NIDCD-NSBRI PROGRAM FOR THE SUPPORT OF VESTIBULAR RESEARCH

Release Date:  June 16, 1998

PA NUMBER:  PAS-98-081

P.T.

National Institute on Deafness and Other Communication Disorders
National Space Biomedical Research Institute

Application Receipt Date:  September 28, 1998

PURPOSE

The National Institute on Deafness and Other Communication Disorders (NIDCD) of
the National Institutes of Health (NIH) and the National Space Biomedical
Research Institute (NSBRI) invite research project grant applications for the
support of ground-based research on the dynamic adaptation of central vestibular
functions.  The purpose of this initiative is to promote the application of
cellular and molecular biologic approaches and advanced systems-level approaches
to the understanding of vestibular adaptation.  This research is expected to
contribute to one or both of the following goals: 1) understand the neural basis
of the autonomic responses that accompany acute vestibular dysfunction, motion
sickness and responses to altered gravitational environments, and 2) facilitate
the development of targeted approaches for the management of balance and
vestibular disorders, motion sickness and adaptation to altered gravitational
environments.

The NSBRI was established by the National Aeronautics and Space Administration
at the Baylor College of Medicine in April 1997 as a consortium of seven
institutions for the conduct of biomedical research necessary to support human
health in the exploration and development of space.  Further information on the
mission and the research components of the NSBRI is available on the World Wide
Web at http://www.nsbri.org.

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 Program Announcement (PA), NIDCD-NSBRI
Program for the Support of Vestibular Research, is related to the priority areas
of physical activity fitness, educational and community-based programs,
unintentional injuries, occupational safety and health, diabetes and chronic
disabling diseases, clinical prevention services and human resource development. 
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.  Applications from minority individuals, women and
individuals with disabilities are encouraged.

MECHANISM OF SUPPORT

The mechanism of support shall be the individual investigator-initiated research
grant (R01) award.  Although a scored application responsive to this initiative
may be awarded by either the NIDCD or the NSBRI, individual grant awards will not
be cofunded.  Hence, the grant awards made by the NIDCD and the NSBRI will be
separate and mutually exclusive.  Upon authorization from the applicant
investigator and the applicant institution (see "SPECIAL REQUIREMENTS"), the
grant application, the summary statement and related materials will be released
to the NSBRI.  The NIDCD and the NSBRI will both employ the same criteria in the
award of applications for this program (see "AWARD CRITERIA") and confer during
this process to ensure that there is no overlap in funding.

FUNDS AVAILABLE

The NIDCD has committed up to $400,000 total costs (direct cost plus facilities
and administrative allowance (indirect cost)) to this initiative for FY 99 (Year
One).  The NSBRI has committed up to $400,000 total costs for FY 99, as well. 
It is anticipated that a total of three to six awards for up to five years each
will be made in FY 99.  Awards made by the NIDCD will be administered according
to NIH policy.

RESEARCH OBJECTIVES

Background

Changes in vestibular function play a key role in numerous clinical disorders of
balance and spatial orientation on Earth and in the spatial orientation and motor
performance of space travelers during and after flight.  However, the mechanisms
responsible for vestibular adaptive changes are not well understood.  The
cellular and subcellular properties of many neurons within the vestibular system
have been characterized anatomically and physiologically, and there is evidence
implicating the involvement of both excitatory amino acid and peptide
neurotransmitters in vestibular function.  However, there have been no
comprehensive studies of the neurochemical organization of the vestibular nuclear
complex and the central vestibular pathways, nor has there been sufficient
application of systems approaches and models to relate stimulus parameters and
behavior to vestibular adaptation .  These studies are needed in order to
understand the recovery of vestibular function following injury (vestibular
compensation) and the adaptation of the vestibular system to altered
gravitational environments, including microgravity and centrifugation.

The NIDCD signed a Memorandum of Understanding with the NSBRI on June 6, 1997 for
the joint support of ground-based research in the vestibular system relevant to
the research missions of both the NIDCD and the NSBRI.  This research will be
applicable to the health of space travelers and to vestibular disorders on Earth.

Scope

Changes in vestibular function, through modifications of the processes of
learning and adaptive plasticity, underlie both treatment approaches to
vestibular disorders and adaptation to altered gravitational environments.  These
changes take place through a combination of cellular and integrated neural
network modifications.  Very little is known about the cellular- and molecular-
level processing of signals from the vestibular and nonvestibular motion sensors
in the central vestibular pathways, about the changing roles of neural circuits
during and following adaptation, and about the integrated neural network
modifications that lead to a new adapted state.  It is now possible to identify 
specific relay neurons in vitro and to determine how their cellular properties
contribute to the processing of vestibular and visual information and how this
processing is modified by cerebellar or brain stem inhibitory mechanisms.  It is
also possible to use advanced systems approaches to model integrated neural
network responses.  Knowledge of the key cellular- and systems-level events
underlying vestibular compensation and dynamic adaptation will provide a solid
basis for the improved rehabilitation of patients with balance disorders and for
management of the sensorimotor and perceptual difficulties associated with space
travel, particularly during long-duration space missions.

The purpose of this initiative is to promote the application of cellular and
molecular biologic approaches and advanced systems-level approaches to the
understanding of adaptive functions (e.g., learning and adaptive plasticity)
within the central vestibular pathways. This will afford the opportunity to merge
and maximize the efforts of cellular and systems neuroscience. Applications
submitted in response to this PA may either encompass a continuum of approaches
from reductionistic to systems-level and integrated systems-levels, or may focus
on one level of analysis.  Applicants will define how their proposed research
will contribute to one or both of the following goals: 1) understand the neural
basis of the autonomic manifestations that accompany acute vestibular
dysfunction, motion sickness and responses to altered gravitational environments,
and 2) facilitate the development of targeted pharmacotherapeutic, physical
rehabilitative and/or behavioral approaches for the management of balance and
vestibular disorders, motion sickness and adaptation to altered gravitational
environments.

SPECIAL REQUIREMENTS

Annual Meetings

The principal investigators (PIs) supported through this initiative will meet
annually for one day with the Neurovestibular Adaptation Team of the NSBRI and
with program officials of the NSBRI and the NIDCD to review the progress and to
discuss the future plans of their research projects.  The Neurovestibular
Adaptation Team is headquartered in the Boston area at the present time.  In
addition, the PIs will participate in an annual three- to four-day NSBRI-
sponsored workshop/retreat or symposium, which will usually be held in the
Houston, TX area.  These events will facilitate communication and collaborative
interactions among the investigators supported through this initiative and the
investigators comprising the Neurovestibular Adaptation Team and the other
research teams of the NSBRI.  Budget requests for travel should reflect the costs
associated with these two annual meetings and should include a statement
indicating that this travel is a special requirement of this PA.

Letter of Authorization

In order for an application to be considered for funding by the NSBRI, the
applicant must submit a brief letter of authorization, co-signed by the Principal
Investigator and the official signing for the applicant institution, authorizing
the NIDCD to release the application, the summary statement and all related
materials to the NSBRI.  These materials will be shared with the NSBRI when
available.  Applications without such authorization will not be considered for
funding by the NSBRI.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of 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
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 in the NIH Guide for Grants and Contracts,
Volume 23, Number 11, March 18, 1994.  Investigators may obtain copies from these
sources or from the program staff or contact person listed under INQUIRIES. 
Program staff will, on request, provide additional relevant information
concerning the policy.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev.
5/95).  Application kits are available at most institutional offices of sponsored
research, Division of Extramural Outreach and Information Resources, National
Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910,
telephone 301/710-0267, FAX 301/480-0525, email:  GrantsInfo@nih.gov; and from
the NIDCD program administrator listed under INQUIRIES.  The PHS 398 form is also
available electronically on the NIH Home Page at
http://www.nih.gov/grants/phs398/phs398.html.

The PA title and number (NIDCD-NSBRI Program for the Support of Vestibular
Research, PAS-98-081) must be typed in Section 2 of the face page of the
application form and the "Yes" box must be checked.  Instructions for completing
the application are found in the PHS 398 kit.

Submit the signed, original application and five exact photocopies and five
collated sets of appendix materials, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

There is only one receipt date for this PA.  Applications must be postmarked by
the receipt date of September 28, 1998.

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

Applications will be evaluated for scientific and technical merit by an
appropriate peer review group convened by the Center for Scientific Review (CSR)
in accordance with 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 National Deafness and
Other Communication Disorders Advisory Council and the NSBRI.

Review Criteria

o  Significance:  Does this study address an important problem relevant to this
PA?  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?

o  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?

o  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?

o  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)?

o  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?

o  Appropriateness of the proposed budget and duration in relation to the
proposed research.

o  For Studies Involving Human Subjects: 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

Up to a total of six research grants will be awarded separately by NIDCD and
NSBRI in response to this PA.  The anticipated date of award is August 1, 1999. 
The following criteria will be considered by both the NIDCD and the NSBRI in
making their funding decisions:

o  Responsiveness of the proposed project to the purpose of this PA;
o  Quality of the proposed project, as determined by peer review;
o  Program priorities of the NIDCD and the NSBRI within the research purview of
this PA; and
o  Availability of funds for this initiative.

INQUIRIES

Inquiries concerning this PA are encouraged.  The opportunity to clarify any
issues and to respond to questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Daniel A. Sklare, Ph.D.
Division of Human Communication
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-C - MSC 7180
Bethesda, MD  20892-7180
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 496-1804
FAX:  (301) 402-6251
Email:  daniel_sklare@nih.gov

Ronald J. White, Ph.D.
Associate Director
National Space Biomedical Research Institute
One Baylor Plaza, NA-425
Houston, TX  77030
Telephone:  (713) 798-7412
FAX:  (713) 798-7413
Email:  rwhite@bcm.tmc.edu

Direct inquiries regarding fiscal matters to:

Sharon Hunt
Division of Extramural Activities
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-B - MSC 7180
Bethesda, MD  20892-7180
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 402-0909
FAX:  (301) 402-1758
Email:  sh79f@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.173.  Awards are made under the authority 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 grant policies and Federal Regulations at 42
CFR 52 and 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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