Full Text PA-96-026
NIH GUIDE, Volume 25, Number 4, February 16, 1996
P.T. 34


National Institute of General Medical Sciences
The National Institute of General Medical Sciences (NIGMS) is
reannouncing its interest in receiving applications for the study of
the molecular mechanisms of action of general and local anesthetics.
This program announcement supersedes and replaces the previous
announcement by this title published in the NIH Guide for Grants and
Contracts, Vol. 17, No. 3, January 22, 1988.
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.  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).
Applications may be submitted by foreign and domestic, 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 to receive First Independent
Research Support and Transition (FIRST) Awards or program project
grants (P01).
Support of this program will be through the individual research
project grant (R01), program project grant (P01), and FIRST award
(R29).  Investigators with ongoing R01, P01 or R37 (MERIT) awards who
are expanding the scope of their work and have at least one year of
support remaining from the anticipated date of award, may wish to
consider applying for a competing supplemental award.
Individuals responding to this program announcement should cite this
program announcement by the title and number listed above.  Potential
applicants are strongly encouraged to contact the program staff
listed under INQUIRIES for guidance in the areas appropriate for
program project applications.
Since the introduction of anesthetics into clinical practice over a
century ago, the fundamental mechanisms underlying the actions of
therapeutic agents capable of ablating pain and of rendering a
patient temporarily unconscious have eluded investigators. In part,
the lack of progress in elucidating the dynamics of anesthetic action
has been due to the formidable nature of the scientific problem, as
it has been difficult to assign a direct correlation between
molecular events that are influenced by anesthetics and the
physiological effects that subsequently occur.
Recent developments in the biological sciences now offer the
opportunity to address problems fundamental to our understanding of
anesthetic action in a manner that was extremely difficult even a
decade ago.  Advances in recombinant DNA technology and molecular
biology, in biophysics and structural biology, in the neurosciences,
and in pharmacology and biochemistry now provide an opportunity for
investigators in varied fields of research to channel their expertise
and knowledge toward elucidating the actions of compounds that
exhibit anesthetic properties.  Coupled to what is perceived as an
increasing number of investigators who are interested in basic
research problems related to anesthetic action, the ability to
incorporate recent methodological and conceptual developments into
anesthesia research offers the possibility of gaining new insights
about anesthetic action that were hardly possible in the recent past.
Presumably, a wide variety of approaches and model systems could be
employed to study anesthetic action at the molecular level.  These
model systems would include but are not limited to artificial
membranes; ion channels, receptors, and other macromolecules in
reconstituted membranes; electrophysiological measurements and
biochemical determinations in isolated whole membrane systems;
studies of whole cell responses to anesthetics; and actions of
anesthetics on integrated systems such as brain slices and spinal
cord.  Additionally, experimental designs utilizing recombinant DNA
and molecular biological techniques, immunological approaches and
biophysical procedures whose aims are to elucidate structural
features of anesthetic interactions with components of biological
systems would also be of interest.
Hence, there are no limiting features to the types of approaches that
may be proposed to answer questions relevant to anesthetic action, so
long as those approaches emphasize clarification of molecular aspects
of anesthetic pharmacodynamics.  Ideally, the ultimate goal of this
research would be to develop hypotheses that might explain the
relationship between molecular actions and physiological effects of
general and local anesthetics.
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 20, 1994 (FR 59 14508-14513) 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.
Applications are to be submitted on the grant application form PHS
398 (rev. 5/95) and will be accepted at the standard application
deadlines as indicated in the application kit.  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
301/710-0267, email:  girg@drgpo.drg.nih.gov.
On the face page of the application, item 2, the "YES" box must be
checked and the title and number of this program announcement must be
typed in the space provided (i.e., Molecular Pharmacology of
Anesthetic Action, PA-96-026).
Applications for the FIRST Award (R29) must include at least three
sealed letters of reference attached to the face page of the original
application; applications submitted without the required number of
reference letters will be considered incomplete and will be returned
to the applicant without review.  The completed original application
and five legible copies must be sent or delivered to:
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)
Applications that are complete will be evaluated for scientific and
technical merit by an appropriate peer review group convened 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 applications under review, will be discussed, assigned a priority
score, and receive a second level review by the appropriate national
advisory council or board.
Review Criteria
o  scientific, technical, or medical significance and originality of
proposed research;
o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
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 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, the safety of the research
Applications will compete for available funds with all other approved
applications assigned to NIGMS. The following will be considered in
making funding decisions:
o  quality of the proposed project as determined by peer review
o  availability of funds
o  priority of research in the area of this program announcement
relative to other areas of interest to NIGMS
Inquiries are encouraged.  The opportunity to clarify any issues or
questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Alison E. Cole, Ph.D.
Division of Pharmacology, Physiology, and Biological Chemistry
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-1826
FAX:  (301) 480-2802
Email:  colea@gm1.nigms.nih.gov
Direct inquiries regarding fiscal matters to:
Ms. Toni Holland
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-5132
FAX:  (301) 480-3423
Email:  hollanda@gm1.nigms.nih.gov
This program is described in the Catalog of Federal Domestic
Assistance No. 93.859.  Awards are made under authority of the Public
Health Service Act, sections 301 and 405, and administered under PHS
grants policies and Federal Regulations 45 CFR Part 74.  This program
is not subject to the intergovernmental review requirements of
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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