Full Text PA-97-083
 
TUBERCULOSIS - BASIC  BIOLOGY, IMMUNOLOGY AND PATHOGENESIS
 
NIH GUIDE, Volume 26, Number 24, July 25, 1997
 
PA NUMBER:  PA-97-083
 
P.T.


Keywords: 

 
National Institute of Allergy and Infectious Diseases
National Heart, Lung, and Blood Institute
 
PURPOSE
 
The National Institute of Allergy and Infectious Diseases (NIAID)and
National Heart, Lung, and Blood Institute (NHLBI), National
Institutes of Health (NIH), invite applications focused on
elucidating the basic biology, immunology and pathogenesis of
mycobacteria, and host-mycobacterial interactions relevant to
increasing and consolidating our fundamental understanding of
tuberculosis.
 
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 PA,
"TUBERCULOSIS - BASIC BIOLOGY, IMMUNOLOGY AND PATHOGENESIS", is
related to the priority areas of: Immunization and Infectious Disease
and HIV Infection and AIDS.  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 202-512-1800).
 
ELIGIBILITY
 
Applications may be submitted by domestic and foreign, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Foreign institutions are not eligible for FIRST (R29).  Racial/ethnic
minority individuals, women, and persons with disabilities are
encouraged to apply as Principal Investigators.
 
MECHANISM OF SUPPORT
 
Traditional research project grant (R01) and FIRST award (R29)
applications may be submitted in response to this program
announcement.  Applications for R01 grants may request up to five
years of support; applications for R29 grants must request five years
of support.  Responsibility for the planning, direction, and
execution of the proposed research will be solely that of the
applicant.
 
RESEARCH OBJECTIVES
 
Background
 
Tuberculosis remains the leading cause of death throughout the world
due to a single infectious agent (Mycobacterium tuberculosis or
M.tb). In 1989 the U.S. Federal Government declared the goal of
eliminating tuberculosis from the United States by the year 2010,
with elimination defined as less than 0.1 cases per 100,000
population.  It set an interim goal of 3.5 cases per 100,000 by the
year 2000.  CDC recently reported that in 1995 the US experienced
22.86 cases of tuberculosis per 100,000.  Thus we remain far from
even our interim goal.  It appears evident that tuberculosis will not
be eliminated from the US and the world without a more effective
vaccine(s).  The only currently available vaccine, BCG, has shown
marked variability in its effectiveness against adult pulmonary
tuberculosis, the major burden of disease.  Furthermore, BCG is not
recommended for general use in the United States and other countries
with relatively low rates of endemic disease, because vaccination
with BCG confounds surveillance efforts.  Rational design of improved
vaccines and other intervention strategies requires a broader and
firmer base of fundamental knowledge regarding the biology of
mycobacteria and their interactions with the host.
 
Research Objectives and Scope
 
NOTE:  Three complementary Program Announcements are being issued:
"The Latent State in Tuberculosis Infection"; "Tuberculosis - Basic
Biology, Immunology and Pathogenesis"; and "Innovative Approaches to
Investigating Human Tuberculosis".
 
Applications which focus on understanding the latent state in
tuberculosis infection and/or reactivation of tuberculosis should be
submitted in response the PA "The Latent State in Tuberculosis
Infection".  Applications which focus on the use of model systems and
or mycobacterial species other than M.tb to further understanding of
any other aspect of tuberculosis should be submitted in response to
the PA "Tuberculosis - Basic Biology, Immunology and Pathogenesis";
and applications which primarily focus on use of M.tb and/or human
cells, tissues or study populations to study any aspect of human
tuberculosis, per se, other than latency/reactivation should be
submitted in response to the PA "Innovative Approaches to
Investigating Human Tuberculosis".
 
Acquiring the crucial information needed to develop improved
intervention and therapeutic strategies for tuberculosis control
requires a broad range of studies including, but not limited to: o
developing improved tools for genetic manipulation of mycobacteria
 
o  determining the molecular basis of relevant pathogen/host cell
interactions, including, but not limited to, very early events of
infection, mechanisms of phagolysosomal evasion, and identification
and isolation of virulence and invasion factors
 
o  elucidating the biology and biochemistry of mycobacterial genetic
mechanisms and the signals that modulate these processes
 
o  characterizing mycobacterial physiology at the molecular and
biochemical levels - including, but not limited to, roles of
'housekeeping' genes and their products, unique biochemical pathways,
and nutrient transport mechanisms
 
o  defining the protective immune response and immunopathogenic
mechanisms in mycobacterial infections, including the roles of
mucosal immunity and responses directed at nonprotein as well as
protein antigens
 
o  identifying and elucidating transport mechanisms for bacterial
products, including possible translocation of mycobacterial antigens
within host cells
 
o  developing methods to overcome technical challenges posed by
slow-growing mycobacteria; this could include collaborations with
bacterial physiologists experienced in molecular and biochemical
investigations of other slow-growing organisms (e.g., Archaebacteria,
Methanobacteria).
 
These studies, while relevant ultimately to improving our
understanding and knowledge of human tuberculosis, may employ model
mycobacterial strains and animal systems, as appropriate.
 
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS
 
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification are
provided that inclusion is inappropriate with respect to the health
of the subjects of the purpose of the research.  This policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43).
 
All investigators proposing research involving human subjects should
read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research", which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and the NIH
Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994.
 
Investigators may obtain copies from these sources or from the
program staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
 
APPLICATION PROCEDURES
 
Applications are to be submitted on the grant application for PHS 398
(rev. 5/95) and will be accepted on the standard application
deadlines as indicated in the application kit.
 
Application kits are available at most institutional offices of
sponsored research and may be obtained from the Office of Extramural
Outreach and Information, National Institutes of Health, 6701
Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301)
435-0714, email: asknih@odrockm1.nih.gov.
 
For purposes of identification and processing, item 2 on the face
page of the application must be marked "YES".  The PA number and the
PA title must also be typed in section 2.
 
The completed, signed original and five legible, single-sided copies
of the application and any appendices must be sent or delivered to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817-7710 (for express/courier service)
 
R29 applications must include at least three sealed letters of
reference attached to the face page of the original application.
FIRST applications submitted without the required number of reference
letters will be considered incomplete and will be returned without
review.
 
Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the Center as a resource for
conducting the proposed research.  If so, a letter of agreement from
the GCRC Program Director must be included in the application
material.
 
REVIEW CONSIDERATIONS
 
Review Procedures
 
Applications will be assigned on the basis of established PHS
referral guidelines. Upon receipt, applications will be reviewed for
completeness by the NIH Division of Research Grants.  Incomplete
applications will be returned to the applicant without further
consideration.
 
Applications will be reviewed for scientific and technical merit by
study sections of the Division of Research Grants, NIH, in accordance
with the standard NIH peer review procedures. As part of the initial
merit review, all applications will receive a written critique and
undergo a process in which only those applications deemed to have the
highest scientific merit, generally the top half of the applications
under review, will be discussed, assigned a priority score, and
receive a second level review by the appropriate national advisory
council.
 
Review Criteria
 
The five criteria to be used in the evaluation of grant applications
are listed below.
 
The goals of NIH-supported research are to advance our understanding
of biological systems, improve the control of disease, and enhance
health.  The reviewers will comment on the following aspects of the
application in their written critiques in order to judge the
likelihood that the proposed research will have a substantial impact
on the pursuit of these goals.  Each of these criteria will be
addressed and considered by the reviewers in assigning the overall
score weighting them as appropriate for each application.  Note that
the application does not need to be strong in all categories to be
judged likely to have a major scientific impact and thus deserve a
high priority score.  For example, an investigator may propose to
carry out important work that by its nature is not innovative but is
essential to move a field forward.
 
1.  Significance.  Does this study address an important problem? If
the aims of the application are achieved, how will scientific
knowledge be advanced?  What will be the effect of these studies on
the concepts or methods that drive this field?
 
2.  Approach.  Are the conceptual framework, design, methods, and
analyses adequately developed, well-integrated, and appropriate to
the aims of the project?  Does the applicant acknowledge potential
problem areas and consider alternative tactics?
 
3.  Innovation.  Does the project employ novel concepts, approaches
or method?  Are the aims original and innovative? Does the project
challenge existing paradigms or develop new methodologies or
technologies?
 
4.  Investigator.  Is the investigator appropriately trained and well
suited to carry out this work?  Is the work proposed appropriate to
the experience level of the principal investigator and other
researchers (if any)?
 
5.  Environment.  Does the scientific environment in which the work
will be done contribute to the probability of success?  Do the
proposed experiments take advantage of unique features of the
scientific environment or employ useful collaborative arrangements?
Is there evidence of institutional support?
 
The initial review group will also examine: the appropriateness of
proposed project budget and duration; the adequacy of plans to
include both genders and minorities and their subgroups as
appropriate for the scientific goals of the research and plans for
the recruitment and retention of subjects; the provisions for the
protection of human and animal subjects; and the safety of the
research environment.
 
AWARD CRITERIA
 
Applications will compete for available funds with all other
favorably recommended applications.  The following will be considered
when making funding decisions: quality of the proposed project as
determined by peer review, program balance among research areas of
the announcement, and availability of funds.
 
INQUIRIES
 
Written and telephone inquiries are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
 
Inquiries regarding programmatic issues may be directed to:
 
Ann M. Ginsberg, MD, Ph.D.
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Solar Building, Room 3B06
6003 Executive Blvd.
Bethesda, MD 20892-7630
Telephone: (301) 496-5305
Fax:       (301) 496-8030
EMAIL:     ag73i@nih.gov
 
Hannah H. Peavy, M.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
Two Rockledge Centre, Suite 10018, MSC 7952
6701 Rockledge Drive
Bethesda, Maryland 20892-7952
Telephone:  (301) 435-0222
FAX:  (301) 480-3557
E-mail: hannah_peavy@nih.gov
 
Direct inquiries regarding fiscal matters to:
 
Ms. Catherine Walker
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B32
6003 Executive Blvd.
Bethesda, MD  20892-7610
Telephone: (301)402-7146
Fax: (301)480-3780
Email: cwalker@mercury.niaid.nih.gov
 
Raymond L. Zimmerman
Grants Operations Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Two Rockledge Centre, Suite 7154, MSC 7926
6701 Rockledge Drive
Bethesda, MD 20892-79??
Telephone:  (301) 435-0171
FAX:  (301) 480-3310
E-mail: raymond_zimmerman@nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is supported under authorization of the Public Health
Service Act, Sec. 301(c), Public Law 78-410, as amended.  The
Catalogue of Federal Domestic Assistance Citations are No. 93.838.
and No. 93.856.  Awards will be administered under PHS grants
policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74.
This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems review.
 
The Public Health Service strongly encourages all grant recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  This is consistent with the PHS mission to protect and
advance the physical and
 
.

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