PA-04-118: CELL LINEAGE AND DEVELOPMENTAL STUDIES IN HEARING AND BALANCE

CELL LINEAGE AND DEVELOPMENTAL STUDIES IN HEARING AND BALANCE

RELEASE DATE: June 22, 2004

PA NUMBER: PA-04-118

December 8, 2006 - The R01 portion of this funding opportunity has been
replaced by PA-07-127, which now uses the electronic SF424 (R&R)
application for February 5, 2007 submission dates and beyond.

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date,
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using
the electronic SF424 (R&R) application. This announcement will stay active for
only the May 1, 2006 AIDS and AIDS-related application submission date for these
mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms
expires on the date indicated below. Other mechanisms relating to this announcement
will continue to be accepted using paper PHS 398 applications until the stated
expiration date below, or transition to electronic application submission.
A replacement R21 (PA-06-365) funding opportunity announcement has been issued
for the submission date of June 1, 2006 and submission dates for AIDS and
non-AIDS applications thereafter.

EXPIRATION DATE for R21 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R21 AIDS and AIDS-Related Applications: May 2, 2006
Expiration Date for R01 Non-AIDS Applications: November 2, 2006 Expiration Date for R01 AIDS and AIDS-Related Applications: January 3, 2007

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
(http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:
National Institute on Deafness and Other Communication Disorders (NIDCD)
(http://www.nidcd.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.173

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA

This serves as a program announcement of the National Institute on Deafness
and Other Communication Disorders (NIDCD) to expand developmental research in
the auditory and vestibular sensory systems. Investigator initiated
applications responsive to this announcement would promote cellular and
molecular approaches applied to developmental events important for hearing
and balance sensory function.

RESEARCH OBJECTIVES

The formation of the inner ear is extremely complex. Multiple cellular
events involving numerous tissues must progress correctly to form highly
specialized mechanosensory organs, specific innervation patterns, and
exquisitely tuned mechanotransduction sensory structures. This
auditory/vestibular organ and tissue morphogenesis requires cellular
specification followed by fate determination, most likely dependent on
multiple signaling cues from surrounding meso- and endodermal tissues.
During this development, early activation of patterning genes is required to
guide the subsequent commitment and fate determination of auditory and
vestibular cells. Further, this process must be orchestrated with neural
growth and synapse formation to achieve normal hearing and balance function.

The identification of specific cell types and their functional integration
into the developing system provides information relevant to every facet of
auditory and vestibular research, including current and future reparative
therapies. Several accomplishments, such as the completion of detailed cell
lineage and fate mapping analyses, the identification of key cellular
markers, targeting and isolation of homogenous cell populations, purified
reconstitution systems, and functional physiological assays for the
acquisition and evaluation of cell fate and cell differentiation, will be
necessary for progress in this field. Advancement of these areas has been
hampered by a variety of factors, including the need for new and improved
molecular reagents and tools to overcome accessibility problems,
reproducible gene/protein manipulation in vivo and in vitro, and the need
for a more comprehensive representation of model organism systems, such as
Drosophila and Zebrafish, for data mining interconnected signaling pathways
as applied to auditory and vestibular development.

Specific Objectives

The following are examples that might represent projects relevant to the NIDCD
hearing mission. Examples of projects responsive to this PA include but are not
limited to:

o Understanding the developmental process of morphogenic maturation leading
to adult auditory/vestibular structures. Determination of cell movements or
early cell positions as general predictors of final cellular residence.
Determination of possible differences due to species variability.

o Identification of regulatory mechanisms and genes associated with important
structural-functional properties of cell types unique to the inner ear (such
as hair cells, Deiter’s, Hensen’s, Claudius’, interdental, marginal/dark
cells, etc.), and their spatio-temporal establishment from early development
to adult. Advancement of fate mapping and lineage analysis done at single
cell resolution using real-time assessment.

o Expanded developmental work with other model systems, such as Drosophila
and Zebrafish, for identification and functional assessment of gene
orthologues important to hearing and balance function. Data acquisition of
lineage pathways and centralized dissemination of information acquired from
the various multiple model systems.

o Increased isolation and identification of novel auditory/vestibular genes.
Expanded use of microarrays, and libraries generated for single cells and
specific tissue/stage-states.

o Identification of auditory/vestibular gene specific promoters and
associated transcriptional and enhancer regulatory factors. Cre/Flox
expression systems using auditory/vestibular specific promoters. Use of BAC
and/or other transgenic systems.

o Utilization of ChIP-chip assays with transcription factors significant to
auditory and vestibular function.

o In vivo mutational analysis, utilizing both knock in and knock out
technologies. Use of gain and loss functional mutants. Complementation of
functional assays and screens wherever possible for gene/protein function
validation.

o Pursuit of new and existing hearing/balance genes in established mutant
lines of model vertebrate systems. Development of new directed screening
strategies for ear specific markers.

o Gene transfer and delivery technologies to specific targeted auditory and
vestibular areas in animals, as well as organ/cell culture environment(s).

MECHANISM(S) OF SUPPORT

This PA will use the NIH R01 and R21
(http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html)
award mechanism(s). As an applicant, you will be solely responsible for
planning, directing, and executing the proposed project.

This PA uses just-in-time concepts. It also uses the modular budgeting
format. (see http://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, if you are submitting an application with direct costs in each
year of $250,000 or less, use the modular budget format. This program does
not require cost sharing as defined in the current NIH Grants Policy
Statement at
http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part2.htm.

ELIGIBLE INSTITUTIONS

You may submit (an) application(s) if your institution has any of the
following characteristics:

o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign institutions/organizations

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry
out the proposed research is invited to work with their institution to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH programs.

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity to
answer questions from potential applicants. Inquiries may fall into two
areas: scientific/research and financial or grants management issues:

o Direct your questions about scientific/research issues to:

Nancy L. Freeman, Ph.D.
Program Director, Hearing Sciences
National Institutes of Health
National Institute on Deafness and Other Communication Disorders
6120 Executive Blvd., Suite 400
Bethesda, MD 20892-7180
Tel: (301) 402-3458
Fax: (301) 402-6251
Email: FreemanN@mail.NIH.gov

Christopher Platt, Ph.D.
Program Director, Balance/Vestibular Sciences
National Institutes of Health
National Institute on Deafness & Other Communication Disorders
6120 Executive Blvd., Suite 400
Bethesda, MD 20892-7180
Tel: (301)-496-1804
Fax: (301) 402-6251
Email: plattc@nidcd.nih.gov

o Direct your questions about financial or grants management matters to:

Chief, Grants Management Branch
NIH/NIDCD
Executive Plaza South, Room 400B
6120 Executive Boulevard, MSC-7180
Bethesda, MD 20892
Rockville, MD 20852 (express mail)
Telephone: (301) 402-0909
FAX: (301)402-1758

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application
instructions and forms (rev. 5/2001). Applications must have a Dun and
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the
Universal Identifier when applying for Federal grants or cooperative
agreements. The DUNS number can be obtained by calling (866) 705-5711 or
through the web site at http://www.dunandbradstreet.com/. The DUNS number
should be entered on line 11 of the face page of the PHS 398 form. The PHS
398 is available at http://grants.nih.gov/grants/funding/phs398/phs398.html
in an interactive format. For further assistance contact GrantsInfo,
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

The title and number of this program announcement must be typed on line 2 of
the face page of the application form and the YES box must be checked.

APPLICATION RECEIPT DATES: Applications submitted in response to this program
announcement will be accepted at the standard application deadlines, which
are available at http://grants.nih.gov/grants/dates.htm. Application
deadlines are also indicated in the PHS 398 application kit.

SPECIFIC INSTRUCTIONS FOR MODULAR BUDGET GRANT APPLICATIONS: Applications
requesting up to $250,000 per year in direct costs must be submitted in a
modular budget grant format. The modular budget grant format simplifies the
preparation of the budget in these applications by limiting the level of
budgetary detail. Applicants request direct costs in $25,000 modules.
Section C of the research grant application instructions for the PHS 398
(rev. 5/2001) at http://grants.nih.gov/grants/funding/phs398/phs398.html
includes step-by-step guidance for preparing modular grants. Additional
information on modular grants is available at
http://grants.nih.gov/grants/funding/modular/modular.htm.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR:
Applications requesting $500,000 or more in direct costs for any year must
include a cover letter identifying the NIH staff member within one of NIH
institutes or centers who has agreed to accept assignment of the application.

Applicants requesting more than $500,000 must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the
application, i.e., as you are developing plans for the study;

2) Obtain agreement from the IC staff that the IC will accept your
application for consideration for award; and,

3) Identify, in a cover letter sent with the application, the staff member
and IC who agreed to accept assignment of the application.

This policy applies to all investigator-initiated new (type 1), competing
continuation (type 2), competing supplement, or any amended or revised
version of these grant application types. Additional information on this
policy is available in the NIH Guide for Grants and Contracts, October 19,
2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of
the application, including the checklist, and five signed photocopies 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)

APPLICATION PROCESSING: Applications must be mailed on or before the receipt
dates described at
http://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR will
not accept any application in response to this PA that is essentially the
same as one currently pending initial review unless the applicant withdraws
the pending application. The CSR will not accept any application that is
essentially the same as one already reviewed. This does not preclude the
submission of a substantial revision of an unfunded version of an application
already reviewed, but such application must include an Introduction
addressing the previous critique.

Although there is no immediate acknowledgement of the receipt of an
application, applicants are generally notified of the review and funding
assignment within 8 weeks.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of
established PHS referral guidelines. Appropriate scientific review groups
convened in accordance with the standard NIH peer review procedures
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific
and technical merit.

As part of the initial merit review, all applications will:

o Undergo a selection process in which only those applications deemed to have
the highest scientific merit, generally the top half of applications under
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by an appropriate national advisory council
or board

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments, reviewers will be asked to evaluate application in
order to judge the likelihood that the proposed research will have a
substantial impact on the pursuit of these goals. The scientific review
group will address and consider each of the following criteria in assigning
the application’s overall score, weighting them as appropriate for each
application.

o Significance
o Approach
o Innovation
o Investigator
o Environment

The application does not need to be strong in all categories to be judged
likely to have major scientific impact and thus deserve a high priority
score. For example, an investigator may propose to carry out important work
that by its nature is not innovative but is essential to move a field
forward.

SIGNIFICANCE: Does this study address an important problem? 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?

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?

INNOVATION: Does the project employ novel concepts, approaches or methods?
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?

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)?

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?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following
items will be considered in the determination of scientific merit and the
priority score:

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human
subjects and protections from research risk relating to their participation
in the proposed research will be assessed. (See criteria included in the
section on Federal Citations, below).
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of
plans to include subjects from both genders, all racial and ethnic groups
(and subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of
subjects will also be evaluated. (See Inclusion Criteria in the sections on
Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to
be used in the project, the five items described under Section f of the PHS
398 research grant application instructions (rev. 5/2001) will be assessed.

ADDITIONAL REVIEW CONSIDERATIONS

Sharing Research Data

Applicants requesting more than $500,000 in direct costs in any year of the
proposed research are expected to include a data sharing plan in their
application. The reasonableness of the data sharing plan or the rationale for
not sharing research data will be assessed by the reviewers. However,
reviewers will not factor the proposed data sharing plan into the
determination of scientific merit or priority score.

BUDGET: The reasonableness of the proposed budget and the requested period
of support in relation to the proposed research.

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds
with all other recommended applications. The following will be considered in
making funding decisions:

o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Relevance to program priorities

REQUIRED FEDERAL CITATIONS

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and
others, and the importance of the knowledge gained or to be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

DATA AND SAFETY MONITORING PLAN: (NIH Policy for Data and Safety Monitoring,
NIH Guide for Grants and Contracts, June 12, 1998:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

SHARING RESEARCH DATA: Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible.
http://grants.nih.gov/grants/policy/data_sharing
Investigators should seek guidance from their institutions, on issues related
to institutional policies, local IRB rules, as well as local, state and
Federal laws and regulations, including the Privacy Rule. Reviewers will
consider the data sharing plan but will not factor the plan into the
determination of the scientific merit or the priority score.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on
hESCs can be found at http://stemcells.nih.gov/index.asp and at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only
research using hESC lines that are registered in the NIH Human Embryonic Stem
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).
It is the responsibility of the applicant to provide, in the project
description and elsewhere in the application as appropriate, the official NIH
identifier(s)for the hESC line(s)to be used in the proposed research.
Applications that do not provide this information will be returned without
review.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The
Office of Management and Budget (OMB) Circular A-110 has been revised to
provide public access to research data through the Freedom of Information Act
(FOIA) under some circumstances. Data that are (1) first produced in a
project that is supported in whole or in part with Federal funds and (2)
cited publicly and officially by a Federal agency in support of an action
that has the force and effect of law (i.e., a regulation) may be accessed
through FOIA. It is important for applicants to understand the basic scope
of this amendment. NIH has provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the
application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The
Department of Health and Human Services (DHHS) issued final modification to
the “Standards for Privacy of Individually Identifiable Health Information”,
the “Privacy Rule,” on August 14, 2002. The Privacy Rule is a federal
regulation under the Health Insurance Portability and Accountability Act
(HIPAA) of 1996 that governs the protection of individually identifiable
health information, and is administered and enforced by the DHHS Office for
Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside
with the researcher and his/her institution. The OCR website
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including
a complete Regulation Text and a set of decision tools on “Am I a covered
entity?” Information on the impact of the HIPAA Privacy Rule on NIH
processes involving the review, funding, and progress monitoring of grants,
cooperative agreements, and research contracts can be found at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals
for NIH funding must be self-contained within specified page limitations.
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs)
should not be used to provide information necessary to the review because
reviewers are under no obligation to view the Internet sites. Furthermore,
we caution reviewers that their anonymity may be compromised when they
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of "Healthy
People 2010," a PHS-led national activity for setting priority areas. This PA
is related to one or more of the priority areas. Potential applicants may
obtain a copy of "Healthy People 2010" at http://www.healthypeople.gov/.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. Awards are made under the authorization of Sections
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284)
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92). All
awards are subject to the terms and conditions, cost principles, and other
considerations described in the NIH Grants Policy Statement. The NIH Grants
Policy Statement can be found at
http://grants.nih.gov/grants/policy/policy.htm

The PHS strongly encourages all grant recipients to provide a smoke-free
workplace and discourage the 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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