Subject: NIH GUIDE - RFA AI-91-14 - V20(33) 09/06/91
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Mon, 09 Sep 91 09:11 EST

Hi Paul,
This is the fifth of 11 RFAs for 910906 NIH Guide.
Please post this one to the NIH Listserver as:
RFAAI-91-14.910906
More to follow.
    Thanks, M. G. Broaddus
 ---------------------------- Text of forwarded message -----------------------
$$XID RFA AI9114 AI-91-14 P1O1 *****************************************
 
REQUEST FOR APPLICATIONS
 
RFA:  AI-91-14
 
PROGRAM PROJECTS ON TRANSPLANTATION IMMUNOLOGY
 
P.T. 34; K.W. 0745065, 0710125, 0710065
 
National Institute of Allergy and Infectious Diseases
 
Letter of Intent Receipt Date:  October 25, 1991
Application Receipt Date:  February 11, 1992
 
BACKGROUND INFORMATION
 
The Genetics and Transplantation Branch of the Division of Allergy,
Immunology and Transplantation of the National Institute of Allergy and
Infectious Diseases (NIAID) supports fundamental studies and applied
research in immunogenetics and transplantation immunology.  Program
Projects in Transplantation Immunology are intended to stimulate
collaboration between transplant clinicians and basic immunologists to
evaluate the immune response to organ allografts, elucidate the
important cellular and molecular events of both the induction and
effector phases of the alloimmune response and to develop improved
therapeutic procedures to ensure long-term graft survival.  This Request
for Applications (RFA) is a reannouncement with modified scope of RFA
89-AI-07 published in the NIH Guide for Grants and Contracts dated
December 23, 1988, Vol. 17, No. 43.  Additional reannouncement is
possible in the future depending on programmatic needs in this area and
the availability of funds.
 
RESEARCH GOALS AND SCOPE
 
The practice of transplantation has evolved such that the technical
aspects of surgery are not limiting.  The major remaining hazards are
associated with rejection and with immunosuppressive therapy employed to
prevent or control it.  Recent major advances in the understanding of
molecular and cellular processes in immunology have been made,
including:  the identification, cloning, and sequencing of the genes
encoding the T-cell receptor, the elucidation of the three-dimensional
structure of the transplantation antigens encoded by the major
histocompatibility complex and the cloning and sequencing of MHC genes,
production of monoclonal antibodies with specificity for T lymphocyte
subpopulations, and the identification of T-cell derived cytokines and
their cell surface receptors.  These major conceptual advances should
allow further clarification of the complex regulatory mechanisms
involved in the acceptance or rejection of allografts.
 
Transplant recipients subjected to manipulation of their immune systems
by means of immunomodulation and by the graft itself constitute a unique
resource and opportunity for investigation of the human immune system
that has been subjected to deliberate disturbances.  In turn, invaluable
guidance may be provided to the clinician due to a better understanding
of the immunological events that occur during transplantation and its
treatment as well as the elucidation of the mechanisms controlling these
immunological events.
 
Applications must emphasize collaborative research between transplant
clinicians and immunologists and the application of the most up-to-date
concepts and techniques of immunology to the evaluation of the immune
system of transplant recipients in all circumstances attendant to the
transplantation.  They must emphasize new ideas and innovative
approaches and must be concerned with the acquisition of new knowledge
about the immune system and its relevance to clinical transplantation.
Although the applications must stress the clinical relevance of the
proposed studies, the inclusion of basic research and preclinical
studies involving laboratory animals is encouraged.
 
The application must describe a multidisciplinary research program that
has a well-defined central research focus or objective.  As with all
program project grants, the individual component projects must be
inter-related and all projects must contribute to the overall theme and
objective of the program.  Moreover, the application must clearly
explain how the planned multidisciplinary approach can be expected to
accomplish the stated goal more efficiently and effectively than a
series of independent, individual research grant-supported studies.
 
The objective of the research must be the characterization of the status
of the immune system, specifically the immunoregulatory balance.  This
research may include studies (1) prior to transplantation in its
"normal" state or, if the transplant is occasioned by a disturbance of
the immune state, in the causative disordered state; (2) in the course
of transplant preparation that consists of the induction of tolerance;
(3) postoperatively during maintenance immunosuppression as the graft
becomes established; (4) during rejection episodes; and/or (5) during
treatment of rejection.  Also, studies on the modulation of
immunological activity using the information obtained from the above
studies would be welcome.
 
Appropriate approaches emphasizing the induction of clinical
tolerance/antigen specific unresponsiveness leading to the long-term
survival of organ allografts must be stressed.  These might include, but
are not restricted to, investigations of:
 
o the cellular and molecular mechanisms responsible for the induction of
the immune response to organ allografts and the modification of this
response with monoclonal antibodies directed to:  specific T-cell
subsets; T-cell products (e.g., lymphokines) and cell surface receptors
(e.g., the IL-2 receptor);
 
o molecular genetic manipulation of specific lymphocyte populations for
in vivo therapeutic procedures;
 
o characterization of the regulatory interactions between lymphocyte
subpopulations;
 
o the utilization of anti-idiotypic reagents in the regulation of the
immune response to allografts.
 
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS
 
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to include
minorities and women 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 minorities and women in studies of diseases, disorders and
conditions which 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, together with a rationale for
its choice.  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 Section 2, A-D of the Research Plan AND
summarized in Section 2, E, 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 excluded.  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.
 
All applications for clinical research submitted to NIH are required to
address these policies.  NIH funding components will not award grants or
cooperative agreements that do not comply with these policies.
 
MECHANISM OF SUPPORT
 
Program project (P01) grants are awarded to an institution on behalf of
a Principal Investigator for the support of a broadly based,
multidisciplinary, long-term research program with a specific major goal
or basic theme.  A program project generally involves the organized
efforts of groups of investigators who conduct research projects related
to the overall program goal.  The grant may provide support for the
projects and for certain basic resources shared by individuals in the
program project if sharing facilitates the total research effort.  Each
project supported under a program project grant is expected to
contribute to and be directly related to the common theme of the
program.  The projects, under the direction of a project leader, must
demonstrate an essential element of unity and interdependence.
 
The application must clearly explain how the projected multidisciplinary
integrated program can be expected to accomplish the stated goal more
efficiently and effectively than could a series of independent,
individual grant-supported studies.
 
Designation of a Principal Investigator as program director must be
based upon accomplishment and experience as a scientist, the ability to
assume both the leadership of the research group and the responsibility
for scientific, professional, and administrative functions, and the
commitment of a significant amount of his/her time to the project.  Each
project in the program must have a designated project leader with a
demonstrable record of accomplishment in clinical immunology or one of
the basic science disciplines or clinical specialties relevant to the
particular subject of investigation.  However, the participation of one
junior, but independent, investigator whose project is an integral part
of the overall program and whose work would be closely related to that
of the senior scientist project leaders of the other projects is
encouraged by the NIAID.
 
Support for a competing program project in Program Projects in
Transplantation Immunology will be limited to a maximum of five years.
Competing renewals may be submitted in response to an RFA or as an
unsolicited application.  Such applicants are strongly encouraged to
contact Dr. Stephen Rose prior to submitting an application.  Funding
beyond the first and subsequent years of the grant will be contingent
upon satisfactory progress during the preceding years and availability
of funds.  In Fiscal Year 1992 the NIAID plans to award at least two
program project grants submitted in response to this RFA and, depending
on availability of funds and scientific merit, more than two.
First-year budget requests must be limited to no more than $500,000
direct costs.  Direct cost funds may be utilized to support the research
activities of scientific and professional personnel, consultation
services, equipment, supplies, travel, and publication costs.  Support
for research-related costs of patient involvement and medical care may
be authorized.  No funds will be provided for new construction;
therefore, adequate physical facilities must be available for the
primary needs of the project.  However, moderate alterations or
renovations to enhance clinical or laboratory facilities may be allowed
if they are necessary to meet objectives of the proposed program.
 
Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research Resources
may wish to identify the GCRC as a resource for conducting the proposed
research.  In such a case, a letter of agreement from either the GCRC
program director or the Principal Investigator of the GCRC must be
included with the application.
 
ELIGIBILITY
 
ONLY DOMESTIC INSTITUTIONS ARE ELIGIBLE TO APPLY.  Applications may be
submitted by any public or private, nonprofit or profit-making,
organization.
 
REVIEW PROCEDURES AND CRITERIA
 
These are outlined in the NIAID Information Brochure on Program Project
and Center Grants that contains special instructions and information for
preparing multiproject applications for program project grants, review
procedures and criteria, and other important information.  Before
proceeding, the prospective applicant should read this brochure that is
available from Dr. Mark Rohrbaugh at the address below.
 
Applications will be examined by NIAID staff to determine administrative
and programmatic responsiveness to this RFA.  Those judged to be
non-responsive will be returned to the applicant without review.
 
Those applications that are complete and responsive may be subjected to
a triage by an NIAID peer review group before the scientific review
meeting to determine their scientific merit relative to other
applications received in response to this RFA.  The NIAID will withdraw
from competition those applications judged to be non-competitive for
award and will notify the applicant and institutional business official.
 
Those applications judged by the reviewers to be competitive for award
will be further reviewed for scientific and technical merit by a review
committee convened by the Division of Extramural Activities, NIAID,
during June or July 1992.  The second level of review will be provided
by the National Advisory Allergy and Infectious Disease Council in
September 1992.  September 28, 1992 will be the earliest starting date
for successful applicants.
 
METHOD OF APPLYING
 
In addition to following the format instructions contained in the
Information Brochure for the development of a program project grant
application, include the expanded material listed below:
 
o A brief overview of the intended program project and its components;
 
o A description of laboratory and clinical facilities available for use
by the proposed project;
 
o Ongoing relevant research studies identifying existing projects and
sources of support;
 
o Past research by members of the proposed investigative group relevant
to the application;
 
o Specific information on the institution's present patient load and
projections for patient involvement in clinical investigations;
 
o The academic positions and major research interests of the program
director and his/her professional staff who will be involved in the work
of the program project;
 
o Collaborative arrangements with other laboratories and investigators
and delineation of the role and manner of anticipated participation and
interaction of the project leader(s), consultants, and collaborators;
 
o Justification for the use of the PO1 mechanism as opposed application
for individual RO1 grants.
 
The receipt date for applications will be February 11, 1992.
APPLICATIONS NOT RECEIVED AS A SINGLE PACKAGE FROM THE APPLICANT
ORGANIZATION BY FEBRUARY 11, 1992, OR THAT DO NOT CONFORM TO THE
INSTRUCTIONS CONTAINED IN FORM PHS 398 (rev. 10/88) APPLICATION KIT,
WILL BE JUDGED TO BE NON-RESPONSIVE AND WILL BE RETURNED TO THE
APPLICANT.
 
Use the research grant application form PHS 398 (rev. 10/88).  For
purposes of identification and processing, the words "PROGRAM PROJECTS
IN TRANSPLANTATION IMMUNOLOGY" and the RFA number must be typed in item
2 on the face page of the application.
 
THE RFA LABEL AVAILABLE IN THE 10/88 REVISION OF APPLICATION FORM PHS
398 MUST BE AFFIXED TO THE BOTTOM OF THE FACE PAGE.  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.
 
Application kits may be obtained from the institution's office of
sponsored research and from:
 
Office of Grants Inquiries
Division of Research Grants
National Institutes of Health
Westwood Building, Room 449
Bethesda, MD  20892
 
Submit a signed, typewritten original of the application, including the
Checklist, and four signed, exact, single-sided photocopies, in one
package to:
 
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**
 
IN ADDITION mail two exact copies of the application and six copies of
the appendices directly to Dr. Mark Rohrbaugh at the following address:
 
Mark L. Rohrbaugh, Ph.D.
Scientific Review Administrator
NIAID/PPRB
Control Data Building, Room 406-S
6003 Executive Boulevard
Bethesda, MD  20892 (20852 if using overnight delivery services)
Telephone:  (301) 496-8424
 
LETTER OF INTENT:  Prospective applicants are asked to submit by October
25, 1991, a letter of intent that includes a descriptive title of the
overall proposed research, the name of the Principal Investigator, and a
list of the names of key investigators and their institution(s).  The
letter of intent is requested in order to provide an indication of the
number and scope of applications to be reviewed so as to allow early
preparations for review.  Applicants are strongly encouraged to contact
Dr. Stephen Rose prior to preparing an application.  The letter of
intent is not binding and does not commit the sender to submit an
application, nor is it a requirement for submission of an application.
The letter of intent is to be directed to Dr. Mark Rohrbaugh at the
address given above and a copy to Dr. Stephen Rose at the address given
below.
 
In addition, it is highly recommended that the Chief of the Genetics and
Transplantation Branch be contacted in the early stages of preparation
of the application:
 
Stephen M. Rose, Ph.D.
Chief, Genetics and Transplantation Branch
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
National Institutes of Health
5333 Westbard Avenue, Room 754
Bethesda, MD  20892
Telephone:  (301) 496-5598
Telefax:  (301) 402-0175
 
INQUIRIES
 
Inquiries concerning the programmatic aspects of this RFA may be
addressed to Dr. Rose at the address given above.
 
Inquiries regarding the review of these applications are to be addressed
to Dr. Rohrbaugh at the address given above.
 
Inquiries regarding fiscal matters may be addressed to:
 
Mr. Jeffrey Carow
Chief, Immunology Grants Management Section
GMB, DEA, NIAID, NIH
Westwood Building, Room 726
Bethesda, MD  20892
Telephone:  (301) 496-7075
 
and
 
Ms. Marietta Robinson
Grants Management Specialist
GMB, DEA, NIAID, NIH
Westwood Building, Room 706
Bethesda, MD  20892
Telephone:  (301) 496-7075
 
This program is described in the Catalog of Federal Domestic Assistance
No. 93.855, Immunology, Allergic and Immunologic Diseases Research.
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 Regulation 42 CFR
Part 74.  This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency review.