PROTEOMICS IN AUDITORY DEVELOPMENTAL AND DISEASE PROCESSES
RELEASE DATE: July 9, 2003
PA NUMBER: PA-03-151
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-06-366) 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 All R01 Applications: June 13, 2006
National Institute on Deafness and Other Communication Disorders (NIDCD)
(http://www.nidcd.nih.gov)
THIS PA CONTAINS THE FOLLOWING INFORMATION
o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support
o Eligible Institutions
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS PA
This serves as an initial program announcement of the National Institute on
Deafness and Other Communication Disorders (NIDCD) to expand support of
proteomic research in the auditory system. This announcement seeks to
promote the use of proteomic technologies to investigate the molecular and
cellular mechanisms of normal/abnormal auditory development, and maintenance,
as well as specific disease states of hearing tissues and sensory organs.
The utilization, development and improvement of innovative proteomic
technologies to address these issues are encouraged through applications
relevant to these biological areas.
RESEARCH OBJECTIVES
High throughput technologies with the singular goal of acquiring the most
inclusive collection of representative genomic sequence, transcript, and/or
protein, is the current view of biomedical research. Data sets of transcript
and protein expression provide investigators a comprehensive cellular
snapshot of existing proteins of a given protein complex, cell type, tissue
and environmental condition. While both sequence and transcript profiling
have made significant advances in their technologies and utilization, there
remains a need to comprehensively catalog protein content within many
important cell types and tissues of the auditory sensory system.
The molecular exploration of hearing has identified an exquisite array of
developing sensory organs and tissues. The identification of genes and the
regulation of their corresponding proteins are important to normal and
abnormal developmental processes, genetic disorders and environmental noise
trauma. Numerous cell types, and their substructures, unique to the inner
ear, such as hair cells, Deiters, Hensen, Claudius', interdental, and
marginal/dark cells, have been virtually unexplored from a proteomic
perspective. Additionally, middle ear infections (otitis media) and other
diseases of the auditory system such as otosclerosis and cholesteatoma, pose
important clinical challenges involving the identification of causative
extrinsic factors, infectious organisms and the complexity of host response.
Microarrays and other transcript sensing technologies have been used
successfully to increase the number of candidate genes, but clearly there
remain interpretive limitations to the correlative protein function. These
assays bypass and/or inadequately address such substantial issues of post-
translational modifications, turnover, and alternately spliced transcripts.
Proteomic approaches have become increasingly successful and gaining utility
for studying complex biological problems relevant to the auditory system.
Technologies using tandemly coupled two-dimensional (2-DE) gel
electrophoresis and mass spectrometry (MS) for protein peptide identification
(PMF-peptide mass fingerprinting) combined with the differentially isotopic
labeling of protein allows profile comparisons between two different cellular
states (e.g. disease versus non-disease). There are numerous variations of
protein separation matrices as well as dispersion and analysis, e.g. ESI/HPLC,
ESI-TOF/ ESI-MS/MS, MALDI-TOF, etc., and the designation of use is often
preferenced by the biological parameters of the sample. Other types of high
throughput assays, such as cell biochips encompassing both antigen and
antibody based arrays, yeast two-hybrid systems, co-immunoprecipitations,
used in combination with 2-DE/MS/PMF (or other) followed by bioinformatical
analysis allow even further specialized approaches of biopolymer
identification for both proteomic and subproteomic data. The attempt to
generate a comprehensive proteome atlas has limitations with regard to
sensitivity and detection, as well as, sufficient material acquisition;
improvements have increased measurements from picomoles, to femtomoles, with
some reports of attomole measurements allowing smaller sample sizes to be
accurately measured.
Proteomic roadmaps display the complex interactiveness of signal transduction
pathways and the interconnectedness of protein associations. They will
provide the working protein profiles that identify the numerous interolog
relationships of a given interactome, and allow comparison of protein species
in a comprehensive manner. There will continue to be the need for improved
technologies and novel proteomic approaches that enhance sensitivity and
increase comprehensiveness. These technological developments would be of
particular interest when accomplished through projects directed at
understanding or solving problems related to cells, organs and/or diseases of
the auditory system.
The following examples are not meant to be comprehensive or restrictive, but
rather represent projects relevant to the NIDCD hearing mission. Examples of
projects responsive to this PA include but are not limited to:
o Proteomic analysis of specific cell types of the inner ear and/or their
subcellular structures
o Proteomic analysis of specific otocyst cell/tissue types through a variety
of developing stages
o Comparative analysis between proteome and transcriptome of a defined
auditory cell and/or tissue type; comparative determination between proteomic
and transcriptome results
o Comparative analysis of infection state in middle ear tissue, cell type, in
response to invasion with otitis media pathogens; comparative proteomic
analysis of infectious pathogens involved in middle ear infections upon
biofilm or infection stimulus
o Proteomic analysis of auditory genetic disorders, environmental noise or
drug trauma; biological and/or clinical in design
o Proteomic analysis of purified and/or in vitro propagated cultures of
putative auditory progenitor cells
o Use of proteomic approaches to study the signal transduction networks
related to transcription factors, cell surface receptors, growth factors, and
other biomarkers relevant to auditory development
o Proteomic identification of novel signaling molecules and pathways involved
in cell development, differentiation, communication, function and destruction,
as applied to auditory signaling processes
o Development of novel proteomic bioinformatics as related to annotating
genomic and protein sequence information for auditory function
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
mechanisms. 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 as well
as the non-modular budgeting formats (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 format. Otherwise follow the
instructions for non-modular research grant applications. This program
does not require cost sharing as defined in the current NIH Grants
Policy Statement at
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.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
o Faith-based or community-based 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
Inquiries concerning this PA are strongly recommended to discuss scientific
issues with potential applicants. Inquiries may fall into two areas:
scientific/research, and financial/grants management issues:
o Direct your questions about scientific/research issues to:
Nancy L. Freeman, Ph.D.
Scientific Program Director
National Institutes of Health
National Institute on Deafness and Other Communication Disorders
Executive Plaza South-400C
6120 Executive Blvd. MSC-7180
Bethesda, MD 20892-7180
Email: nancy_freeman@NIH.gov
Tel: (301) 402-3458
Fax: (301) 402-6251
o Direct your questions about financial/grants management matters relevant
to:
Ms. Sara Stone
Chief, Grants Management Branch
Division of Extramural Research
National Institutes of Health
National Institute on Deafness and Other Communication Disorders
Executive Plaza South-400C
6120 Executive Blvd. MSC-7180
Bethesda, MD 20892-7180
Email: stones@nidcd.nih.gov
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). 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) 710-0267, Email: GrantsInfo@nih.gov.
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 R21 APPLICATIONS: All application
instructions outlined in the PHS 398 application kit are to be followed,
with the following requirements for R21 applications
http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html:
1. R21 applications will use the "MODULAR GRANT" and "JUST-IN-TIME"
concepts, with direct costs of up $275,000 for the two year period.
For example, the applicant may request $100,000 in the first year and
$175,000 in the second year. The request should be tailored to the
needs of the project. Normally, no more than $200,000 may be requested
in any single year.
2. Although preliminary data are not required for an R21 application,
they may be included.
3. Sections a-d of the Research Plan of the R21 application may not
exceed 15 pages, including tables and figures.
4. R21 appendix materials should be limited, as is consistent with the
exploratory nature of the R21 mechanism, and should not be used to
circumvent the page limit for the research plan. Copies of appendix
material will only be provided to the primary reviewers of the
application and will not be reproduced for wider distribution. The
following materials may be included in the appendix:
o Up to five publications, including manuscripts (submitted or accepted
for publication), abstracts, patents, or other printed materials
directly relevant to the project. These may be stapled as sets.
o Surveys, questionnaires, data collection instruments, and clinical
protocols. These may be stapled as sets.
o Original glossy photographs or color images of gels, micrographs,
etc., provided that a photocopy (may be reduced in size) is also
included within the 15 page limit of items a-d of the research plan
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications
requesting up to $250,000 per year in direct costs must be submitted in
a modular grant format. The modular 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)
The title, PROTEOMICS IN AUDITORY DEVELOPMENTAL AND DISEASE PROCESSES, and
the number of this announcement, PA-03-151, must be typed on line 2 of the
face page of the application form and the YES box must be marked.
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
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. An appropriate scientific review
group 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 Receive a written critique
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 second level review by the National Deafness and
Communication Disorders Advisory Council.
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 discuss the
following aspects of your application in order to judge the likelihood
that the proposed research will have a substantial impact on the
pursuit of these goals:
o Significance
o Approach
o Innovation
o Investigator
o Environment
The scientific review group will address and consider each of these
criteria in assigning your application's overall score, weighting them
as appropriate for each application. Your 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,
you may propose to carry out important work that by its nature is not
innovative but is essential to move a field forward.
(1) SIGNIFICANCE: Does your study address an important problem? If the
aims of your application are achieved, how do they advance scientific
knowledge? What will be the effect of these studies on the concepts or
methods that drive this field?
(2) APPROACH: Are the conceptual framework, design, methods, and
analyses adequately developed, well integrated, and appropriate to the
aims of the project? Do you acknowledge potential problem areas and
consider alternative tactics?
(3) INNOVATION: Does your project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does your project
challenge existing paradigms or develop new methodologies or
technologies?
(4) INVESTIGATOR: Are you appropriately trained and well suited to
carry out this work? Is the work proposed appropriate to your
experience level as the principal investigator and to that of other
researchers (if any)?
(5) ENVIRONMENT: Does the scientific environment in which your 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).
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.
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
MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research
components involving Phase I and II clinical trials must include
provisions for assessment of patient eligibility and status, rigorous
data management, quality assurance, and auditing procedures. In
addition, it is NIH policy that all clinical trials require data and
safety monitoring, with the method and degree of monitoring being
commensurate with the risks (NIH Policy for Data Safety and Monitoring,
NIH Guide for Grants and Contracts, June 12, 1998:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the
policy of the NIH that women and members of minority groups and their
sub-populations must be included in all NIH-supported clinical research
projects unless a clear and compelling justification is provided
indicating 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 clinical research should read the AMENDMENT
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research - Amended, October, 2001," published in the NIH Guide
for Grants and Contracts on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of
clinical research; updated racial and ethnic categories in compliance
with the new OMB standards; clarification of language governing NIH-
defined Phase III clinical trials consistent with the new PHS Form 398;
and updated roles and responsibilities of NIH staff and the extramural
community. The policy continues to require for all NIH-defined Phase
III clinical trials that: a) all applications or proposals and/or
protocols must provide a description of plans to conduct analyses, as
appropriate, to address differences by sex/gender and/or racial/ethnic
groups, including subgroups if applicable; and b) investigators must
report annual accrual and progress in conducting analyses, as
appropriate, by sex/gender and/or racial/ethnic group differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS: The NIH maintains a policy that children (i.e., individuals
under the age of 21) must be included in all human subjects research,
conducted or supported by the NIH, unless there are scientific and
ethical reasons not to include them. This policy applies to all initial
(Type 1) applications submitted for receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should
read the "NIH Policy and Guidelines" on the inclusion of children as
participants in research involving human subjects that is available at
http://grants.nih.gov/grants/funding/children/children.htm.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject
participants for all investigators submitting NIH proposals for
research involving human subjects. You will find this policy
announcement in the NIH Guide for Grants and Contracts Announcement,
dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
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 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).
Those who must comply with the Privacy Rule (classified under the Rule
as "covered entities") must do so by April 14, 2003 (with the
exception of small health plans which have an extra year to comply).
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.health.gov/healthypeople.
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance No. 93.173 and is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review. Awards are made under authorization of
Sections 301 and 405 of the Public Health Service Act as amended (42
USC 241 and 284) and administered under NIH grants policies described
at http://grants.nih.gov/grants/policy/policy.htm under Federal
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.
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.
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