Full Text PA-96-068
 
INNOVATIVE DRUG DISCOVERY RESEARCH IN AIDS OPPORTUNISTIC INFECTIONS
 
NIH Guide, Volume 25, Number 26, August 2, 1996
 
PA NUMBER:  PA-96-068
 
P.T. 34

Keywords: 
  AIDS 
  Drug Design 
  Pathophysiology 
  Infectious Diseases/Agents 

 
National Institute of Allergy and Infectious Diseases
 
Application Receipt Dates:  January 2, May 1, September 1
 
PURPOSE
 
The National Institute of Allergy and Infectious Diseases gives
special consideration for funding to scientifically meritorious
applications in response to Program Announcements.  Program
Announcements (PA) identify areas of ongoing research emphasis for
the NIAID.
 
The purpose of this PA is to seek research grant applications aimed
at novel approaches to discovery and preclinical development of
therapeutic agents and strategies against opportunistic infections
(OIs) in people with AIDS.  The intent of this Program Announcement
is to encourage investigator-initiated grant applications that
involve creative and original preclinical research that emphasizes
under-exploited facets of the basic biology, biochemistry, and
pathophysiology of the opportunistic pathogens necessary to propel
advances in improved therapies.  No clinical trials will be supported
under this PA.  Another Program Announcement, "Collaborations for
Advanced Strategies in Opportunistic Infections," soliciting research
projects that encompass laboratory research linked to
proof-of-concept clinical studies will be announced at a later date.
 
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,
Innovative Drug Discovery Research for Opportunistic Infections
Associated with AIDS, is related to the priority area of human HIV
infection.  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 REQUIREMENTS
 
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.
Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as Principal Investigators.
Foreign institutions are not eligible for First Independent Research
Support and Transition (FIRST) (R29) awards.
 
MECHANISM OF SUPPORT
 
Traditional research project grant (R01), FIRST award (R29), small
research (R03) grant, and Interactive Research Project Grants (IRPG),
awards may be submitted in response to this PA.  Applications for R01
grants may request up to five years of support.  Applications for R29
grants must request five years of support and are limited to $350,000
in direct costs over the entire project period.
 
The NIAID uses R03 grants to support small highly innovative or pilot
projects.  Applicants for R03 grants may request up to $50,000
(direct costs) per year for a period not to exceed three years.
Funds and time requested should be appropriate for the research
proposed.  Applicants for R03 grants must follow the special
application guidelines and Terms and Conditions of Award for NIAID
SMALL RESEARCH GRANTS, which appeared in the NIH Guide for Grants and
Contracts, Vol. 25, No. 9, March 22, 1996.
 
If an IRPG is proposed, it must consist of a minimum of two
independent applications (see PA-96-001, NIH Guide for Grants and
Contracts, Vol. 24, No. 35, October 6, 1995).  An IRPG may consist of
a combination of R01s and R29s or R01s only, but may not consist
solely of R29 applications.  An IRPG may also contain shared
interactive resources (Cores), which must serve at least two of the
research projects in order to facilitate achievement of the Group's
common research goals. Collaborative arrangements involving more than
one institution are especially encouraged, including participation of
the pharmaceutical industry where appropriate.
 
RESEARCH OBJECTIVES
 
Background
 
The principal causes of morbidity and mortality in AIDS are
opportunistic infections (OIs).  Although HIV is the primary cause of
the progressive immunological deterioration seen in AIDS, the OIs
account for the vast majority of all AIDS-related deaths as well as
diminishing quality of life.  Individuals infected with HIV are
susceptible to a range of viral, bacterial, protozoal, and fungal
infections.  The pathologic consequences associated with OIs in AIDS
are debilitating oral lesions, retinitis (cytomegalovirus),
progressive multifocal leukoencephalopathy (JC virus),, disseminated
nontuberculosis mycobacterial disease (M. avium), pulmonary disease
(Pneumocystis carinii), protracted diarrhea (Cryptosporidium parvum,
Enterocytozoon bieneusi), and meningitis (Cryptococcus neoformans).
 
Whereas the available treatments for OIs have improved and prolonged
the lives of people living with AIDS, the management of OIs in AIDS
patients remains difficult and complicated due to toxicity and
adverse side effects of therapeutic agents, long-term drug use
leading to patient intolerance or drug resistance, frequent relapses,
drug-drug interactions, and/or lack of standard treatments for newly
emerging OIs (e.g., JC virus, C. parvum, E. bieneusi).  New ideas and
novel approaches are urgently needed to overcome the lack of
therapeutic options available to people with AIDS-associated OIs.
 
Research Objectives and Experimental Approaches
 
The principal objective of this PA is to stimulate drug discovery
through original and innovative research focused on key metabolic and
pathophysiologic features between pathogen and host that will lead to
the discovery and development of safe, better tolerated and effective
new therapies for AIDS-associated OIs.  Equally important is the need
for rapid, non-invasive detection methods for early and specific
diagnosis and for evaluation of responses to therapy.
 
Research responsive to this PA includes studies to identify therapies
and evaluation strategies for the following infectious agents:  human
cytomegalovirus (HCMV), JC virus, Mycobacterium avium, Pneumocystis
carinii, Cryptosporidium parvum, the Microsporida, and Cryptococcus
neoformans.
 
Areas of study on these organisms include, but are not restricted to,
the following:
 
o  discovery of efficacious new antibiotics for treatment and
prevention of AIDS-associated disease;
 
o  basic cellular and molecular biology of the pathogens (virulence
factors, genome structure, and gene expression) leading to
identification of potential new chemo-or immuno-therapeutic targets;
 
o  pathogen physiology, biochemistry and metabolism leading to a
better understanding of drug susceptibility and resistance;
 
o  development of improved in vitro (cell culture) and in vivo
(animal model) systems for drug evaluations;
 
o  identification and evaluation of promising new drugs from natural
products and synthetic chemical compounds, and elucidation of their
mechanism of action;
 
o  early development and preclinical validation/standardization of
rapid, non-invasive diagnostic methods for the specific and
quantifiable detection of the infectious organism and for monitoring
response to therapy;
 
o  development of improved delivery systems for therapeutic agents.
 
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 28, 1994 (FR 59 14508-14513) and printed 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.
 
APPLICATION PROCEDURES
 
Applications are to be submitted on the grant application form PHS
398 (rev. 5/95).  Applications kits are available at most
institutional offices of sponsored research and may be obtained from
the Grants Information Office, Office of Extramural Outreach and
Information Resources, National Institutes of Health, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714,
email:  ASKNIH@odrockm1.od.nih.gov.
 
Specific guidelines for R03 applications are provided in the notice,
"NIAID Small Research Grants," NIH Guide, Vol. 25, No. 9, March 22,
1996; which is available from program staff listed under INQUIRIES.
Specific guidelines for IRPG applications are provided in PA-96-001,
NIH Guide, Vol. 24, No. 25, October 6, 1995.  Specific guidelines for
FIRST (R29) awards are provided in "First Award Guidelines (rev.
6/96).
 
Applications for FIRST (R29) awards must include at least three
sealed letters of reference attached to the face page of the original
application.  FIRST (R29) applications submitted without the required
number of reference letters will be considered incomplete and will be
returned without review.
 
Applications must be identified by checking "YES" on line 2 of the
PHS face page, and the number and title of this program announcement
must be typed in.
 
Submit a signed, typewritten original of the application, including
the Checklist, and five signed, exact photocopies in one package to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, SUITE 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)
 
R03 applicants should submit an original typewritten application and
three exact signed copies to the Division of Research Grants at the
above address, and two copies to:
 
Stanley Oaks, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C06
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-7042
FAX:  (301) 402-2638
Email:  stanley_oaks@nih.gov
 
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.
 
The Small Business Innovation Research Program (SBIR) and the Small
Business Technology Transfer Research Program (STTR) also solicit
applications in this research area.  SBIR and STTR solicitation
packages are available from:
 
MTL, Inc.
13687 Baltimore Avenue
Laurel, MD  20707-5096
Telephone:  (301) 206-9385
FAX:  (301) 206-9722
Email:  a2y@cu.nih.gov
 
The National Heart, Lung, and Blood Institute (NHLBI) and the
National Institute of Dental Research (NIDR) also have interests in
the basic biology, biochemistry, and pathophysiology of opportunistic
pathogens; in particular, how these organisms interact with host lung
cells and affect the respiratory system (NHLBI), or how they interact
with tissues and defense mechanisms of the oral cavity (NIDR).
Therefore, applications that are of mutual interest are likely to be
given a secondary assignment to NHLBI or NIDR in accordance with the
NIH referral guidelines.
 
REVIEW CONSIDERATIONS
 
R03 APPLICANTS ONLY: Review considerations and procedures are
contained in the NIAID SMALL RESEARCH GRANTS notice which appeared in
the NIH Guide for Grants and Contracts, Vol. 25, No. 9, March 22,
1996.
 
Applications will be assigned on the basis of established PHS
referral guidelines.  Program staff will be responsible for
determining whether an application is responsive to the goals of the
PA.  Applications will be reviewed for scientific and technical merit
in accordance with the standard NIH peer review procedures.
 
As part of the initial merit review, all applications may 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
 
o  scientific, technical, or medical significance and originality of
the proposed research;
 
o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
 
o  interactive nature of the component and overall program of the
IRPG (where applicable);
 
o  qualifications and research experience of the Principal
Investigator and staff, particularly but not exclusively, in the area
of the proposed research;
 
o  availability of the resources necessary to perform the research;
 
o  appropriateness of the proposed budget and duration in relation to
the proposed research;
 
o  adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
 
Plans for the recruitment and retention of subjects will also be
evaluated.
 
The initial review group will also examine 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, availability of funds.
 
INQUIRIES
 
Written and telephone inquiries are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
 
Direct inquiries regarding programmatic (eligibility, responsiveness,
and choice of funding mechanism) issues to:
 
Chris Lambros, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 2C40, MSC 7620
Bethesda, MD  20892-7620
Telephone:  (301) 402-2304
FAX:  (301) 402-3171
Email:  chris_lambros@nih.gov
 
R03 APPLICANTS ONLY: Direct inquiries regarding review issues and
special instructions for application preparation to Dr. Stanley Oaks
at the address listed under APPLICATION PROCEDURES.
 
Direct inquiries regarding fiscal and administrative matters to:
 
Ms. Jane W. Unsworth
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4B25, MSC 7610
Bethesda, MD  20892-7610
Telephone:  (301) 402-6824
FAX:  (301) 480-3780
Email:  jane_unsworth@nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalogue of Federal Domestic
Assistance No. 93.856. Awards are made under authorization of the
Public Health Service Act, Title IV, Part A (Public Law 78-410, as
amended by Public Law 99-158, 42 USC 241 and 285) and 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 the Executive Order 12372 or Health Systems
Agency review.
 
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.
 
.

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