Full Text DC-96-005
 
MOLECULAR AND CELLULAR PATHOLOGY OF THE HUMAN AUDITORY AND VESTIBULAR
SYSTEMS
 
NIH GUIDE, Volume 25, Number 19, June 14, 1996
 
RFA:  DC-96-005
 
P.T. 34

Keywords: 
  Pathogenesis 
  Gene Cloning 
  Biology, Cellular 
  Biology, Molecular 
  Molecular Genetics 

 
National Institute on Deafness and Other Communication Disorders
 
Letter of Intent Receipt Date:  September 17, 1996
Application Receipt Date:  October 17, 1996
 
PURPOSE
 
The National Institute on Deafness and Other Communication Disorders
(NIDCD) of the National Institutes of Health (NIH) invites grant
applications to support cellular biologic, molecular biologic, and
molecular genetic studies of newly acquired and archival human
temporal bones and associated brain tissues of individuals who had
well-documented evidence of disorders of hearing and/or balance
before death.  It is believed that studies of this kind can lead to a
better understanding of the pathogenesis and pathophysiology of
disorders of the human auditory and vestibular systems.
 
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 RFA,
Molecular and Cellular Pathology of the Human Auditory and Vestibular
Systems, is related to the priority areas of physical activity
fitness, unintentional injuries, diabetes and chronic disabling
diseases and clinical prevention services.  Potential applicants may
obtain a copy of "Healthy People 2000" (Full Report:  Stock No.
017-001-11474-0 or Summary Report:  Stock No. 017-001-11473-1)
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.
Foreign institutions are not eligible for First Independent Research
Support Transition (FIRST) (R29) awards.  Consortia arrangements are
encouraged.  Domestic applications may include international
components.  Racial/ethnic minority individuals, women and persons
with disabilities are encouraged to apply as Principal Investigators.
 
MECHANISM OF SUPPORT
 
This RFA will use the National Institutes of Health (NIH) individual
research project grant (R01) and the FIRST (R29) award.  The total
project period for an application submitted in response to this RFA
may not exceed five years.  Responsibility for the planning,
direction, and execution of the proposed project will be solely that
of the applicant.
 
This RFA is a one-time solicitation, with an anticipated award date
of August 1, 1997.  Future applications for the competing
continuation of successful responses to this RFA will compete with
all investigator-initiated applications and be reviewed according to
the customary peer review procedures.
 
Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources (NCRR) 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 should be
included with the application.
 
FUNDS AVAILABLE
 
It is expected that $750,000 will be available for the first year of
support (direct cost) for this RFA and that up to three applications
will be funded.  The level of support will be dependent upon the
scientific merit and scope of the applications and the availability
of funds.
 
RESEARCH OBJECTIVES
 
Background
 
Studies of the histochemistry, immunohistochemistry and
histopathology of the human temporal bone and associated brain
structures have provided valuable knowledge about disorders of
hearing and balance.  Techniques that enable antigen retrieval and
DNA extraction from routinely processed archival temporal bones have
been developed recently.  These technical advances provide additional
opportunity for investigating the agents of disease in the auditory
and vestibular systems at the cellular and molecular levels.
Temporal bone collections with well-documented clinical histories
have thus become invaluable sources of proteins and DNA for the study
of auditory and vestibular pathology.
 
Several reports of the successful extraction of RNA and DNA from
archival human temporal bone sections and subsequent amplification by
polymerase chain reaction (PCR) have been published.  This
methodology enables the identification of genetic mutations and viral
nucleic acid sequences in pathologic tissues.  These studies have
provided the first identification and location of varicella-zoster
virus DNA in herpes zoster oticus and of herpes simplex virus DNA in
Bell's palsy.  Recently, reverse transcription of extracted RNA
followed by PCR amplification enabled the identification of a
115-base-pair sequence of the measles virus in a series of temporal
bones with histologic evidence of otosclerosis.  This study provides
evidence for a possible role of the measles virus in the etiology of
otosclerosis.
 
In order to advance histopathologic study of the human temporal bone,
particularly in the directions that are the focus of the present RFA,
the NIDCD National Temporal Bone, Hearing and Balance Pathology
Resource Registry was established by the NIDCD in 1992 under a
contract awarded to the Massachusetts Eye and Ear Infirmary.  The
Registry serves as a national resource, cataloging the pathologic
material in all known temporal bone collections in the United States
and enabling investigators to identify and locate this material by
clinical and histopathologic diagnoses and by other data so that
further studies may be pursued.  To date, the Registry contains
information on 6,227 individuals (approximately 11,500 specimens)
held in twenty-six facilities, including all fourteen laboratories
known to be currently active in temporal bone research.  The Registry
is directly accessible to remote- site users in member laboratories
and to other researchers directing requests for data searches to the
Registry staff. Other functions and accomplishments of the Registry
are described in a journal article (Arch Otolaryngol Head Neck Surg,
1993; 119: 856-853) and in the semiannual newsletter published by the
Registry.
 
Scope
 
The characterization of specific genetic alterations, viral
infections and other etiologic agents of disease using the techniques
of cellular and molecular biology holds great promise in advancing
our understanding of auditory and vestibular disorders.  There are
emerging opportunities to apply these techniques to newly acquired
and archival temporal bone and brain tissue specimens, thus enabling
the investigator to relate the pathogenesis, pathophysiology and
staging of the disease.  This initiative seeks to foster prospective,
hypothesis-driven investigations of the pathogenesis and
pathophysiology of diseases and disorders of the auditory system
and/or the vestibular system using the techniques of cellular biology
(e.g., immunohistochemistry) and/or molecular biology (e.g.,
subtractive hybridization, in situ hybridization, PCR, reverse
transcriptase PCR, in situ PCR) in newly acquired and archival human
temporal bone and associated brain tissues.  Understanding the viral,
genetic, immune system-mediated and other bases of these diseases is
a prerequisite to the development of novel strategies for prophylaxis
and therapeutics.
 
Examples of studies utilizing newly acquired and archival human
temporal bone and associated brain tissue specimens that would be
responsive to this RFA include, but are not limited to:
 
o  application of the techniques of genome analysis, such as linkage
analysis and positional cloning, to individuals who have been studied
clinically for hereditary hearing or balance impairments;
 
o  characterization of mutations in the mitochondrial or nuclear
genome as predisposing or causal factors in auditory or vestibular
system disorders, such as presbycusis, noise- induced hearing loss
and ototoxicity;
 
o  studies of immune cells, inflammatory mediators and other
molecules in chronic infectious or immune system-mediated disorders
of the auditory or vestibular systems;
 
o  analyses of the molecular and cellular pathology associated with
idiopathic sudden sensorineural hearing loss; and
 
o  searches for viral or bacterial genomes to provide evidence for
the causal or contributory roles of these microorganisms in auditory
or vestibular disorders, such as otosclerosis and Meniere's disease.
 
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 was published in the Federal
Register of March 28, 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.
 
LETTER OF INTENT
 
Prospective applicants are asked to submit, by September 17, 1996, a
letter of intent that includes a descriptive title of the proposed
research, the name, address, and telephone number of the Principal
Investigator, the identities of other key personnel and participating
institutions, and the number and title of the RFA in response to
which the application may be submitted.
 
Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, it is helpful
in planning for the review of applications.  It allows Institute
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:
 
Acting Chief, Scientific Review Branch
National Institute on Deafness and Other Communication Disorders
Executive Plaza South, Room 400C
6120 Executive Boulevard MSC-7180
Bethesda, MD  20892-7180
Telephone:  (301) 496-8683
FAX:  (301) 402-6250
 
APPLICATION PROCEDURES
 
The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these grants.  Applications kits are available at
most institutional offices of sponsored research and may be obtained
from the 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:
ASKNIH@odrockm1.od.nih.gov; and from the program administrator listed
under INQUIRIES.  The PHS 398 form is also available electronically
on the NIH Home Page at https://grants.nih.gov/grants/phs398.
 
The RFA label available in the PHS 398 (rev. 5/95) application form
must be affixed to the bottom of the face page of the 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.  In addition, the RFA title and number must be typed on
line 2 of the face page of the application form and the YES box must
be marked.
 
Submit a signed, typewritten original of the application, including
the Checklist, and three signed photocopies, in one package to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for courier/overnight service)
 
At the time of submission, two additional copies of the application
must be sent to the Chief, Scientific Review Branch, at the address
listed under LETTER OF INTENT.
 
Applications must be received by October 17, 1996.  If an application
is received after that date, it will be returned to the applicant
without review.  The Division of Research Grants (DRG) will not
accept any application in response to this RFA that is essentially
the same as one currently pending initial review, unless the
applicant withdraws the pending application.  The DRG will not accept
any application that is essentially the same as one already 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
 
Upon receipt, applications will be reviewed for completeness by DRG
and for responsiveness by the NIDCD.  Incomplete applications will be
returned to the applicant without further consideration.  If the
application is not responsive to the RFA, NIDCD program staff may
contact the applicant to determine whether to return the application
to the applicant or submit it for review in competition with
unsolicited applications at the next review cycle.
 
Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the NIDCD in accordance with the criteria
stated below.  As part of the initial merit review, all accepted
applications will receive a written critique and may undergo a
process in which only those applications deemed to have the highest
scientific merit, generally the top half of all 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.
 
Review criteria for this RFA are in general the same as those for
traditional research grant applications:
 
o  scientific or technical merit 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 the other personnel proposed to carry out the
research;
 
o  availability of resources necessary to perform the research;
 
o  appropriateness of the proposed budget and duration in relation to
the proposed research; and
 
o  responsiveness of the application to the purpose of this RFA.
 
AWARD CRITERIA
 
The following factors will be considered in making award decisions:
 
o  Scientific and technical merit, as determined by peer review;
o  Programmatic priorities; and
o  Availability of funds.
 
INQUIRIES
 
Inquiries concerning this RFA are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
 
Direct inquiries regarding scientific and programmatic issues to:
 
Daniel A. Sklare, Ph.D.
Division of Human Communication
National Institute on Deafness and Other Communication Disorders
Executive Plaza South, Room 400C
6120 Executive Boulevard MSC 7180
Bethesda, MD  20892-7180
Telephone:  (301) 496-1804
FAX:  (301) 402-6251
Email:  daniel_sklare@nih.gov
 
Direct inquiries regarding fiscal matters to:
 
Sharon Hunt
Division of Extramural Activities
National Institute on Deafness and Other Communication Disorders
Executive Plaza South, Room 400B
6120 Executive Boulevard MSC 7180
Bethesda, MD  20892-7180
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 authorization of the
Public Health Service (PHS) 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 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.
 
.

Return to RFAs Index

Return to NIH Guide Main Index

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.