kristoff@GENBANK.BIO.NET (Dave Kristofferson) (04/08/90)
INVESTIGATIONS INTO THE BIOLOGY OF THE RENAL MICROVASCULATURE
PA: PA-90-02
P.T. 34; K.W. 0785095, 1002004, 1002008, 0785050, 1002019, 0765035, 0710030
National Institute of Diabetes and Digestive and Kidney Diseases
The Division of Kidney, Urologic and Hematologic Diseases (DKUHD) of the
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
announces the availability of an ongoing Program Announcement (PA) on the
above subject.
BACKGROUND
Intrarenal microcirculatory forces are responsible for formation of filtrate
at the glomerulus, reabsorption of fluid by the peritubular capillaries, and
maintenance of the hyperosmotic environment in the kidney medulla.
Accordingly, mechanisms that regulate these forces in the renal vascular beds
are of paramount importance to the kidney's homeostatic function. Acting on
the hydrodynamic force derived from the heart, the smooth muscle cells of
these microcirculatory systems respond to neural, hormonal, and intrinsic
stimuli to maintain an appropriate blood flow through each "nephrovascular"
unit and an optimal hydrostatic pressure within the glomerular capillaries.
In recent years considerable attention has been focused on the renal
microvasculature in attempts to gain insight into the function of such
difficult to explore entities such as the macula densa and the juxtaglomerular
apparatus. A growing body of evidence suggests that the renal
microvasculature is the site of the integrative regulatory mechanisms involved
in the kidney's homeostatic mechanisms. In addition, disturbances in the
microvasculature at all levels in the kidney, and particularly in the
glomerulus, appear to underlie several important renal disorders. Therefore,
it is the objective of this PA to encourage increased research activity
directed toward the elucidation of the renal microvasculature.
RESEARCH GOALS AND SCOPE
This special grant program will support both fundamental and clinical
research. An emphasis of this initiative, however, is to foster extensive
collaboration between individuals in the basic sciences, including
biochemistry, cell biology, embryology, endocrinology, genetics, molecular
biology, pathology, pharmacology, renal physiology and pathophysiology. It is
the intent of this solicitation to engage investigators with diverse research
interests but who wish to apply their technologies and expertise in
elucidating and extending the current understanding of the renal
microvasculature. To that end the following are some of the objectives of
this solicitation that are being encouraged:
o Development of model culture systems that maintain the in vivo phenotype of
the cells involved in microcirculation and filtration, i.e., epithelial and
endothelial cells from various nephron segments, mesangial cells, etc.;
o Studies to identify molecular components participating in cell-cell and
cell-matrix interactions in normal and disease states;
o Studies aimed at defining in vivo roles for specific cytokines, growth
factors and eicosanoid or other mediators in physiologic microvascular
responses and in human renal diseases and animal models of renal disease,
especially through techniques identifying in situ production, local release
and/or verifiable action of specific mediators. Also, develop in vivo methods
for the assessment of intracellular signalling events critical to vascular
control systems and elaboration of growth factors;
NIH GUIDE - Vol. 19, No. 14, April 6, 1990 - Page 13
Beyond description of mediators, additional approaches may address
consequences for the local renal microvasculature arising from over-expression
of individual mediators as might occur with transgenic animal models,
retroviral expression, or other methods.
o Studies of the roles of coagulation, fibrinolytic, complement and other
mediator systems in specific models of glomerular injury;
The above are examples only and should not be viewed as all inclusive.
MECHANISMS OF SUPPORT
Support for this program will be through the grant-in-aid and will be governed
by the current policies of grant programs of the National Institutes of Health
(NIH). New applications may be submitted for the traditional,
investigator-initiated research project grant (R01) and First Independent
Research Support and Transition (FIRST) Awards (R29). Under these mechanisms,
the applicants will plan, direct, and conduct the research programs. The
project period during which the research will be conducted should adequately
reflect the time required to accomplish the stated goals and be consistent
with the policy for grant support. Support will be provided up to five years
(renewable for subsequent periods) subject to the availability of funds and
progress achieved.
Research grant applications may be submitted by both nonprofit and
profit-making organizations and institutions, State and local governments and
their agencies, and eligible agencies of the Federal government.
APPLICATION AND REVIEW PROCEDURES
The Division of Research Grants, NIH, serves as a central point for receipt of
applications for most discretionary PHS grant programs. Applications in
response to this announcement will be assigned to an Initial Review Group
(IRG) in accordance with established PHS Referral Guidelines. The IRGs,
consisting primarily of non-Federal scientific and technical experts, will
provide the peer review for scientific merit of the proposed research,
potential significance of the research findings, adequacy of methodology,
availability of necessary facilities, and the qualifications of the research
team. A secondary review will be by an appropriate National Advisory Council
that will consider the Institute's mission, policy and program relevance to
its research needs.
Applications must be submitted using Form 398 (rev. 10/88), "Application for
Public Health Service Grant", available in the business or grants office of
most academic or research institutions, or from the Office of Grants
Inquiries, Division of Research Grants, National Institutes of Health, 5333
Westbard Avenue, Bethesda, MD 20892. In order to assure proper identification
of the application, line 2 of the application form should state "Renal
Microvasculature Program Announcement, PA-90-02" and check the "YES" box.
The first receipt date for applications will be June 1, 1990, with Initial
Review Group review in September-October 1990 and Advisory Council review
January-February 1991. The earliest requested begin-date should be April 1,
1991. Thereafter, the regular NIH receipt dates for grant applications will
pertain: October 1, February 1 and June 1 of each year.
The original and six copies of the application are to be sent to:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
Prior to submitting applications, applicants are encouraged to contact:
M. James Scherbenske, Ph.D.
Renal Physiology/Cell Biology Program Director
DKUHD/NIDDK
Westwood Building, Room 621
Bethesda, MD 20892
Telephone: (301) 496-7458
**THE MAILING ADDRESS GIVEN FOR SENDING APPLICATIONS TO THE DIVISION OF
RESEARCH GRANTS OR CONTACTING PROGRAM STAFF IN THE WESTWOOD BUILDING IS THE
CENTRAL MAILING ADDRESS FOR THE NATIONAL INSTITUTES OF HEALTH. APPLICANTS WHO
USE EXPRESS MAIL OR A COURIER SERVICE ARE ADVISED TO FOLLOW THE CARRIER'S
REQUIREMENTS FOR SHOWING A STREET ADDRESS. THE ADDRESS FOR THE WESTWOOD
BUILDING IS: 5333 Westbard Avenue
Bethesda, Maryland 20816
NIH GUIDE - Vol. 19, No. 14, April 6, 1990 - Page 14
FULL TEXT OF RFAs FOR ONLINE ACCESS
REQUEST FOR RESEARCH GRANT APPLICATIONS: RFA
NIH-HL-90-06-B
STEM CELLS FOR ENGRAFTMENT: BLOOD CELLS FOR TRANSFUSION
P.T. 34; K.W. 0750010, 0780015, 0710070, 1002008, 0760020
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Letter of Intent Receipt Date: June 22, 1990
Application Receipt Date: August 1, 1990
PURPOSE
The Division of Blood Diseases and Resources, National Heart,
Lung, and Blood Institute (NHLBI), invites grant applications for
a single competition for support of basic and applied research on
the development and utilization of in vitro culture systems for
stem cells. This research will help to gain basic insights into
the control of hematopoiesis and stem cell engraftment and to
produce stem cells and other specific cell populations that might
be useful in transplantation and transfusion therapies.
DISCIPLINES AND EXPERTISE
Among the disciplines and expertise that may be appropriate for
this program are hematology, hematopoiesis, cell culture,
transplantation biology and immunology, cell biology, and
molecular biology.
ADMINISTRATIVE BACKGROUND
The Blood Diseases and the Blood Resources Branches, of the
Division of Blood Diseases and Resources (DBDR), design and
administer a broad spectrum of basic and clinical research
programs in hematopoiesis, transfusion medicine, and bone marrow
transplantation (amongst others).
SCIENTIFIC BACKGROUND
A number of research advances have occurred over the past decade
creating realistic prospects for the establishment of in vitro
culture systems for large-scale production of various marrow cell
types. Specific advances have included the definition of
hematopoietic and lymphopoietic growth factors as well as their
purification, gene cloning and initial characterization of the
genetic control of their production (1,2). In addition, there
has been a progressive increase in the characterization of bone
marrow stem cells responding to such growth factors that have the
capacity to produce a variety of differentiated cells with some
degree of self renewal (3-5). Finally, there has been
substantial work on the establishment of long-term marrow
cultures for supporting marrow growth. In murine species,
successful cultures for both lymphoid (Whitlock-Witte) and
myeloid (Dexter) cells have been extensively studied. Human
Dexter cultures, while not optimal, have been established and
under certain conditions maintain marrow cell populations for
prolonged periods. A number of bone marrow stromal cell lines
have been evaluated from a variety of species with initial data
suggesting that some of these lines may be capable of supporting
marrow cell growth (6). Components for successful production of
marrow cells would appear to include the availability of the
appropriate growth factor mix with factors both supporting early
stem cells and channeling differentiation, the appropriate marrow
target cell population, and finally some type of supporting
matrix either cellular or extracellular in nature. At the
present time, there appears to be enough basic information in
various aspects of these research areas to proceed with the
development of in vitro systems capable of generating specific
marrow cell types over prolonged periods of time. The objective
of this Request for Applications (RFA) is to support research in
developing such systems both with regard to basic insights in
control of hematopoiesis that may emerge and the potential for
producing stem cells and other specific cell populations for
transplantation and transfusion therapies.
As previously noted, major research advances have occurred that
may permit the establishment of in vitro cell production systems.
It is now conceivable that stromal cell lines or other cell
populations in which growth factor genes have been introduced
might be able to provide both physical support and the
appropriate mix of growth factors for selected target stem cell
populations so that defined populations of cells might be
produced. Establishment of such systems would be invaluable in
defining the mechanisms of growth factor production and
hematopoietic stem cell control. It would also provide a major
model system with regard to regulation of differentiation both in
hematopoiesis and in general. This type of system would allow
for the progressive evaluation of the effects of a variety of
different growth factors in a controlled system on hematopoietic
cell proliferation and differentiation. Thus, the type of model
system would be appropriate for the study of genomic control
regions of growth factor production, of hematopoietic marrow cell
response to a variety of different growth factors over prolonged
periods of time, and of the capacity of different cell
populations for both differentiation and proliferation. It would
also provide an important model system for leukemogenesis and
lymphoma evolution. With the establishment of such systems, the
underlying etiology of various cytopenias including aplastic
anemia could also be approached in a systematic fashion.
In addition, as a longer range goal, this type of development
could provide the basis for the development of large scale in
vitro stem cell and blood cell production systems for
transplantation or transfusion therapy. There is a continuing
major need for red cell component therapy in many trauma and
surgical situations, in the treatment of a variety of diseases,
and during the course of a number of therapies, particularly for
the treatment of cancer. Platelet therapy is the mainstay of
support for aggressive cancer chemotherapy and is also used
extensively in various perioperative situations. Major problems
have existed with regard to the use of transfusion therapy
including maintaining an adequate donor base, transmission of
various infectious agents especially HIV and NANB hepatitis
virus, and sensitization which renders these products
ineffective. The ability to produce large amounts of specific
blood components in vitro would offer the possibility of
overcoming these major obstacles.
In addition, the ability to maintain hematopoietic stem cells in
culture systems would offer unique opportunities for marrow
transplant therapy. Such systems would make available stem cell
populations for use in transplant and may in part solve some of
the problems of donor availability.
OBJECTIVES AND SCOPE
The objective of this initiative is to support basic and applied
research on development and utilization of in vitro culture
systems for stem cells in order to gain insights into the control
of hematopoiesis and stem cell engraftment and to produce stem
cells and other specific cell populations that might be useful in
transplantation and transfusion therapies.
The following are examples of the type of research approaches
that would be responsive to this program:
- Utilization of alternative sources of hematopoietic stem
cells such as peripheral blood, fetal liver, and cord
blood, which could then be produced in quantity in long-
term culture with the goal of providing stem cells for
engraftment (7,8).
- Studies focused on the onset of the appearance of antigens
and methods to control immunogenicity.
- Studies of the mechanism of stem cell/progenitor cell
"homing" and methods to increase engraftment (9).
- Studies on the molecular biology of the stem cell and
methodologies for its identification, purification, and
assay.
- The insertion of hematopoietic/lymphopoietic growth factor
genes into stromal cell populations and the control of
production of such growth factors in in vitro culture
systems.
- Evaluation of different extracellular matrices for
establishing and supporting long-term stem cell cultures;
elucidation of the relationship of bone marrow stromal
cells to the endothelium.
- Evaluation of purified hematopoietic stem cells, their
antigenic characterization, their proliferative and
differentiative capacity, and their in vitro growth
characteristics.
These are only examples of the types of research projects
that would be responsive to the goals of this solicitation.
Investigators are encouraged to develop their own innovative
approaches (please see EXCLUSIONS, below).
REFERENCES
1) Clark SC, Kamen R. The human hematopoietic colony
stimulating factors. Science, 236:1229-1237, 1987.
2) Kishimoto T, Taga T, Yasukawa K, et al. Molecular
structure and immunological function of human B cell
differentiation factor (BSF-2). In: Molecular Basis of
Lymphokine Action, Edited by Webb DR, Pierce CW, Cohen
S. Humana Press, Clifton, New Jersey, pp. 123-126, 1987.
3) Lemischka IR, Raulet DH, Mulligan RC. Developmental
potential and dynamic behavior of hematopoietic stem
cells. Cell, 45:917-927, 1986.
4) Ogawa M, Pharr PN, Suda T. Stochastic nature of stem
cell functions in culture. In: Hematopoietic Stem Cell
Physiology, Edited by Cronkite E, Dainiak N, McCaffrey
R, Palek J, Quesenberry P. Alan R. Liss, Inc., New York,
pp. 11-19, 1985.
5) Spangrude GJ, Heimfeld S, Weissman IL. Purification and
characterization of mouse hematopoietic stem cells.
Science, 241:58-62, 1988.
6) Song ZX, Shadduck RK, Innes Jr DJ, Waheed A, Quesenberry
PJ. Hematopoietic factor production by a cell line
(TC-1) derived from adherent murine marrow cells. Blood,
66:273-281, 1985.
7) Harrison MR, Slotnick RN, Crombleholme TM, Golbus MS,
Tarantal AF, Zanjani ED. In-utero transplantation of
fetal liver haemopoietic stem cells in monkeys. Lancet,
2:1425-1427, 1989.
8) Gluckman E, Broxmeyer HE, Auerbach AD, et al.
Hematopoietic reconstitution in a patient with Fanconi's
anemia by means of umbilical-cord blood from an
HLA-identical sibling. N Engl J Med, 321:1174-1178,
1989.
9) Matsuoka, T, Tavassoli, M. Purification and partial
characterization of membrane-homing receptors in two
cloned murine hematopoietic progenitor cell lines. J
Biol Chem, 264:20193-20198, 1989.
EXCLUSIONS
The NHLBI is primarily interested in supporting studies in
human systems. If non-human systems are proposed, it should
be clearly indicated why such studies would not be feasible
in human systems.
MECHANISM OF SUPPORT
The support mechanism for this FIVE-year program will be the
traditional individual research grant (R01). Although
approximately $1,500,000 (for direct plus indirect costs) for
this program is included in the financial plans for fiscal year
1991, award of grants pursuant to this RFA is contingent upon
receipt of funds for this purpose. The specific number of awards
to be funded depends on the merit and scope of the applications
received and the availability of funds. Since a variety of
approaches would represent valid responses to this announcement,
it is anticipated that there will be a range of costs among
individual grants awarded. While multidisciplinary approaches
are encouraged, it is not the intent of this announcement to
solicit applications for large studies encompassing a variety of
individual subprojects, i.e., Program Project Grant application.
If collaborative arrangements through subcontracts with other
institutions are planned, consult the NHLBI Grants Operations
Branch regarding procedures by calling (301) 496-7255.
Upon initiation of the program, the Division of Blood Diseases
and Resources will sponsor periodic meetings to encourage
exchange of information among investigators who participate in
this program. In the preparation of the budget for the grant
application, applicants should request travel funds for a one-day
meeting each year, most likely to be held in Bethesda, Maryland.
Applicants should also include a statement in their applications
indicating their willingness to participate in such meetings.
Applicants are requested to furnish their own estimates of the
time required to achieve the objectives of the proposed research
project. Up to FIVE YEARS of support may be requested. At the
end of the initial award period, renewal applications may be
submitted for peer review and competition for support as part of
the regular grant program of the NIH. Although it is anticipated
that support will begin in April 1991, it should be noted that
the first year of any award made in response to an
Institute-solicited program may be for less than the 12-month
recommended period.
All current policies and requirements that govern the research
grant programs of the National Institutes of Health will apply to
grants awarded in connection with this RFA. Awards in connection
with this announcement will be made to foreign institutions only
for research of very unusual merit, need, and promise, and in
accordance with Public Health Service policy governing such
awards.
REVIEW PROCEDURES AND CRITERIA
REVIEW METHOD: All applications submitted in response to this
RFA will be reviewed for scientific and technical merit by an
initial review group, which will be convened by the Division of
Extramural Affairs, NHLBI, solely to review these applications.
Upon receipt, applications will be reviewed for their
responsiveness to the objectives of this RFA. If an application
is judged unresponsive, the applicant will be contacted and given
an opportunity to withdraw the application or to have it
considered for the regular, investigator-initiated grant program
of the NIH. If an application submitted in response to this RFA
is identical to one already submitted to the NIH for review by
the Council in the same cycle, the principal investigator will be
asked to withdraw the pending application before the new one is
accepted. Simultaneous submission of identical applications will
not be allowed.
REVIEW CRITERIA: The factors to be considered in the evaluation
of scientific merit of each application will be similar to those
used in the review of traditional research project grant
applications including the novelty, originality, and feasibility
of the approach; the training, experience, and research
competence of the investigator(s); the adequacy of the
experimental design; the suitability of the facilities; and the
appropriateness of the requested budget to the work proposed.
METHOD OF APPLYING
LETTER OF INTENT: Prospective applicants are asked to submit a
one-page letter of intent that includes a descriptive title for
the planned project, and the identification of any other
participating institutions or investigators. Such letters are
requested for the purpose of obtaining an indication of the
number of applications to be received and, therefore, the NHLBI
usually does not acknowledge their receipt. A letter of intent
is not binding, nor is it a necessary requirement for
application. This letter should be received no later than June
22, 1990 and be sent to:
Charles L. Turbyfill, Ph.D.
Review Branch, Division of Extramural Affairs
National Heart, Lung and Blood Institute
Westwood Building, Room 553
Bethesda, Maryland 20892
FAX: (301) 496-7033
FORMAT FOR APPLICATIONS: Submit applications on form PHS-398
(revised 10/88), the application form for the traditional
research project grant. This form is available in an applicant
institution's office of sponsored research. Use the conventional
format for research project grant applications and ensure that
the points identified in the section on "Review Procedures and
Criteria" in this RFA are fulfilled. To identify the application
as a response to this RFA, check "yes" on item #2 of page 1 of
the application and enter the RFA title, "STEM CELLS FOR
ENGRAFTMENT: BLOOD CELLS FOR TRANSFUSION," and the RFA number
HL-90-06-B.
THE RFA LABEL ENCLOSED WITH THE PHS-398 FORM MUST BE AFFIXED TO
THE BOTTOM OF THE FACE PAGE OF THE ORIGINAL COMPLETED
APPLICATION. FAILURE TO USE THIS LABEL COULD RESULT IN DELAYED
PROCESSING AND REVIEW OF YOUR APPLICATION.
APPLICATION PROCEDURE: Send or deliver the completed application
and four signed, complete copies of it to:
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 August 1, 1990. An
application not received by this date will be considered
ineligible.
TIMETABLE:
Letter of Intent June 22, 1990
Application Receipt Date August 1, 1990
Review by the National Heart, Lung,
and Blood Advisory Council February 14-15, 1991
Anticipated Award Date April 1, 1991
INQUIRIES: Inquiries regarding this announcement may be
directed to:
Alan S. Levine, Ph.D.
Chief, Blood Diseases Branch
Division of Blood Diseases and Resources
National Heart, Lung and Blood Institute
National Institutes of Health
Federal Building, Room 5A12
Bethesda, Maryland 20892
Telephone: (301) 496-5911
FAX : (301) 496-9940
or Milton J. Hernandez, Ph.D.
Health Scientist Administrator
Blood Resources Branch
Division of Blood Diseases and Resources
National Heart, Lung and Blood Institute
National Institutes of Health
Federal Building, Room 504
Bethesda, Maryland 20892
Telephone: (301) 496-1537
FAX : (301) 496-9940
The programs of the Division of Blood Diseases and
Resources, National Heart, Lung, and Blood Institute, are
identified in the Catalog of Federal Domestic Assistance,
number 13.839. Awards will be made under the authority of
the Public Service Act, Section 301 (42 USC 241) and
administered under PHS grant policies and Federal
regulations, most specifically 42 CFR Part 52 and 45 CFR
Part 74. This program is not subject to the
intergovernmental review requirements of Executive Order
12372 or to Health Systems Agency review.
RESEARCH ON THE MOLECULAR BASIS OF CYSTIC FIBROSIS
RFA AVAILABLE: DK-90-09
P.T. 34; K.W. 0765035, 0755030, 0790005, 1013004, 0755020
National Institute of Diabetes and Digestive and Kidney Diseases
Application Receipt Date: August 1, 1990
PURPOSE
The National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) and the Cystic Fibrosis Foundation (CFF) invite
investigator-initiated research grant applications to define and
characterize the molecular pathophysiology of cystic fibrosis
(CF) and the membrane transport processes associated with the
etiology and pathogenesis of CF.
This solicitation is intended to capitalize on the recent
identification of the CF gene, the cystic fibrosis transmembrane
regulator (CFTR) protein encoded by this gene, and the major
mutation responsible for the defective function of this protein
in CF. This program will augment the ongoing NIDDK research
program in CF by providing an opportunity for investigators to
address questions related to the etiology and pathophysiology of
CF in light of these recent findings.
Applications will be submitted to the NIH and will be reviewed
according to normal NIH peer review procedures. Applications
judged meritorious but not funded by the NIH may be submitted by
the applicant, along with the NIH-prepared summary statement, to
the Cystic Fibrosis Foundation for possible funding by the
Foundation.
BACKGROUND
CF has long been known to be the result of a defective gene,
which is inherited in an autosomal recessive manner. It is also
recognized that CF is a disease of epithelial tissue in which a
defect in chloride ion transport across epithelia may be the
basis of the biophysical and biochemical alterations and the
clinical manifestations associated with CF. Attention is now
being focused on the intracellular regulatory pathways that
couple external signals such as hormones and neurotransmitters to
ion channels, pumps and carriers. Our understanding of ion
transport in epithelia has approached the level where its
relationship to the CF defect(s) and the CF gene product can be
understood at the molecular level. It is hoped that the recent
isolation of the defective gene responsible for CF will lead to
elucidation of the underlying biochemical defect(s).
OBJECTIVES
It is the intention of the NIDDK and the CFF to stimulate
research on the CF defect(s) by support of meritorious
applications proposing:
o To study processes involved in the expression and/or over-expression
of the normal or mutant products of the CF gene.
o To study the role of the CFTR protein, or other relevant membrane
proteins, in biochemical and physiological events related to
defective ion transport in CF.
o To elucidate the mechanisms by which aberrant control of ion
transport pathways in epithelial cells leads to the pathophysiology
of CF.
o To develop appropriate model systems for studying the regulation of
defective cellular processes in CF.
o To study epithelial cell membrane associated proteins other than
CFTR, such as components of transport systems or signal transduction
systems, with relevance to understanding the mechanism of the
defective ion transport in CF.
o To apply novel biophysical approaches to structural studies of
membrane transport systems, or their components, or their crystals as
they pertain to understanding the defective ion transport in CF.
o To identify and characterize potential therapeutic agents capable of
modulating the transport defect in CF.
o To develop and characterize techniques of gene transfer into cells
specifically useful in studying and/or ultimately in correcting the
transport defect in CF.
SCOPE
o The proposed research should focus primarily on genetic and transport
defects responsible for CF. The use of epithelial cell membranes
including cultured cell membranes, reconstituted membranes, or other
types of relevant cell membranes is encouraged. Studies on normal
membranes should pertain to understanding the defects in CF.
Applications which propose general mechanistic research on epithelial
cell membranes, without demonstrating direct relevance to defects in
CF, will be considered nonresponsive.
o A broad range of biophysical methods can be proposed for structural
studies of membrane transport systems or their components. These
studies should focus on the role of the CFTR, mutant variants of the
CFTR, ion channels, other transporters, or their regulators relevant
to the molecular defects in CF.
o Studies proposing crystallographic analysis should be based on
preliminary X-ray diffraction data of diffraction quality crystals.
These could be crystals of eukaryotic transporters, prokaryotic model
systems or components thereof. Given the rarity of such crystals,
the relationship of the proposed system to the anion transporter and
the molecular defect in CF can be inferential.
MECHANISM OF SUPPORT
The National Institutes of Health (NIH) will provide support for
this program through the regular research grant (R01). The
regulations (Code of Federal Regulations, Title 42, Part 52 and,
as applicable to the state and local governments, Title 45, Part
74) and policies which govern the research grant programs of the
NIH will prevail. Those grants funded by the CFF will follow CFF
guidelines. The CFF support will be limited to three years
duration with a maximum of eight percent indirect costs. With
respect to post-award administration, the current policies and
requirements that govern the regular research grant programs of
the NIH or the CFF will prevail.
The NIDDK and the CFF each plan to support approximately five to
seven applications submitted in response to this solicitation;
however, the specific number to be funded will depend upon the
overall merit, the scope of the applications received, and
availability of funds. Although this solicitation is included in
the funding plans for Fiscal Year 1991 for NIDDK, support is
contingent upon receipt of appropriated funds for this purpose.
Scientifically meritorious applications submitted to the NIH in
response to this Request for Applications (RFA) but not funded
may be submitted by the applicant to the CFF and thus become
eligible for consideration for funding by the CFF. Applicants
will have the opportunity to submit their applications and
summary statements to the CFF for consideration for funding.
REVIEW PROCEDURES AND CRITERIA
Assignment of Applications
Upon receipt, applications will be reviewed (initially) by the
Division of Research Grants (DRG) for completeness. Incomplete
applications will be returned to the applicant without further
consideration. Applications also will be reviewed by NIDDK staff
for their responsiveness to the objectives of this RFA. If an
application is considered unresponsive, the applicant will be
contacted and given an opportunity to withdraw the application or
have it considered for the regular grant program of NIH. If an
application submitted in response to this RFA is identical to a
research grant application already submitted to the NIH for
review, the applicant will be asked to withdraw the pending
application before the new one is accepted. Simultaneous
submission of identical applications in response to this RFA and
to the regular NIH grant program will not be allowed.
The National Heart, Lung, and Blood Institute also has an
interest in supporting areas of research covered by this RFA.
Should a question of program overlap arise for a given
application, the DRG Referral Guidelines will prevail in the
institute assigment of the applications.
Review Procedures
Applications in response to this RFA will be reviewed on a
nationwide basis and in accord with the usual NIH peer review
procedures. Applications will first be reviewed for scientific
and technical merit by an Initial Review Group, which will be
convened by the Review Branch, Division of Extramural Activities,
NIDDK. This group will be composed primarily of non-federal
scientific consultants. The applications will then be reviewed
by the National Diabetes and Digestive and Kidney Disease
Advisory Council or another appropriate National Advisory
Council. If the number of applications is large compared to the
number of awards to be made, the NIH may conduct a preliminary
scientific peer review to eliminate those applications which are
clearly not competitive. The NIH will administratively withdraw
from competition those applications judged to be noncompetitive
and notify the applicant and institutional business official.
Review Criteria
Review criteria include the extent of relevance and/or
contribution of the proposed research to the overall goals and
objectives of the RFA, the novelty, originality, and feasibility
of the approach; the training, experience, and research
competence of the investigator(s); the adequacy of the
experimental design; the suitability of the facilities; and the
appropriateness of the requested budget to the work proposed.
METHODS OF APPLYING
Letter of Intent
Prospective applicants are encouraged to submit an optional
one-page letter of intent, which includes the title of the
proposed project and identification of all participating
institutions. Such letters are requested only for the purpose of
obtaining an indication of the number and scope of applications
to be received. A letter of intent is not binding, and it will
not enter into the review of the application subsequently
submitted. This letter should be received no later than June 15,
1990, and should be sent to the program representative listed
under Inquiries.
Format for Applications
Applications should be submitted on Form PHS 398 (rev. 10/88),
which is available from an applicant institution's Office of
Sponsored Research or from the NIH Division of Research Grants.
Applicants should use the conventional format for research
project grant applications and ensure that the points identified
in this announcement are fulfilled. To identify the application
as a response to this RFA, check "yes" on item two of page one of
the application and enter the title "The Molecular Basis of
Cystic Fibrosis" and the RFA Number DK-90-09.
The RFA label included in the PHS 398 application kit 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.
As in the case with regular research project grant applications,
applicants are requested to furnish their own estimates of the
time required to achieve the objectives of the proposed research
project. At the end of the initial award period, renewal
applications may be submitted for further competitive review
through the regular research grant program of the NIH.
Application Procedure:
The original and four copies of the application should be sent or
delivered to:
Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building - Room 240
Bethesda, Maryland 20892**
Two additional copies of the application must be sent under separate
cover to:
Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Westwood Building, Room 406
Bethesda, MD 20892
Timetable:
The optional letter of intent should be submitted no later than
June 15, 1990. Applications must be received by August 1, 1990.
Any applications not received by this date will be considered
ineligible for this special solicitation.
APPLICATION INITIAL COUNCIL EARLIEST
Receipt Date Review Review Funding
Aug 1, 1990 Oct/Nov Jan/Feb April 1
1990 1991 1991
Inquiries:
For further information, investigators are encouraged to contact:
Nancy Lamontagne, Ph.D.
Director, Cystic Fibrosis Program
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Westwood Building, Room 607
Bethesda, MD 20892
Telephone: (301) 496-4980
This program is described in the Catalog of Federal Domestic
Assistance No. 13.847, Diabetes, Endocrinology, and Metabolic
Diseases. Awards will be made under the authority of the Public
Health Service Act, Title III, Section 301 (Public Law 78-410, as
amended; 42 USC 241) and administered under PHS grant policies
and Federal Regulations most specifically at 42 CFR Part 52 and
CFR Part 74. This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.