STEM CELL POTENTIAL OF THE MAMMALIAN OLFACTORY EPITHELIUM

RELEASE DATE:  November 18, 2002 (see NOT-DC-03-003)  

RFA:  DC-03-002

LETTER OF INTENT RECEIPT DATE:  February 3, 2003

APPLICATION RECEIPT DATE:  March 11, 2003 

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

THIS REQUEST FOR APPLICATIONS (RFA) CONTAINS THE FOLLOWING INFORMATION

o Purpose of the RFA
o Research Objectives
o Mechanism of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Sending an Application to the NIH
o Research Plan
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citation

PURPOSE 

The National Institute on Deafness and Other Communication Disorders (NIDCD) 
supports clinical and basic biomedical research in the area of human 
olfaction (smell).  The partial or complete loss of smell (anosmia) affects 
approximately 2.5 million people and poses serious health risks as the 
presence of rancid food, toxic odors and smoke often go undetected.  The loss 
of smell adversely affects the perceived flavor of foods, which impacts on 
diet and nutrition, especially in the elderly.  The clinical treatment of 
anosmia will require a better understanding of the mechanisms that regulate 
differentiation, proliferation and the injury response of precursor, 
multipotent stem cells in the olfactory epithelium .  

The NIDCD invites applications for exploratory pilot studies focused on stem 
cell biology, using the precursor, multipotent stem cells of the mammalian 
olfactory epithelium as a model system.  The proposed research should involve 
the testing of novel hypotheses or the development of new techniques or 
methodologies that will mainly benefit future stem cell research in the 
olfactory system, but has the potential to increase our understanding of stem 
cell biology elsewhere in the brain.  The proposed areas of investigation 
should lack the pilot data needed for the submission of a regular research 
grant; however, the soundness and feasibility of the research plan must be 
demonstrated.  It is intended that, if promising, the pilot data generated by 
these exploratory grants may serve as a basis for a more extensive follow-up 
investigation (e.g., an investigator-initiated R01 grant application).  The 
NIDCD encourages applications from investigators who are conducting research 
outside the field of olfaction and possess expertise in stem cell biological 
research, and who are using methodological approaches that have not been 
typically applied to but which would greatly promote scientific progress 
within the field of olfaction.  

RESEARCH OBJECTIVES

Olfactory receptor neurons are exposed to the external environment and are 
susceptible to toxic airborne chemicals, infectious pathogens and physical 
damage following frontal head trauma.  Olfactory receptor neurons are 
ordinarily replaced periodically throughout life and also have the capacity 
to proliferate in response to acute injury.  Such replacement and 
proliferation are possible due to the presence of precursor, multipotent stem 
cells in the olfactory epithelium.  These precursor cells possess the ability 
to differentiate into either mature olfactory receptor neurons or non-
neuronal support cells.  An understanding of the injury response of the 
olfactory epithelium will require the study of the mechanisms that regulate 
the differentiation and proliferation of these precursor cells.  Furthermore, 
the olfactory epithelium represents a readily accessible source of an 
abundant sample of multipotent stem cells for studies focused on stem cell 
biological research or technology development.

The regenerative capacity of the olfactory epithelium, its reconstitution 
after injury and the reinnervation of the olfactory bulb have been studied 
extensively.   Less is known about the genetic and molecular events and local 
environmental trophic influences that control and up-regulate precursor cell 
activity. The olfactory system affords the opportunity to investigate the 
facile nature of one part of the nervous system in the hope to better 
understand and to improve the regenerative capabilities of other regions.   
This RFA is soliciting applications focused on the genetic, molecular and 
cellular mechanisms that regulate the lineage, differentiation and 
proliferation of the multipotent stem cells in the olfactory epithelium.  
Research efforts applying the contemporary tools of stem cell biology are of 
high importance.  Areas of special interest include, but are not limited to:

o  The genetic and molecular control of the lineage pathway of olfactory 
precursor cells
o  The use of gene targeting or tissue-specific reporters to identify the 
various stages of neuronal differentiation
o  The identification of signaling pathways, growth factors and trophic cues 
that enhance functional integration within olfactory or other neural tissue 
o  The development of tissue culture, harvesting, and cell sorting 
technologies to ensure an ample supply of purified precursor cells
o  The utility of using embryonic, hemopoietic and mesenchymal stem cells in 
a compromised olfactory system

MECHANISM OF SUPPORT 

This RFA will use the NIH Exploratory/Developmental Grants (R21) mechanism.  
As an applicant, you will be solely responsible for planning, directing, and 
executing the proposed project.  This RFA is a one-time solicitation.  Future 
unsolicited, competing-continuation applications based on this project will 
compete with all investigator–initiated applications and will be reviewed 
according to the customary peer review procedures. An individual may submit 
only one application in response to this RFA as the principal investigator.  
The anticipated award date is December 1, 2004.

This RFA uses just-in-time concepts, including the approved use of laboratory 
animals (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-064.html).  
It also uses the modular budgeting format.
(see http://grants.nih.gov/grants/funding/modular/modular.htm).   

FUNDS AVAILABLE

The NIDCD intends to commit approximately $1,000,000 in FY04 to fund 6 to 7 
new grants in response to this RFA.  An applicant may request a project 
period of up to 2 years and a budget for direct costs of up to $100,000 per 
year.  Because the nature and scope of the proposed research will vary from 
application to application, it is anticipated that the size and duration of 
each award will also vary. Although the financial plans of the NIDCD provide 
support for this program, awards pursuant to this RFA are contingent upon the 
availability of funds and the receipt of a sufficient number of meritorious 
applications. At this time, it is not known if this RFA will be reissued.

ELIGIBLE INSTITUTIONS 

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

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

Foreign organizations or organizations in foreign countries are not eligible; 
subcontracts to foreign organizations are allowable, with sufficient 
justification.

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.

SPECIAL REQUIREMENTS

The amount of pilot data that typically accompanies an R01 application is not 
required as a part of this initiative.  Nonetheless, the applicant has the 
responsibility to provide sufficient pilot data to demonstrate the soundness 
and feasibility of the research plan.  Furthermore, the appropriate expertise 
of key personnel and collaborators to pursue such novel research must be 
evident.  Individuals working outside the area of olfaction with expertise in 
stem cell research are encouraged to apply. 

This announcement highly encourages collaboration between stem cell biologists 
and the olfactory research community.

Submission of an application under this RFA precludes submission of any other 
application to the NIH containing substantially the same research proposal.  
In addition, awards made in response to this initiative may not be used to 
supplement research projects currently supported by Federal or non-Federal 
funds, or to provide interim support of projects under review by the 
Department of Health and Human Services.

Applications in response to this RFA with the intent to use human embryonic 
stem cells (hESC) must comply with federal guidelines.  A cover letter signed 
by the principal investigator, appropriate institutional official and business 
office, acknowledging review and approval of the grant application proposing 
human embryonic stem cell research must be included.  Within the Description 
on page 2 all applications must indicate the official identifier(s) for the 
appropriate hESC line(s) as found in the NIH Registry (http://escr.nih.gov/).  
In addition, compliance to all of the federal guidelines must be satisfied.  
These NIH guidelines are listed at,
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-049.html.
Applications not including this information will be 
returned without further consideration.  Answers to frequently asked questions 
about hESC may be found at: http://grants.nih.gov/grants/stem_cell_faqs.htm

WHERE TO SEND INQUIRIES

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

o Direct your questions about scientific/research issues to:

Dr. Barry Davis
Director
Taste and Smell Program
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-C, MSC-7180
Rockville, MD  20892-7180
Telephone: (301) 402-3464
FAX: (301) 402-6251
Email: barry_davis@nih.gov

o Direct your questions about peer review issues to: 

Dr. Craig Jordan
Chief, Scientific Review Branch
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-C, MSC-7180
Rockville, MD  20892-7180
Telephone:  301-496-8683
FAX: (301) 402-6250
Email: jordanc@nih.gov

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

Sara Stone
Chief, Grants Management Branch
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-B, MSC 7180
Rockville, MD  20892-7180
Telephone:  (301) 402-0909
FAX:  (301) 402-1758
Email: stones@nih.gov

LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows institute staff to estimate the potential review workload and 
to plan the review.
 
The letter of intent is to be sent by February 3, 2003.  The letter of intent 
should be sent to:

Dr. Barry Davis
Director
Taste and Smell Program
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-C, MSC-7180
Rockville, MD  20892-7180

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) 435-0714, 
Email: GrantsInfo@nih.gov.

SENDING AN APPLICATION TO THE NIH

Submit a signed, typewritten original of the application, including the 
checklist, and three 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, STEM CELL POTENTIAL OF THE MAMMALIAN OLFACTORY EPITHELIUM, and the 
number of this announcement, RFA-02-005, must be typed on line 2 of the face 
page of the application form and the YES box must be marked.

Send two additional copies of the application and five sets of appendices (if 
applicable) to:

Chief, Scientific Review Branch
Division of Extramural Research
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)

RECEIPT AND REVIEW SCHEDULE

Application Receipt Date:  March 11, 2003
NIDCD Committee Review:  June/July, 2003
Council Review:  September, 2003 
Earliest Funding:  December, 2003

APPLICATION PROCESSING: Applications must be received by or mailed before the 
receipt date listed on the face page of the RFA.  The Center for Scientific 
Review (CSR) 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 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 an application must include an Introduction 
addressing the previous critique.

RESEARCH PLAN

The applications submitted in response to this RFA must test specific 
hypotheses or develop new technologies or methodologies.  Data-driven (e.g., 
database management, mining, or distribution) applications are not eligible.

The current RFA provides nonrenewable awards for up to two years of support 
and up to $100,000 per year in direct costs.  The total cost (Direct plus 
Facilities and Administrative costs (F & A costs) for any 
consortium/contractual arrangement must be included within the overall 
requested direct cost amount for the application, which can not exceed 
$100,000.

PEER REVIEW PROCESS

All applications will be examined for completeness by the CSR and for 
responsiveness by NIDCD staff.  Incomplete and/or non-responsive applications 
will be returned to the applicant without further consideration.  
Applications failing to comply with NIH grant format guidelines 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-037.html) will be 
returned.  Complete and responsive applications will be reviewed for 
scientific and technical merit in accordance with standard NIH procedures by 
a review group convened by the NIDCD Scientific Review Branch.

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 Other 
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.  

(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, your 
application will also be reviewed with respect to the following:

PROTECTIONS:  The adequacy of the proposed protection for humans, animals, or 
the environment, to the extent they may be adversely affected by the project 
proposed in the application.

INCLUSION:  The adequacy of plans to include subjects from each gender, all 
racial and ethnic groups (and subgroups), and children, as appropriate for 
the scientific goals of the research.  Plans for the recruitment and 
retention of subjects will also be evaluated. (See Inclusion Criteria 
included in the section on Federal Citations, below)

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

OTHER REVIEW CRITERIA:  

o Does the proposed research represent a test of novel ideas, techniques or 
methods that will impact the concepts that drive the field of olfactory stem 
cell research?

o Will the successful outcome of the proposed studies likely generate 
sufficient data to pursue follow-up studies and lead to a full-scale research 
grant application? 

AWARD CRITERIA

Applications submitted in response to a RFA 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 

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://grants.nih.gov/grants/stem_cells.htm 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.

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 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 grants 
policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74.  

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.
http://grants.nih.gov/grants/guide/pa-files/PA-02-015.html. 

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