Full Text HL-94-006

SPECIALIZED CENTERS OF RESEARCH - MOLECULAR GENETICS OF HYPERTENSION

NIH GUIDE, Volume 22, Number 45, December 17, 1993

RFA:  HL-94-006

P.T. 04

Keywords: 
  Hypertension 
  Molecular Genetics 
  0705048 


National Heart, Lung, and Blood Institute

Letter of Intent Receipt Date:  October 1, 1994
Application Receipt Date:  December 8, 1994

PURPOSE

The objective of this initiative is to establish a collaborative
network of closely interacting, multiproject Specialized Centers of
Research (SCORs) to study the molecular genetics of hypertension.
Three broad areas will be considered responsive to the initiative:
(1) mapping and identification of genes responsible for high blood
pressure or its complications in humans and in experimental animal
models; (2) mechanistic studies on the biological consequences of
variations in genes linked to hypertension or its complications; and,
(3) studies utilizing molecular genetic techniques to elucidate basic
mechanisms of normal and altered regulation of blood pressure.  An
important facet of the SCOR program will be a network of centers
under the oversight of a steering committee, comprised of SCOR
directors, that will ensure effective collaboration among centers.

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), Specialized Centers of Research - Molecular
Genetics of Hypertension, is related to the priority area of heart
disease and stroke.  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 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by for-profit and non-profit domestic
institutions, public and private, such as universities, colleges,
hospitals, and laboratories.  This RFA is intended to support SCOR
grants for basic and clinical investigations; therefore, applications
that include only basic or only clinical research will not be
responsive to this announcement.  In addition, clinical research
projects focused on large epidemiologic studies or large clinical
trials will be considered unresponsive to this RFA.  Awards will not
be made to foreign institutions.  However, under exceptional
circumstances, a foreign component critical to a project may be
included as a part of that project.  Women and minority investigators
are encouraged to apply.

The Principal Investigator should be an established research
scientist with the ability to ensure quality control and the
experience to administer effectively and integrate all components of
the program.  A minimum time commitment of 25 percent is expected for
this individual.  The Principal Investigator must also be the project
leader of one of the component research projects.  If, through peer
review, this project is not recommended for further consideration,
the overall SCOR application will not be considered further.  If this
project is judged by peer review to be of low scientific merit, it
will markedly reduce the overall scientific merit ranking assigned to
the entire application by the review committee.  Project leaders must
agree to commit at least 20 percent effort to each project for which
they are responsible.

MECHANISM OF SUPPORT

This RFA will use the National Heart, Lung, and Blood Institute
(NHLBI) SCOR (P50) grant to support this research program.
Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant.  All current
policies and requirements that govern the research grant programs of
the NIH will apply to grants awarded under this RFA.

Basic and Clinical Research

The overall concept of a SCOR program focuses on scientific issues
related to diseases relevant to the mission of the NHLBI.  It is
essential, therefore, that all applications include both basic and
clinical research projects.  Interactions between basic and clinical
scientists are expected to strengthen the research, enhance transfer
of fundamental research findings to the clinical setting, and
identify new research directions.  Plans for transfer of findings
from basic to clinical studies should be described.

Each SCOR grant application and award must include research involving
human patients/subjects.  Support may be provided for human
biomedical and behavioral studies of etiology, pathogenesis,
prevention and prevention strategies, diagnostic approaches, and
treatment of diseases, disorders, or conditions.  Small
population-based studies, where the research can be completed within
five years, may also be proposed.  In addition, basic research
projects must be included that relate to the clinical focus.  A SCOR
may also contain one or more core units that support the research
projects.

Length of SCOR Programs

Each NHLBI SCOR program is limited to 10 years of support.
Exceptions to this policy will be made only if a thorough evaluation
of needs and opportunities, conducted by a committee composed of
non-federal experts, determines that there are extraordinarily
important reasons to continue a specific SCOR program.

Under this policy, a given SCOR grant is awarded for a five-year
project period following an open competition.  Only one five-year
competing renewal is permitted, for a total of 10 years of support,
unless the SCOR program is recommended for extension.

The NHLBI comprehensive evaluation of the Molecular Genetics of
Hypertension SCOR program will be conducted during the second project
period according to the following timetable:

Program Announced                   FY 1994

Project Period (First Competition)  FY 1996 to FY 2000

Program Reannounced                 FY 1999

Project Period (Second Competition) FY 2001 to FY 2005

Letter to SCOR Directors            FY 2002 (midway through year 02
Regarding SCOR Evaluation Plans      of 2nd project period)

SCOR Evaluation Meeting             FY 2003 (late in year 02 of 2nd
                                    project period)

Notification of SCOR Directors      FY 2003 (midway through year 03
of NHLBI Decision                   of 2nd project period)

The NHLBI does not limit the number of SCOR applications in a given
SCOR program from one institution provided there is a different SCOR
principal investigator for each application and each application is
self-contained and independent of the other(s).  This does not
preclude cooperation, planned or possible, among participants of
SCORs after awards are made.  Scientific overlap among applications
will not be accepted.  If more than one application is envisioned
from an institution, the institution is encouraged to discuss its
plans with the NHLBI SCOR program administrator.

FUNDS AVAILABLE

Applicants may request up to $1,100,000 in direct costs, not
including indirect costs for collaborating institutions, in the first
year with a maximum increase of no more than four percent in each
additional year requested in the application.  Award of grants
pursuant to this RFA is contingent upon receipt of funds for this
purpose.  It is anticipated that approximately six SCOR grants will
be funded for a total not to exceed $9.9 million in FY 96.

Equipment is included in the budget limitation.  However, requests
for expensive special equipment that cause an application to exceed
this limit may be permitted on a case-by-case basis following staff
consultation.  Such equipment requires in-depth justification.  Final
decisions will depend on the nature of the justification and the
Institute's fiscal situation.

Consortium Arrangements

If a grant application includes research activities that involve
institutions other than the grantee institution, the program is
considered a consortium effort.  Such activities may be included in a
SCOR grant application, but it is imperative that a consortium
application be prepared so that the programmatic, fiscal, and
administrative considerations are explained fully.  The published
policy governing consortia is available in the business offices of
institutions that are eligible to receive Federal grants-in-aid.
Consult the latest published policy governing consortia before
developing the application.  If clarification of the policy is
needed, contact Ms. Jane Davis, Grants Operations Branch, NHLBI,
301-594-7436.  Applicants of SCOR grants should exercise great
diligence in preserving the interactions of the participants and the
integration of the consortium project(s) with those of the parent
institution, because synergism and cohesiveness can be diminished
when projects are located outside of the group at the parent
institution.  Indirect costs paid as part of a consortium agreement
are excluded from the limit on the amount of direct costs that can be
requested.

RESEARCH OBJECTIVES

Background

Hypertension, a complex disease that involves the interplay of
genetic and environmental factors, affects an estimated 50 million
Americans and is a major predisposing factor for myocardial
infarction, heart failure, vascular disease, stroke, and renal
failure.  Hypertension is a polygenic disease, and it has been
estimated from segregation analysis and twin studies that
approximately 45 percent of the interindividual differences in blood
pressure are accounted for by genetic differences.

The identification of the genes whose variants contribute to high
blood pressure will have far-reaching effects on our understanding of
the pathophysiology of the circulation and may suggest rational
therapeutic approaches and new preventive measures, and thereby shift
the national health focus in hypertension from post-onset therapy to
prevention.  In addition, the genetic approach may lead to the
identification of primary molecular defects that will form the basis
for mechanistic studies in humans and animals on normal blood
pressure regulation and on the pathophysiology of hypertension.  The
genetic approach may also offer crucial new insights into the
biochemical and physiological pathways that link various risk factors
to high blood pressure.

The division of the general population suffering from essential
hypertension into subgroups, defined by genotypes, may allow for the
evaluation of therapies in more homogeneous groups.  Knowledge of
these defects can provide new targets for specifically-designed
therapies.  Additionally, it may be possible to use existing
therapies in a more directed way to treat individuals with specific
genotypes.  It may not be necessary to negate the effects of all the
genes contributing to hypertension to treat the disease in an
individual.  It is likely that many genetic effects act in concert
and that neutralizing one or two of the genetic determinants
operating in an individual may be sufficient to reduce blood pressure
to a level that has less associated risk.

An understanding of the basis for genetic susceptibility to
hypertension would help identify individuals at risk for developing
the disease before the manifestation of clinical symptoms.  A major
challenge of the future in the hypertension field will be the
development and implementation of effective preventive measures.  A
better understanding of disease mechanisms should strengthen efforts
at prevention by helping to identify individuals at risk for
developing the disease before the manifestation of clinical symptoms.
Furthermore, molecular genetic studies will help investigators
characterize the prevalence of genetic variants associated with
hypertension at the population level.  Interventions based on this
information applied in advance of the rise in blood pressure have the
greatest potential for preventing the disease of hypertension.

The identification of hypertension genes provides the basis for an
understanding of the interactions between genes and environmental
factors.  It is very likely that particular environmental variables
exert effects only in the presence of certain genotypes.  Moreover,
the effects of certain environmental factors may be difficult to
detect in a genetically heterogeneous group.

Until recently, the techniques for dissecting the genetic
determinants of high blood pressure and for studying the molecular
and physiological consequences of gene variation were not available
or were not developed to an extent that would make such studies
feasible.  Several recent advances in technology and analytical
methods, together with the rapid construction of genetic and physical
maps, have substantially improved the likelihood of detecting these
genetic factors and understanding their biological implications.
These techniques have already been applied with considerable success
to single-gene disorders, such as Duchenne muscular dystrophy,
retinoblastoma, cystic fibrosis, and neurofibromatosis.  The time is
now opportune for applying these new technologies on a more
comprehensive basis to complex polygenic disorders, such as
hypertension.

Purpose of the SCOR Network

The identification of hypertension genes and a mechanistic analysis
of how these genes contribute to blood pressure regulation and to the
pathophysiology of hypertension will require the collaboration of
investigators with expertise in genetics, biostatistics, clinical
science with an emphasis on hypertension, molecular biology,
biochemistry, and physiology.  Economies of scale can be accomplished
by sharing technology, data, skills, and biological materials.
Although some research centers will have access to all necessary
resources, many of the investigators critical to the success of the
project may be located in different institutions that lack important
elements, such as the necessary human subjects.

Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the National Center for Research Resources
may wish to identify the GCRC as a resource for conducting the
proposed research.  If so, a letter of agreement from either the GCRC
program director or Principal Investigator could be included with the
application.

The choice of the word network to describe these groups emphasizes
that all of the necessary expertise, resources, and infrastructure
need not be localized at one geographical site.  The networks will
provide the cohesion and coordination that will link the best people
in several locations, covering such expenses as the exchange of
scientists, travel costs of participating groups, shipping costs of
samples and probes, data transmission and data storage costs, and the
costs of regular meetings to coordinate the activities of the network
participants.

In order to ensure the cooperative nature of this endeavor, exchange
visits of scientists among the groups will have a high priority in
the use of these funds.  In addition, key aspects of infrastructure
can also be supported, and might include immortalization of cell
lines to act as perpetual sources of DNA, the banking of DNA, the
development and maintenance of appropriate databases, and so forth.

It is important to emphasize that the approaches may differ among and
within the SCORs that will make up the network.  Regardless of the
particular strategy chosen, the applicants must carefully justify the
methodologies to be used and describe the strengths and limitations
of the proposed approaches.

Role of the Steering Committee

A meeting will be convened of all center directors at the time of
award to establish the framework for a fully functional SCOR network
by the end of the first year of funding.  An integral part of this
network will be a steering committee composed of the center
directors.  A major function of the steering committee will be to
establish and encourage well focused collaborations among network
centers.

The steering committee will be expected to meet approximately twice a
year, and center applications should include travel funds within the
budget for this purpose. Steering committee meetings will be held in
addition to the biennial one- to two-day grantee meetings in which
research accomplishments are presented by participating investigators
in each of the center grants.  The steering committee will be
responsible for overall guidance of the center network, encouraging
collaborations within and among centers, sharing resources such as
animals and samples obtained from human subjects, and ensuring a
minimum of research and budgetary duplication.

The ability to interact within a SCOR network, under the overall
guidance of a steering committee, will also be an important criterion
for evaluation.  While it is anticipated that applications for
support of research centers will encompass a complete, well balanced
multiproject research program, it is also expected that the
application will address the means by which the proposed research
program would participate in and contribute to the broader scope and
needs of a network of genetic centers.

Because it is essential that the SCOR network be dynamic and flexible
and able to respond to rapid scientific developments, applications
should include a detailed discussion of how a particular center will
be poised to take advantage of technical and methodological advances.
Although a key factor in the funding of centers will be the
scientific and technical merit as judged through the peer review
system, willingness and ability to participate actively in an ongoing
research center network will also be a key factor in selecting
applications for award.

Proposed Research

The principal research aim of this RFA is to encourage basic and
clinical research that is oriented toward mechanisms of blood
pressure control and hypertension at the genetic level.  Three broad
areas will be considered responsive to the initiative:  (1) mapping
and identification of genes responsible for high blood pressure or
its complications in humans and in experimental animal models; (2)
mechanistic studies on the biological consequences of variations in
genes linked to hypertension or its complications; and (3) studies
utilizing molecular genetic techniques to elucidate basic mechanisms
of normal and altered regulation of blood pressure.  Because this
SCOR program will involve a highly interactive network, it is not
necessary for a single center to dedicate resources to all of the
above areas.

Each SCOR will require a close association of basic bench-level and
clinical research.  At times, the clinical studies will act as the
driving force and lead the overall direction of the center network by
identifying genes that are closely associated or linked to the
hypertension or to an intermediate phenotype related to high blood
pressure in humans.

However, animal models will play at least two crucial roles.  First,
animals can be used for direct mapping of genes responsible for
experimental hypertension, as long as the comparative gene mapping
efforts will ultimately be directed toward the identification of the
corresponding genes in humans.  Second, animal models might also be
used subsequent to primary identification of human genes related to
high blood pressure as a means to clarify pathophysiological
mechanisms.  Confirmation of the pathophysiology derived from animal
studies can then be undertaken in human subjects.  Mapping and
identification of genes responsible for hypertension, whether
conducted initially in humans or in animals, will continually provide
candidate loci and hypotheses for testing in humans.

1.  Mapping and Identification of Genes

Mapping of relevant genetic loci and identification of underlying
genetic mutations responsible for high blood pressure in humans or in
experimental animal models of hypertension is an area that may be
supported through the SCOR mechanism.  Gene mapping and
identification will be complementary to other scientific efforts to
be supported by the NHLBI or through other sources.

Studies may be directed toward understanding the simultaneous
occurrence, on a genetic level, of hypertension and other diseases,
such as various forms of kidney disease, left ventricular
hypertrophy, adult-onset diabetes mellitus, and atherosclerosis.
Eventually, it may be possible to define specific genotypes that will
identify individuals at high risk for developing other diseases along
with high blood pressure.

Two principal approaches may be used to map genes that may be linked
to hypertension:  the first entails a whole genome search using
anonymous highly informative genetic markers spread throughout the
genome; the second approach involves the systematic study of
candidate genes.  Mapping can be carried out with methodologies such
as linkage in affected sib pairs, genetic linkage analysis of large
pedigrees, and association methods.  To reduce the impact of genetic
heterogeneity, the study population may be subdivided by defining
intermediate phenotypes (characteristics that have greater
heritability than the complex trait itself), or a population may be
studied that has originated from a restricted founder population or
has been isolated in some way as to limit the number of genetic
variants present.

The relative level of research activity devoted to gene mapping in
the network of centers will depend in part on the success of gene
mapping endeavors in other research programs that are not supported
by this center mechanism.  As other research programs successfully
identify genetic loci, assessments will be made by the SCOR steering
committee as to the areas that should receive scientific attention
within the SCOR network.  The center network will always be poised to
continue gene mapping and identification efforts as the
state-of-the-science requires.

2.  Mechanistic Studies on the Consequences of Genetic Variation

Investigators may select genetic variations for mechanistic studies
from a number of sources.  For instance, SCOR investigators may
choose to study allelic variations linked to high blood pressure that
have been identified and reported in the literature or that have been
identified from mapping activities within the SCOR program.  In
addition, candidate genes that are well justified in the application
may also be studied, even if they have not yet been linked to
hypertension in humans or specific animal models.

Studies may be conducted at any level of investigation, from the
molecular to the whole animal.  For example, consideration may be
given to approaches examining the implications of genetic mutations
on:  cellular function, including changes in the processing of
genetic information, synthesis or degradation of vasoactive
substances, signal transduction pathways, receptor structure and
function, and response to cytokines and growth factors; and whole
animal integrated function, using genetically altered animals, such
as congenics, transgenics, and knockouts, to clarify modifications of
organ function and implications for acute and chronic blood pressure
control.

3.  Molecular Genetic Studies on Basic Mechanisms of Normal and
Altered Blood Pressure Control

Molecular and genetic approaches that focus on the genes for other
proteins for which there is ample evidence of possible involvement in
blood pressure regulation are also excellent areas for study.
However, mechanistic studies should address the implications of
genetic alterations on normal blood pressure regulation and the
pathophysiology of hypertension.

Understanding the genetic regulation of cellular and organ responses
to elevated blood pressure is an additional area that may be
supported through the Hypertension SCORs.  Research on cellular and
organ responses to hypertension includes studies on the complications
associated with the disease, such as investigation at a genetic level
on conditions such as nephropathy or cardiac hypertrophy.  Other
topics, such as genetic determinants of vascular remodeling as a
function of high blood pressure, are also appropriate responses.

Other possible research areas are:  development and use of techniques
to introduce and express new genetic information; development and use
of approaches to abolish or modify the expression of endogenous
genes, such as homologous recombination and other gene targeting
techniques; development and application of novel approaches to alter
endogenous gene expression, such as antisense genes, ribozymes,
dominant negative mutation, or double knockouts; identification of
new genes and proteins involved in blood pressure regulation by
insertional mutagenesis; utilization of genetic ablation techniques
to unravel the complex interactions of systems comprised of multiple
cell types; and, isolation, characterization, propagation of
embryonic stem cells from rats, rabbits, and other species.

Identification of the consequences of long-term hypertension on organ
adaptation and eventually on end stage target organ disease is
another important objective of this solicitation.  It will be
particularly interesting to determine how organ adaptations to high
blood pressure are affected by predisposing genetic factors.  Some of
the sequelae to hypertension that may be studied include kidney
disease, stroke, myocardial infarction, heart failure, vascular
disease, and retinal disease.

Biennial Research Meetings

Upon initiation of the program, the NHLBI will sponsor periodic
meetings to encourage exchange of information among investigators who
participate in this program and to stimulate collaboration.
Applicants should request additional travel funds for a two-day
meeting every other year, most likely to be held in Bethesda,
Maryland.  Applicants should also include a statement in their
applications indicating their willingness to participate in these
meetings.

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS

NIH policy is that applicants for NIH clinical research grants and
cooperative agreements will be required to include women and
minorities in study populations so that research findings can be of
benefit to all persons at risk of the disease, disorder, or condition
under study.  Special emphasis should be placed on the need for
inclusion of women and minorities in studies of diseases, disorders,
and conditions that disproportionately affect them.  This policy is
intended to apply to males and females of all ages.  If women or
minorities are excluded or inadequately represented in clinical
research, particularly in proposed population-based studies, a clear
compelling rationale should be provided.

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  In addition, gender and
racial/ethnic issues should be addressed in developing a research
design and sample size appropriate for the scientific objectives of
the study.  This information should be included in the form PHS-398
in Sections 1-4 of the Research Plan AND summarized in Section 5,
Human Subjects.  Applicants are urged to assess carefully the
feasibility of including the broadest possible representation of
minority groups.  However, NIH recognizes that it may not be feasible
or appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority populations
(i.e., Native Americans [including American Indians or Alaskan
Natives], Asian/Pacific Islanders, Blacks, Hispanics).  The rationale
for studies on single minority population groups should be provided.

For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology,
prevention (and preventive strategies), diagnosis, or treatment of
diseases, disorders, or conditions, including, but not limited to,
clinical trials.

The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are not subject to
these policies.  However, every effort should be made to include
human tissues from women and racial/ethnic minorities when it is
important to apply the results of the study broadly, and this should
be addressed by applicants.  If the required information is not
contained within the application, the application will be returned.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the
selected study population is inadequate, it will be considered a
scientific weakness or deficiency in the study design and will be
reflected in assigning the priority score to the application.  NIH
funding components will not award grants or cooperative agreements
that do not comply with these policies.

LETTER OF INTENT

Prospective applicants are asked to submit, by October 1, 1994, a
letter of intent that includes a descriptive title of the proposed
research; the name, address, and telephone number of the Principal
Investigator; the identities of other key personnel and participating
institutions; and the number and title of the RFA in response to
which the application may be submitted.

Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, the information
that it contains is helpful in planning for the review of
applications.  It allows NHLBI staff to estimate the potential review
workload and to avoid conflict of interest in the review.

The letter of intent is to be sent to:

Chief, Review Branch
Division of Extramural Affairs
National Heart, Lung and Blood Institute
Westwood Building, Room 557A
Bethesda, MD  20892

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research and may be obtained from
the Office of Grants Information, Division of Research Grants,
National Institutes of Health, Westwood Building, Room 449, Bethesda,
MD 20892, telephone 301/435-0714.

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.  In addition, to identify the application as a response
to this RFA, check "YES", enter the title "Specialized Centers of
Research -- Molecular Genetics of Hypertension," and the RFA number
HL-94-006-H on Line 2a of the face page of the application.

Send or deliver a signed, typewritten original of the application,
including the checklist, and three signed photocopies, in one package
to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

Send two additional copies of the application to the Chief, Review
Branch at the address listed under LETTER OF INTENT.  It is important
to send these two copies at the same time as the original and three
copies are sent to the Division of Research Grants (DRG), otherwise
the NHLBI cannot guarantee that the application will be reviewed in
competition for this RFA.

Applications must be received by December 8, 1994.  If an application
is received after that date, it will be returned to the applicant.
DRG will not accept any application in response to this announcement
that is essentially the same as one currently pending initial review,
unless the applicant withdraws the pending application.  DRG will not
accept any application that is essentially the same as one already
reviewed.  This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications
must include an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed by National Institutes of
Health (NIH) staff for completeness and responsiveness.  Incomplete
applications or applications deemed not responsive to the RFA will be
returned to the applicant without further consideration.

Crucial to the initial scientific review will be a triage process
that will eliminate all applications that are deemed not
scientifically competitive within the goals and criteria of the RFA.

Those applications that are complete and responsive will be evaluated
for scientific and technical merit by an appropriate peer review
group convened by the NHLBI.  The second level of review will be
provided by the National Heart, Lung, Blood Advisory Council.

Factors to be considered in the evaluation of each application will
be similar to those used in review of traditional research grant
applications and, in addition, will include overall proposed
interactions among basic and clinical research projects.  Major
factors to be considered in the evaluation of applications include:

o  Scientific merit of the proposed basic and clinical research
projects including significance, importance, and appropriateness of
the theme; innovation, originality, and feasibility of the approach;
and adequacy of the experimental design.

o  Leadership, scientific stature, and commitment of the program
director; competence of the investigators to accomplish the proposed
research goals and their time commitment to the program; and the
feasibility and strength of consortium arrangements.

o  Collaborative interaction among basic and clinical research
components, the balance between them, and plans for transfer of
potential findings from basic to clinical studies.

o  Adequacy of the environment for performance of the proposed
research including clinical populations and/or specimens; laboratory
facilities; proposed instrumentation; quality controls;
administrative structure; institutional commitment; and, when needed,
data management systems.

o  Appropriateness of the budget for the proposed program.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.  Special supplemental instructions for the
preparation of grant applications for SCORs may be obtained by
contacting the Hypertension SCOR Program Administrator, as indicated
below.

Direct inquiries regarding scientific issues to:

Paul A. Velletri, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung and Blood Institute
Federal Building, Room 4C10
Bethesda, MD  20892
Telephone:  (301) 496-1857
FAX:  (301) 402-2044

Direct inquiries regarding fiscal and administrative matters to:

Ms. Jane Davis
Division of Extramural Affairs
National Heart, Lung and Blood Institute
Westwood Building, Room 4A15C
Bethesda, MD  20892
Telephone:  (301) 594-7436
FAX:  (301) 594-7492

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.837, Heart and Vascular Diseases.  Awards will be
made under the 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 requirement of Executive
Order 12372 or Health Systems Agency review.

.

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