AIDS Program Announcement

Irene Anne Eckstrand IAE at CU.NIH.GOV
Thu Dec 2 10:47:21 EST 1993


NIH GUIDE:  Volume nn, Number nn, November 19, 1993.

PA NUMBER:  TPA-94-003


National Institute of General Medical Sciences
National Institute of Diabetes and Digestive and Kidney
National Institute of Allergy and Infectious Diseases


The purpose of this program announcement is to encourage
research in areas fundamental to the development of
treatments for AIDS and associated opportunistic infections.


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, (Title of PA), is related
to the priority area of HIV infection.  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 202-783-3238).


Applications may be submitted by foreign (except for FIRST
Award and program project grants) and domestic, for-profit
and non-profit organizations, public and private, such as
universities, colleges, hospitals, laboratories, units of
State or local governments, and eligible agencies of the
Federal government.  Applications from minority individuals
and women are encouraged.


Support of this program will be through the individual
research project grant (R01), the FIRST Award (R29), and the
program project grant (P01) mechanisms as well as through
competing supplemental awards to currently active R01, P01
or Method to Extend Research in Time (MERIT) awards (R37).
Investigators holding active R01, R37, or P01 grants to
study fundamental processes associated with interaction of
proteins with ligands, bioavailability of drugs,
crystallization of proteins, macromolecular engineering, or
evolutionary adaptation, with at least one year of support
remaining at the time of the anticipated award, or
individuals desiring to apply for support under the R01 or
R29 mechanisms, are specifically encouraged to apply for
grants citing this program announcement.


Despite all that is known about fundamental biological
processes, particularly at the molecular level, and the
application of this knowledge to understanding the structure
and replication of HIV, there are still fundamental gaps in
our understanding of basic biology that must be filled
before a rational approach to the treatment of AIDS and
associated secondary infections can be accomplished.  These
gaps include:

o   A basic understanding of the factors that govern the
interaction of proteins with ligands--especially with
respect to the flexibility of both the binding site of the
protein and binding ligand.  Such an understanding is
essential for the de novo design of drugs to inhibit
specific proteins necessary for the HIV life cycle and
antibiotics to treat opportunistic infections.

o   A basic understanding of the factors that govern the
availability of a drug at its site of action.  Potential new
drug candidates frequently fail due to poor bioavailability,
i.e., the compounds show great receptor affinity, but fail
to get to their targets in sufficient quantity.  Recently,
efforts to develop HIV protease inhibitors as new drugs to
treat AIDS have foundered because of a failure to achieve
adequate intracellular drug concentrations.  The reasons why
these new drug candidates fail is not well understood, and
thus, cannot be accounted for in the design stage.

o   A basic understanding of the principles that underlie
the crystallization of proteins--especially membrane and/or
glycosylated proteins.  The inability to routinely
crystallize a given protein is a serious roadblock in the
determination of the three-dimensional structure of, for
example, the envelope protein of HIV, and other proteins
necessary for the HIV life cycle or proteins important in
the life cycle of bacteria that cause opportunistic
infections.  The determination of the structures of these
proteins at high resolution is an essential first step in
the design of drugs to inhibit the processes for which these
proteins are essential.

o   A basic understanding of the principles of
macromolecular engineering.  A promising approach in the
treatment of AIDS is to alter genetically AIDS infected
lymphocytes so that they produce proteins or nucleic acids
that inhibit either the production or escape of the AIDS
virus, misdirect specific components of AIDS virus, or are
toxic to infected cells.  A significant limitation in this
approach is the inability to engineer reliably specific
functionality into an existing protein or nucleic acid
scaffold or, at a more basic level, to design a protein or
nucleic acid de novo to perform a specific function.

o   An understanding of basic evolutionary processes by
which organisms adapt to complex environments.  The rapid
evolution of the AIDS virus, even within a single host, is a
major obstacle to vaccine and drug development and underlies
the phenomenon of multiple drug resistance.  Knowledge about
the general features which govern adaptation and evolution
is an essential step to understanding the relationship
between viral diversity and the course of infection, and the
evolution of multiple drug resistance.  These factors which
must be considered in developing vaccines and designing
drugs to make them effective.

The purpose of this announcement is to solicit proposals
that address one or more of these key issues in ways that
not only take advantage of an investigator's existing
expertise in these areas but also encourages the
investigator to recognize the implications of his or her
research to AIDS.  The expectation is that the investigator
will remain focused on the central question of AIDS during
the course of the project.

For investigators already funded by NIGMS, NIDDK or NIAID
for basic research in these areas, a competitive supplement
to provide key links to AIDS is encouraged.  In addition to
the information described in the application kit (PHS 398)
required for a supplemental application, the request should
detail how the requested funds will enable the investigator
to enhance significantly the applicability of the research
project to AIDS.


Applications for regular and supplemental awards for regular
research (R01), FIRST, and MERIT grants must be submitted on
the grant application form PHS 398 (rev. 9/91) and will be
accepted at the receipt dates for applications for AIDS-
related research: January 2, May 1, and September 1.
Applications for regular and supplemental awards for program
project grants (P01) have receipt dates of February 1, June
1, and October 1.  Application kits are available at most
institutional offices of sponsored research and may be
obtained from:

The Office of Grants Inquiries
Division of Research Grants
National Institutes of Health
Westwood Building, Room 449
Bethesda, MD 20892
Telephone: (301) 594-7248.

On the first (face) page, item 2a, of the application, the
word "yes" must be checked and the title and number of the
announcement typed in the space provided:  "Basic Research
in Support of Treatments for AIDS, PA-94-003".

The completed original application and five legible copies
must be sent or delivered to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
5333 Westbard Avenue
Bethesda, MD  20892**

FIRST (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.


Applications will be assigned to a funding component
(Institute or Center) and an Initial Review Group (IRG) on
the basis of established Public Health Service referral
guidelines.  The IRGs will review applications for
scientific and technical merit in accordance with standard
NIH peer review procedures.  Following the IRG review, the
applications will receive a second-level review by the
appropriate national advisory council.


Applications will compete for available funds with all other
approved applications.  The following will be considered
making funding decisions:

o  Quality of the proposed project as determined by peer

o  Availability of funds

o  The implications of the project for AIDS and an
intellectual environment that focuses on AIDS research

o  Program balance among research areas of the announcement


Written and telephone inquiries are encouraged.  The
opportunity to clarify any issues or questions from
potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

James Cassatt, Ph.D.
Director, Biophysics and Physiological Sciences Program
National Institute of General Medical Sciences
Westwood Building, Room 907
Bethesda, MD  20892
Telephone:  (301) 594-7800
FAX:  (301) 594-7700

Carl W. Dieffenbach, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
Solar Building, Room 2C05
Bethesda, MD  20892
Telephone:  (301) 496-8199
FAX:  (301) 402-3211

Judith Fradkin, M.D.
Endocrine and Metabolic Diseases Program Branch
National Institute of Diabetes and Digestive and Kidney
Westwood Building, Room 621
Bethesda, MD  20892
Telephone:  (301) 594-7567
FAX:  (301) 594-9011

Direct inquiries regarding fiscal matters to:

Ms. Carol Tippery
Grants Management Officer
National Institute of General Medical Sciences
Westwood Building, Room 9A03
Bethesda, MD  20892
Telephone:  (301) 594-7813

Ms. Donna A. Huggins
Grants Management Specialist
National Institute of Diabetes and Digestive and Kidney
Westwood Building, Room 649
Bethesda, MD  20892
Telephone:  (301) 594-7543

Ms. Carol B. Alderson
Grants Management Specialist
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B27
Bethesda, MD  20892
Telephone:  (301) 496-7075


This program is described in the Catalog of Federal Domestic
Assistance Nos. 93.821, 93.859, 93.862, and 93.863.  Awards
are authorized by sections 301 and 405 of the Public Health
Service Act, as amended, and administered under PHS grants
policies and Federal Regulations 45 CFR Part 74 and 45 CFR
Part 92.  This program is not subject to the
intergovernmental review requirements of Executive Order
12372 or Health Systems Agency review.

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