Full Text AI-94-019

TROPICAL DISEASE RESEARCH UNITS

NIH GUIDE, Volume 23, Number 12, March 25, 1994

RFA:  AI-94-019

P.T.


Keywords: 


National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  May 24,1994
Application Receipt Date:  July 21, 1994

PURPOSE

The Division of Microbiology and Infectious Diseases (DMID) of the
National Institute of Allergy and Infectious Diseases (NIAID) invites
applications for program project grants to conduct multidisciplinary
research leading to the development and evaluation of new strategies
to prevent and control diseases caused by protozoan and helminth
parasites.  Programs will focus on one of the following areas:  (1)
development of vaccines for infection and disease; (2) discovery of
drug targets and development of new chemotherapeutic agents for
treating and preventing parasitic infections; or (3) development of
new approaches for interruption of the parasite life cycle at the
level of the invertebrate (vector) host.

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), Tropical Disease Research Units (TDRU), is
related to the priority areas of immunization and infectious
diseases.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0) or "Healthy People
2000"  (Summary Report:  Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington,
DC 20402-9325 (telephone 202-782-3238).

ELIGIBILITY REQUIREMENTS

Research grant applications may be submitted by domestic for-profit
and non-profit organizations, public and private institutions, such
as universities, colleges, hospitals, laboratories, units of State
and local governments, and eligible agencies of the Federal
government.  Foreign organizations are not eligible to apply.
Applications from minority individuals and women are encouraged.

MECHANISM OF SUPPORT

The mechanism of support will be the program project (P01) grant.
This mechanism supports broadly based multidisciplinary research
programs that have a well-defined central research focus or
objective.  An important feature of the program project is that the
interrelationships of the individual scientifically meritorious
projects will result in a greater contribution to the overall program
goals than if each project were pursued individually.  The program
project grant consists of a minimum of three interrelated individual
research projects that contribute to the program objective.  The
program project grant also can provide support for certain common
resources termed cores.  Such resources should be utilized by two or
more projects within the program project.

Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant.  The total
project period may not exceed five years.  At this time, the NIAID is
administratively limiting the duration of P01 grants to four years;
this administrative limitation may change in the future.  The
earliest anticipated award date is May 1995.

FUNDS AVAILABLE

The estimated total funds (direct and indirect costs) available for
the first year of support for this RFA will be $2.4 million.  In
fiscal year 1995, the NIAID plans to fund approximately three to four
program projects related to this RFA.  This level of support is
dependent on the receipt of a sufficient number of applications of
high scientific merit.  Applications may not request budgets in
excess of $500,000 direct costs in the first year or more than four
percent annual inflationary increases for future years.  The usual
PHS policies governing grants administration and management will
apply.  Although this program is provided for in the financial plans
of the NIAID, awards pursuant to this RFA are contingent upon the
availability of funds for this purpose.  Funding beyond the first and
subsequent years of the grant will be contingent upon satisfactory
progress during the preceding years and availability of funds.  At
this time, the NIAID has not determined whether or how this
solicitation will be continued beyond the present RFA.

RESEARCH OBJECTIVES

Background

Parasitic diseases continue to represent tremendous public health
problems, especially for people living in the tropics where parasites
are responsible for deaths and impaired growth and development of
children and debilitating, chronic diseases among adults.
Additionally, parasitic infections have been increasingly recognized
as responsible for diseases in the United States and other
industrialized countries.  Of special interest to clinicians and
public health workers in developed nations is the occurrence of
severe disease in individuals who acquired an infection congenitally
or as a result of immunosuppression.

Prevention and treatment of parasitic diseases remain problematic.
In many cases, currently available drugs exhibit either excessive
toxicity or inadequate efficacy.  Moreover, several previously useful
compounds are no longer effective due to the spread of drug resistant
parasite variants. Vaccines do not exist for any human parasitic
infection.  Environmental changes, notably those associated with land
and water management practices, have led to the emergence or
re-emergence of parasitic diseases, especially those that are
vector-borne.

Currently, the parasitology and tropical disease program in the DMID,
NIAID, consists primarily of investigator initiated research project
grants focusing on the biology (molecular and cellular biology,
immunology, and biochemistry) of the medically important protozoa and
helminths as well as the invertebrate vectors.  Biological material
in support of schistosomiasis and filariasis research is available
through repository contracts funded by the NIAID.

In addition, the NIAID also supports several special programs for
studies on parasitic and other tropical diseases.  A program to begin
in 1994 will address the development of immunotherapeutic
interventions for parasitic diseases.  The International Centers for
Tropical Disease Research (ICTDR) network coordinates all of the
NIAID's activities in the area of tropical infectious diseases.
Within the ICTDR network, studies in areas endemic for tropical
parasitic diseases are funded through its International Collaboration
in Infectious Disease Research (ICIDR) and Tropical Medicine Research
Center (TMRC) programs.  Available resources in endemic areas
supported by the ICIDR and TMRC programs may provide opportunities
for field testing of new intervention strategies as they arise.

This RFA represents a continuation of a third major component of
NIAID's ICTDR network, the Tropical Disease Research Units (TDRU)
program which was initiated in 1980 and designed to stimulate
advanced biomedical research on the five parasitic diseases
(filariasis, leishmaniasis, malaria, schistosomiasis, and
trypanosomiasis) that form the basis of the World Health
Organization's Special Programme for Research and Training in
Tropical Disease (TDR).  Since the inception of the TDRU program,
much has been learned about the biology of these and other parasites
as a result of the dramatic advances in molecular and cellular
biology and immunology.  The study of these organisms has led to the
identification and characterization of new mechanisms and structures
(e.g., lipid anchored proteins, novel forms of RNA processing, gene
rearrangements, and gene expression).  The study of parasite
interactions with the vertebrate host has also led to a greater
understanding of the role of T-cell subsets and cytokines in
pathology and protection.  Likewise, the study of the interactions
with the invertebrate host has led to a new appreciation of the role
of the vector in parasite transmission.  These recent advances in the
understanding of the basic biology of these parasites and
host-parasite interactions have created unique opportunities for
discovering and evaluating new means of controlling the mortality and
morbidity associated with parasitic infections.  The NIAID recognizes
that substantial advances have been made during this time in the
understanding of other parasitic diseases, such as amebiasis,
giardiasis and cryptosporidiosis, and that these diseases also
represent significant global public health concerns.  Therefore, for
the purposes of this recompetition, the NIAID will expand the scope
of the TDRU program to encompass all medically important human
parasitic diseases.

TDRUs will provide a resource for concerted efforts for the
development and preclinical testing of new intervention strategies
for parasitic diseases.  Components of the TDRU program will have the
opportunity to work with other members of the ICTDR network to move
promising vaccination, chemotherapeutic or vector control strategies
toward clinical or field trials.

Scope of Research

The NIAID wishes to support multidisciplinary, state of the art
biomedical research units to serve as foci for innovative research on
medically important parasites or their vectors, leading to new
intervention strategies to control the public health impact of
diseases caused by protozoa and helminths.  For the purpose of this
RFA, intervention strategies to be considered are:  (1) vaccines to
prevent infection and/or disease; (2) chemotherapeutic agents to
prevent and/or treat infection; and (3) methods to control
invertebrate vectors or interrupt the parasite's life cycle in the
vector.

The entire program project grant, consisting of three or more
projects as well as cores, must address the development of one of
these intervention strategies.  While limited to a single
intervention strategy, the program project may focus, however, on one
or more parasitic infections.

The entire program project should be designed to address the common
goal in a cohesive manner.  Thus, responsive programs would be those
in which each project provides information necessary to determine the
utility of the single intervention strategy chosen as the overall
program objective and/or develop the strategy for application.  Each
application must clearly define the mechanisms to be used to ensure
integration and exchange of information among the different projects
of the program in pursuit of this single goal.

Areas of study relevant to this program include, but are not
restricted to, the following:

o  cellular and molecular biology of medically relevant protozoa or
helminth pathogens (e.g., cell biology, genetics, genome structure,
gene expression, genetic manipulation) leading to identification of
new immunogens, chemotherapeutic targets, etc.

o  parasite virulence factors and mechanisms of pathogenesis leading
to the identification of new targets for chemotherapeutic or
immunologic intervention

o  host-pathogen interactions leading to the identification of
mechanisms of protective immunity

o  methods for improved antigen delivery/presentation or enhancement
of protective immunity leading to the design of anti-parasite
vaccines

o  parasite physiology, biochemistry and metabolism leading to a
better understanding of susceptibility and resistance to
antiparasitic agents (including structural biological studies of
essential parasite enzymes and pathways)

o  invertebrate vectors leading to identification of methods to
interrupt parasite transmission

Each application must provide an experimental plan that details the
methods that will be used to validate the utility of the chosen
approach.  The experimental plans must indicate, by use of a schedule
or time table, when the appropriate validation strategy will be
applied for evaluating the chosen approach as an intervention method.
Examples of validation strategies include:

o  use of site-directed mutagenesis, gene knockouts, testing of
specific inhibitors or antisense technology to establish the
essential nature of a drug target in programs seeking to discover and
develop new anti-parasitic agents,

o  examination of the inhibition of infection or of documented
correlates of pathology in in vitro or in vivo model systems in
programs seeking to develop vaccines or therapeutic agents,

o  examination of the inhibition of vectorial capacity for parasite
transmission in programs seeking to develop control programs targeted
at the level of the invertebrate vector.

Programs may involve collaboration among investigators at several
institutions.  For example, programs involving more developmental
aspects of the proposed studies may benefit from resources available
through collaborative arrangements with private industry.  Consortium
arrangements should follow the NIH Guide outline in "Guidelines for
Establishing and Operating Consortium Grants, January 1989."   These
are available from the individuals listed under INQUIRIES.

SPECIAL REQUIREMENTS

Institutions receiving TDRU awards are considered as Centers in the
NIAID ICTDR network and TDRU program directors are designated as
Center Directors in this network.  A further description of the
network is included as an appendix to this RFA and may be requested
from the program staff listed under INQUIRIES.  The application
should budget appropriate funds to allow the TDRU program director to
attend the annual meeting of the network, which is generally held in
Bethesda in Spring.  Attendance of other key personnel is encouraged,
but not required.

STUDY POPULATIONS

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 is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990. The new policy contains some
provisions that are substantially different from the 1990 policies.

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 9, 1994 (FR 59 11146-11151) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.

Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.

(NOTE:  When the proposed study or studies in the RFA or PA involves
a gender specific study or a single or limited number of minority
population groups, this should also be stated to inform potential
applicants and reviewers.)

LETTER OF INTENT

Prospective applicants are asked to submit, by May 24, 1994, a letter
of intent that includes a descriptive title of the overall proposed
research, the name, address, and telephone number of the Principal
Investigator, a list of the key investigators and their
institution(s), and the number and title of this RFA.  Although the
letter of intent is not required, is not binding, does not commit the
sender to submit an application, and does not enter into the review
of subsequent applications, the information that it contains allows
NIAID 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 Dr. Olivia Preble at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

Applications are to be submitted on form PHS 398 (rev. 9/91), the
standard application form for research grants.  Application kits 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.  Applicants
must adhere to the format and requirements specified in the PHS 398
application kit.  In addition, applicants for multicomponent grants
are strongly advised to read the information brochure "NIAID Program
Project Grants and Multiproject Cooperative Agreements", available
from Michael Gottlieb at the address listed under INQUIRIES.

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.  If so, a letter of agreement from either the
GCRC program director or principal investigator could be included
with the application.

For purposes of identification and processing, mark "YES" in item 2a
on the face page of the application and type in the RFA number AI-
94-019 and the title "TROPICAL DISEASE RESEARCH UNITS."  The RFA
label available in the form PHS 398 must be affixed to the bottom of
the face page of the original 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.

The signed, typewritten original of the application, including the
Checklist, and three exact single-sided copies must be sent to:

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

At the time of submission, two additional copies and all five sets of
appendices must also be sent to Dr. Olivia Preble at the address
listed under INQUIRIES.

To ensure their review, applications must be received by both the
Division of Research Grants and Dr. Olivia Preble by July 21, 1994.
Applications not received by July 21, 1994 will be considered
non-responsive and will be returned to the applicant without review.

If the application submitted in response to this RFA is substantially
similar to a grant application already submitted to the NIH for
review, but has not yet been reviewed, the applicant will be asked to
withdraw either the pending application or the new one.  Simultaneous
submission of essentially identical applications will not be allowed,
nor will essentially identical applications be reviewed by different
review committees.  Therefore, an application cannot be submitted in
response to this RFA that is essentially identical to one that has
already been 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

Review Procedures

Applications will be reviewed by DRG staff for completeness and by
NIAID staff to determine administrative and programmatic
responsiveness to this RFA.  Those judged to be incomplete or
nonresponsive will be returned to the applicant without review.
Those considered complete and responsive may be subjected to a triage
review by an NIAID peer review group to determine relative scientific
merit among the applications submitted in response to this RFA.  The
NIAID will withdraw from competition those applications judged by the
triage peer review group to be noncompetitive for award and will so
notify the applicant investigator and the institutional business
official.  Those applications judged to be competitive for award will
be reviewed further for scientific and technical merit by a Review
Committee convened by the Division of Extramural Activities, NIAID.
The second level of review will be provided by the National Advisory
Allergy and Infectious Diseases Council.

Review Criteria

The review criteria for P01 grant applications are the review
criteria for large, multicomponent, interdisciplinary program
projects as outlined in the NIAID brochure entitled "NIAID Program
Project Grants and Multiproject Cooperative Agreements."  The program
project grant application should include a justification for the
appropriateness of that granting mechanism for the proposed project.
The distinguishing features of a program project grant include:

o  A well-defined, unifying goal or problem area of research to which
each project relates and contributes, thereby producing a research
environment that allows each research effort to share the creative
strengths of others.  For the purpose of this TDRU program, the goal
will be the development of one of the intervention strategies
identified in the Scope of Research section above (i.e., chemical or
biological strategies to prevent or treat infection, disease, or
pathogen transmission via intermediate hosts).

o  A program director who possesses recognized scientific and
administrative competence.  He/she must demonstrate a substantial
commitment to the program in time and effort thereby exercising
leadership in providing overall direction and in upholding rigorous
scientific conduct.

o  Each research project must, as assessed by peer review, stand on
its own independent scientific merit, as well as complement other
projects whenever feasible.

o  The projects require the participation of established
investigators in several disciplines or investigators with special
expertise in several areas of one discipline.  All investigators must
contribute to and share the responsibilities of fulfilling the
program objective.

o  Ability of the proposed research to provide knowledge of medically
important parasitic diseases that will result in improvement in the
methods to control these diseases.  The appropriateness of the
proposed experimental plan to validate the utility of the chosen
strategy will be considered in this regard.

AWARD CRITERIA

Funding decisions will be made on the basis of scientific and
technical merit as determined by peer review, the availability of
funds, and program balance, including relevance to the control of
public health problems.  The totality of the awarded projects will
reflect the diversity of the medically relevant protozoan and
helminth parasites.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.  Requests for the brochure "NIAID Program
Project Grants and Multiproject Cooperative Agreements," as well as
inquiries regarding programmatic issues may be directed to:

Michael Gottlieb, Ph.D.
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Solar Building, Room 3A03
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-7115
FAX:  (301) 402-0804
Email:  mg35s@nih.gov

Direct inquiries regarding review issues, address the letter of
intent to, and mail two copies of the application and all five sets
of appendices to:

Olivia Preble, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C20
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-8208
FAX:  (301) 402-2638

Direct inquiries regarding fiscal matters to:

Ms. Leslie Marsden
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B29
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-7075

Schedule

Letter of Intent Receipt Date:  May 23, 1994
Application Receipt Date:       July 21, 1994
Scientific Review Date:         November 1994
Advisory Council Date:          February 1995
Earliest Date of Award:         May 1995

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance, No. 93.856 - Microbiology and Infectious 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 grants policies and
Federal Regulations 42 CFR Part 74.  This program is not subject to
the intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency 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 mental health of the american people.

.

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