vascular developmental biology
Research to discover fundamental mechanisms of
developmental biology underlying atherogenesis is of
particular interest. This would include investigations
of the relationship of cell proliferation to
differentiation at the molecular level and the
formation of the vessel wall during embryogenesis.
Several current issues in vascular developmental biology
merit particular consideration. These include factors
controlling endothelial and smooth muscle cell growth
during development; mechanisms controlling
differentiation of the cells of the vessel wall from
primitive mesenchyme; factors controlling genetic
diversity of the cells of the vascular wall; the role of
endothelial cells in smooth muscle differentiation and
modulation; the formation of vascular intimal cells and
their relationship to medial smooth muscle cells and
localization of atherosclerosis; and the role of
developmental mechanisms in the ontogeny of the
hypertensive vasculature.
o Atherogenesis and thrombotic processes
Several issues implicating the hemostatic system in
atherogenesis merit consideration. These include
possible links between plasma lipoproteins and the
coagulation factors; studies of the relative
contributions of lipid and non-lipid atherogenic and
thrombotic factors in selected lipid disorders in vivo;
interactions of coagulation factors with lipoprotein
subspecies, possibly including their effect on the
function of the endothelial cells, blood cells and
platelets; mechanisms regulating the interaction of
blood components with the vascular endothelium,
including the roles of peptide regulatory factors and
eicosanoids in thrombosis and atherogenesis; factors
regulating endothelial functions such as macromolecular
transport and abnormal permeability; and mechanisms
controlling the arterial endothelial thrombo-resistance
processes.
The foregoing account is intended to provide examples of
research that are appropriate for the SCOR mechanism.
Applicants should design programs based on their own
knowledge of the fields, their perceptions of research
needs, and the feasibility of research in those areas. While
lipid phenomena continue to be central, the examples cited
are in keeping with concepts and technologies of research for
the next decade. However, the intention to emphasize
research exploiting the use of molecular biological
approaches, molecular genetics/gene regulation, vascular
biology and metabolism, physiology of the response to
challenge and use of pharmacological probes to study
mechanisms of atherogenesis, will require efforts by
investigators not previously associated with research on
arteriosclerosis and offers the opportunity for the
establishment of new centers.
ELIGIBILITY CRITERIA
In addition to the standard criteria defining eligibility for
Public Health Service grants, the applicant organization must
be, or must be associated with, a major medical institution.
All elements of a
program must include, and be subjected to, stringent and
critical evaluative procedures. Women and minority
individuals should be included in the study population,
otherwise a clear rationale for their exclusion must be
provided in the application.
Universities and medical schools, hospitals and public or
private research institutions, alone or in combination, with
appropriate research and clinical capabilities to meet the
objectives of this SCOR program are encouraged to respond to
this solicitation.
EXCLUSIONS
The fourth competition for the SCOR/A program, announced in
1984, provided the opportunity for the SCORs to extend the
results of basic and clinical research to the community by
integrating demonstration and education research and
competing as National Research and Demonstration Centers
(NRDC). This option will NOT be available for the present
competition. Investigators interested in pursuing
demonstration and education research in the topic area of the
SCOR/A are requested to contact NHLBI Staff to discuss
options.
No support will be provided under the SCOR funding mechanism
for largely epidemiological programs or programs containing
exclusively clinical or exclusively basic studies. While the
development of new instrumentation may be part of the SCOR,
support for development alone will not be provided.
Institute staff should be consulted if an applicant plans to
request funds to purchase and install expensive new
equipment.
Applicants should be aware that applications for supplemental
funds will be accepted only under unusual and well defined
circumstances. For example, NHLBI may provide
supplements to centers to continue a project not funded for
the entire project period. NHLBI staff should be
consulted prior to submission of an application.
Supplemental grants for these purposes will not be awarded
for the first 18 months or the last 12 months of a total
project period.
MECHANISM OF SUPPORT
The support mechanism will be the research grant-in-aid (P50) for a
period of five years commencing December 1, 1991. However,
it will differ from other research grants in that there will
be required communication between SCORs, usually in the
setting of a biennial combined meeting of SCOR participants.
Therefore, in preparing the budget, applicants
should request travel funds for this purpose in fiscal years
1992, 1994, and 1996 of the budget.
Applicants are expected to furnish their own estimates of the
time required to achieve specific objectives of the proposed
work, a schedule for completion of the work, and an outline
of the segments into which the proposed program can be
logically divided. The SCOR will plan, direct, and execute
its own research program, but any substantial modification in
the scope or objectives that may be approved for funding must
be mutually agreed upon by the SCOR Director and the NHLBI.
Although this solicitation is included in the plans for
Fiscal Year 1992, support of grants pursuant to this request
for applications is contingent upon ultimate receipt of funds
for this purpose. It is anticipated that approximately 10
SCORs will be funded under this RFA for a total annual cost
(direct and indirect) of about $20 million. The level of
funding of the individual SCORs will be influenced by the
overall merit of proposals, the level of support recommended
during the initial scientific review, and the amount of funds
available to the Institute. Since a variety of approaches
may be responsive to this solicitation, it is anticipated
that there will be a range of costs among individual grants
awarded.
Applications for new SCOR grants may request up to $1.0
million direct costs in the 01 year with a maximum of 4
percent annual escalation thereafter. Competing renewal
applications for SCOR grants may request up to $1.0 million
direct costs or 10 percent increase in direct costs over the
last noncompeting year, whichever is greater, in the first
year of renewal, with a maximum of 4 percent annual
escalation thereafter. Applications which exceed these
limits will be returned. Requests for special equipment
which cause the applications to exceed these limits,
however, will be permitted and considered on an individual
basis. CONTACT NHLBI STAFF IF YOU HAVE ANY QUESTIONS.
REVIEW PROCEDURES AND CRITERIA
SCOR/A applications will be reviewed and evaluated in a
single national competition. The initial phase of peer
review will be conducted by a group of predominantly non-
federal consultants and may involve a site visit. A second
level of review will be performed by the National Heart,
Lung, and Blood Advisory Council.
The applicant is not permitted to revise the application (no
additions or deletions of projects, cores or studies) after
submission to the Division of Research Grants. Projects
and/or cores within a SCOR grant may not be modified or
withdrawn during the review process. All projects and/or
cores reviewed at a site visit, will be included in the site
visit report when the application is evaluated by the Parent
Review Committee and also in the summary statement, when it
is considered by the Institute's Advisory Council.
The major factors to be considered in the evaluation of
applications include:
The qualifications, experience and commitment of
the SCOR Director and his/her ability to devote
adequate time and effort to provide effective
leadership;
the scientific merit of each proposed project
including the originality, feasibility of the
approach, and the adequacy of the experimental
design;
the competence of the investigators to accomplish
the proposed research goals, their commitment, and
the time they will devote to the program;
the integration of the interdisciplinary efforts
into a coherent enterprise with adequate plans for
interaction and communication of information and
concepts among the collaborating investigators;
the technical merit and justification of each core
unit;
the adequacy of facilities to perform the proposed
research including the laboratory and clinical
facilities, access to subjects, instrumentation,
and data management systems when needed;
the scientific and administrative structure of the
program, including adequate internal and external
arrangements and procedures for monitoring and
evaluating the proposed research and for providing
ongoing quality control and scientific review;
the institutional commitment to the program and the
appropriateness of the institutional resources and
policies for the administration of a research
program of the type proposed; and
the appropriateness of the budget for the proposed
program.
METHOD OF APPLICATION
Letter of intent: Prospective applicants are asked to submit
a letter of intent to apply to this RFA. This letter should
include the names of any participating institutions and all
investigators, together with a descriptive title. Such a
letter of intent is not binding and will not enter into
the review of any application subsequently submitted, nor is
it a necessary requirement for application. Letters of
intent are requested solely for planning purposes. The NHLBI
Staff will not provide responses to such letters. Letters of
intent to apply to this RFA should be received no later than
April 15, 1990 and should be addressed to:
Dr. Charles L. Turbyfill
Review Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 553
Bethesda, Maryland 20892
Format for Applications: Submit applications on form PHS-398
(revised 10/88), the application form for the traditional NIH
research project grant. Copies of this form are available in
the applicant institution's office of sponsored research, or
may be obtained from the following:
Office of Grants Inquiries
Division of Research Grants, NIH
Westwood Building, Room 449
NIH, Bethesda, Maryland 20892
The NHLBI has prepared Supplemental Guidelines to delineate
important areas where the regular instructions are modified
or supplemented. Because of the unique features and goals of
the SCOR Program, applicants will require these Supplemental
Guidelines to prepare an acceptable application. Copies may
be obtained from the address listed below under Inquiries.
To identify the application as a response to this RFA, CHECK
"YES" on item 2 of page 1 of the application and enter the
title "Specialized Centers of Research in Arteriosclerosis"
and enter the RFA number NIH-90-HL-4-H in the space provided.
THE RFA LABEL FOUND IN THE FORM PHS-398 APPLICATION KIT MUST
BE AFFIXED TO THE BOTTOM OF THE FACE PAGE OF THE ORIGINAL
COMPLETED APPLICATION FORM PHS-398. FAILURE TO USE THIS
LABEL COULD RESULT IN DELAYED PROCESSING OF YOUR APPLICATION
SUCH THAT IT MAY NOT REACH THE REVIEW COMMITTEE IN TIME FOR
REVIEW.
Application Procedure: Send or deliver the completed, signed
application and four (4) complete photocopies of it to the
following, making sure that the original application with the
RFA label attached is on top:
Division of Research Grants
Westwood Building, Room 240
National Institutes of Health
Bethesda, Maryland 20892**
SEND TWO ADDITIONAL COPIES OF THE APPLICATION TO DR. CHARLES
TURBYFILL AT THE ADDRESS LISTED UNDER "LETTER OF INTENT". IT
IS IMPORTANT TO SEND THESE TWO COPIES AT THE SAME TIME AS THE
ORIGINAL AND FOUR COPIES ARE SENT TO THE DIVISION OF RESEARCH
GRANTS, OTHERWISE THE NHLBI CANNOT GUARANTEE THAT THE
APPLICATION WILL BE REVIEWED IN COMPETITION FOR THIS RFA.
Applications must be received by December 3, 1990. An
application not received by this date will be considered
ineligible.
Timetable:
Letter of Intent April 15, 1990
Application Receipt Date December 3, 1990
Review by National Heart, Lung
and Blood Advisory Council September, 1991
Anticipated Award Date December, 1991
Inquiries: Inquiries regarding this announcement may be
directed to:
Dr. Momtaz Wassef
Deputy Chief
Lipid Metabolism/Atherogenesis Branch
Division of Heart and Vascular Diseases
National Heart, Lung and Blood Institute
Federal Building, Room 4A12
Bethesda, Maryland 20892
(Telephone: 301-496-1978)
SUPPLEMENTARY INSTRUCTIONS
FOR THE ANIMAL RESOURCES PROGRAM
SMALL GRANTS PROGRAM IN LABORATORY ANIMAL SCIENCES
FORM PHS-398 (Rev. 10/88)
Applications must be submitted on the standard PHS research grant application
form (PHS-398, Rev. 10/88), following the instructions supplied with those
forms EXCEPT for the following:
SECTION 1
1. Face Page of Application
Item 2: Response to specific Program Announcement: "Yes". Write in:
"Small Grant Program in Laboratory Animal Sciences".
Item 8: Not applicable, leave blank
2. Application Page 4: Detailed Budget for the 12-Month Period. Funds
should be limited to the following categories: personnel (technical only),
supplies, travel, and small equipment items. All requests must be strongly
and SPECIFICALLY justified. The total request may not exceed $25,000 direct
costs. (Use Application Page 5 for explanation of the need for proposed
expenditures.)
3. Application Page 5: Budget Estimates for All Years. Not applicable; do
not complete. Instead use this page to justify budget requests for the one-
year project period.
4. Biographic Sketch: Not to exceed one page per individual. Include this
information for all professional personnel associated with this project as
collaborators, consultants, etc. Attach an appropriate letter from each
collaborator or consultant confirming his/her role in the project.
SECTION 2
1. Research Plan: Specific aims, background and significance and
experimental design and methods; not to exceed four pages. These sections of
the research plan are described in the PHS-398 (Rev. 10/88) grant application
kit instructions, and should be followed while keeping within the four page
limitation. Citations in this section are limited to one additional page
entitled: Literature Cited.
2. Appendix: Not applicable. Do not submit.
SUBMISSION OF THE COMPLETED APPLICATION FORMS:
Copies of applications should be sent to:
A. Division of Research Grants:
Mail or deliver the complete and signed, typewritten original application and
four copies, to the Division of Research Grants, as specified in the general
instructions.
B. Office of Review, Division of Research Resources:
In order to enable us to carry out expedited review of applications, please
mail two additional unstapled copies of the application to:
Dr. Arthur Schaerdel
Office of Review
Small Grants Program
Division of Research Resources, NIH
5333 Westbard Avenue, Room 10A16
Bethesda, MD 20892
Identify the mailing envelope for these two copies as containing a Small
Grant application.
Applications not following the above instructions, or not received in both
the Division of Research Grants and the Office of Review, DRR, by February 1,
will be returned to the applicant.
If you have questions, please call: Director, Laboratory Animal Sciences
Program, DRR at (301) 496-5175.