MECHANISMS UNDERLYING THE INNERVATION OF SPECIFIC TASTE RECEPTOR CELLS

Release Date:  November 29, 2000
 
RFA:  DC-01-002

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

Application Receipt Date:  March 26, 2001

THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES 
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED 
WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA.

PURPOSE

The National Institute on Deafness and Other Communication Disorders (NIDCD) 
encourages new and established investigators from a broad range of 
disciplines to submit applications for animal research on the innervation of 
specific types of taste receptor cells by peripheral gustatory ganglion 
cells.  Advances in approaches and in methods of cellular and molecular 
neurobiology, the availability of mutant mouse models, and the results of the 
Human Genome Project provide new opportunities for understanding the 
mechanisms of peripheral innervation as well as the relationships among 
gustatory nerves and specific taste receptor cells.  The purpose of this 
Request for Applications (RFA) is to solicit applications for the study of 
the genetic, molecular and cellular mechanisms underlying migratory events, 
process outgrowth from peripheral gustatory ganglion cells, axon guidance, 
selection of synaptic targets and the innervation of specific taste receptor 
cells.  Research projects supported under this RFA will utilize contemporary 
genetic and molecular biological tools to identify genetic factors, guidance 
molecules, and neurotrophic substances (diffusible and membrane bound) that 
help establish and maintain patterns of innervation in the periphery.  The 
goal of this RFA is to identify the factors that regulate and promote the 
patterns of connections of individual gustatory ganglion cells with specific 
types of taste receptor cells in animal model systems.  The use of 
collaborative teams is encouraged, especially with scientists possessing 
expertise with the type of state-of-the-art methodological approaches that 
are needed for these studies but which have not been routinely applied to the 
taste system. These studies will contribute to our understanding of not only 
the dynamic interrelationship between the gustatory nerves and taste receptor 
cells, but also the connectivity of specific classes of taste receptor cells 
to the central nervous system.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit 
organizations, public and private, such as universities, colleges, hospitals, 
laboratories, units of state or local governments, and eligible agencies of 
the Federal government.  Applications from minority individuals, women, and 
individuals with disabilities are encouraged.  Foreign organizations or 
organizations in foreign countries are not eligible; subcontracts to foreign 
organizations are allowable, with sufficient justification.

Submission of an application under this RFA precludes submission of any other 
application containing substantially the same research proposal during the 
same funding cycle. In addition, this award 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.
 
MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) 
Exploratory/Developmental Grants (R21) mechanism. This mechanism offers 
support for taste research that lacks a historical precedent or sufficient 
preliminary data.  Areas of taste research in which there is a sufficient 
historical basis or sufficient preliminary data to support the submission of 
a standard research project grant application do not qualify under this RFA.   
The applicant has the responsibility to provide evidence of the feasibility 
of the proposed project and for developing a demonstrably sound research 
plan.  It is expected that the data generated by these grants, if promising, 
will serve as a basis for a more extensive follow-up investigation, typically 
pursued through the submission of an R01 grant application.  It should be 
noted that the level of funding and the submission date established for this 
specific RFA differ from those announced for the NIDCD's High Impact 
Research/Feasibility Studies (R21) grant mechanism.  Responsibility for the 
planning, direction, and execution of the proposed project will be solely 
that of the applicant.  Grant applications received in response to this RFA 
are limited to a maximum of $100,000 direct costs per year, two years in 
duration, and are not renewable.  However, an application whose direct cost 
budget includes Facilities and Administration (F&A) costs associated with 
subcontract/consortium activity may exceed the $100,000 ceiling by the amount 
of one module ($25,000). The anticipated award date is September 30, 2001. 

Specific application instructions have been modified to reflect "MODULAR 
GRANT" streamlining efforts being examined by the NIH. The modular grant 
concept establishes specific modules in which direct costs may be requested 
as well as a maximum level for requested budgets. Only limited budgetary 
information is required under this approach. It is anticipated that these 
changes will reduce the administrative burden for the applicants, reviewers 
and Institute staff. Complete and detailed instructions and information on 
Modular Grants can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm.
.
FUNDS AVAILABLE

This RFA is a one-time solicitation.  It is anticipated that about $750,000 
in Total Costs (including all direct and facilities and administrative costs) 
will be available for this initiative in Fiscal Year 2001 for the award of 
five to seven grants.  Awards pursuant to this RFA are contingent upon the 
availability of funds.

RESEARCH OBJECTIVES

Background

Taste quality coding and perception involves the dynamic interaction between 
the sensitivities of individual taste receptor cells and the physiological 
response profiles of first-order and more central gustatory neurons.  Unlike 
the olfactory system where the receptor cells are specialized neurons that 
project centrally, taste receptor cells are epithelial in origin and are in 
synaptic contact with gustatory cranial nerves that project into the 
brainstem.  Therefore, a critical issue in taste coding is an understanding 
of the mechanisms that govern the patterns of connections between gustatory 
nerves and the classes of taste receptor cells that are activated by sweet-, 
salty-, sour-, and bitter-tasting stimuli.  The development of concepts, 
approaches and methods of contemporary neurobiology has provided the 
opportunity to learn more about the genetic, molecular and cellular 
mechanisms of peripheral innervation of specific types of taste receptor 
cells.  For example, cell culture techniques are available to isolate 
neurotrophic factors and to monitor axon process outgrowth; DNA microarray 
profiling of gene expression can facilitate the identification of relevant 
genes; and mutant mouse models have the potential to explore the development 
of the taste system and the innervation of taste receptor cells under altered 
genetic conditions.

The purpose of this RFA is to encourage the submission of feasibility studies 
with the potential for leading to a technological, methodological, or 
conceptual breakthrough in our understanding of the innervation of specific 
types of taste receptor cells and their connections to the central nervous 
system.  This research may involve: 1) pilot testing of novel scientific 
experimental hypotheses, 2) the development of novel techniques or 
technologies, and/or 3) the acquisition of a body of data (e.g., a genetic 
database). The following examples are representative areas of interest:

1. Profiling of gene expression in the gustatory peripheral ganglia during 
the critical developmental stages of the peripheral taste system, with 
emphasis on genes known to play a role in axon guidance and pathway 
finding.

2.    An analysis of the cellular and/or molecular mechanisms that stimulate 
axon outgrowth and channeling to the tongue and/or palate from the 
gustatory peripheral ganglia.

3.    The identification of neurotrophin growth factors (diffusible and 
membrane bound) and their receptors that facilitate the selection of 
synaptic targets at the level of the taste receptor cell and/or taste bud.

4. Characterization of patterns of innervation and synapse formation between 
gustatory fibers and populations of taste receptor cells that express 
specific types of identifiable taste receptors. 



APPLICATION PROCEDURES

Applicants are strongly encouraged to contact program staff listed under 
INQUIRIES with any questions regarding the responsiveness of their proposed 
project to the goals of this RFA. 

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for this RFA.  These forms are available at most institutional 
offices of sponsored research and from the Division of Extramural Outreach 
and Information Resources, National Institutes of Health, 6701 Rockledge 
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-0714, Email: 
GrantsInfo@nih.gov.  The application form is also available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html. The instructions in 
the PHS 398 application kit must be adhered to, except where they have been 
modified by the following Supplemental Instructions.

The title and number of this RFA, DC-01-002,  MECHANISMS UNDERLYING THE 
INNERVATION OF SPECIFIC TASTE RECEPTOR CELLS, must be typed on line 2 of the 
face page of the application form and the YES box must be marked.  The RFA 
label found in PHS 398 (rev. 4/98) must be stapled to the bottom of the face 
page of the original application.

The completed original application and three copies (send no appendices) must 
be submitted to:

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

Send two additional copies of the application and five sets of appendices 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
Rockville, MD  20892-7180 
Rockville, MD 20852 (for express/courier mail)

The application receipt date is March 26, 2001; applications received after 
this date will be returned to the applicant. 

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.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.


RESEARCH PLAN:

Do not exceed a total of 10 pages for the research plan, Sections a-d.  This 
limitation includes the introductory paragraph described below, tables and 
figures, but not Sections e-i.  Do not use the appendix to circumvent the 10-
page limit by including tables or figures in the appendix that should appear 
in the research plan.

Amply justify the designation of the application as a feasibility study in an 
introductory paragraph at the beginning of the research plan.  Justify why 
the project would not be appropriate for submission as a traditional research 
grant and how this project, if fruitful, would enable the applicant to craft 
a research program appropriate for submission as a full-scale research grant 
application.  Label this paragraph, “Justification for Feasibility Studies ”.  
Applications that lack the introductory justification or exceed the page 
limitation will not be reviewed and will be returned to the applicant.

Some applications submitted in response to this RFA may be design-driven 
(e.g., development of novel technologies) or data-driven (e.g., database 
acquisition) rather than problem-driven (e.g., testing of scientific 
hypotheses).  In the first two cases, the Specific Aims should state the 
technique/technology development needs or the data acquisition needs driving 
the research rather than the experimental hypotheses to be tested.

SPECIFIC APPLICATION INSTRUCTIONS FOR MODULAR GRANTS

The modular grant concept 
(http://grants.nih.gov/grants/funding/modular/modular.htm)
establishes specific modules in which direct costs may be requested as well 
as a maximum level for requested budgets. Only limited budgetary information 
is required under this approach.  The just-in-time concept allows applicants 
to submit certain information only when there is a possibility for an award.  
It is anticipated that these changes will reduce the administrative burden 
for the applicants, reviewers and Institute staff.  The research grant 
application form PHS 398 (rev. 4/98) is to be used in applying for these 
grants, with the modifications noted below.  Modular Grant applications will 
request direct costs in $25,000 modules, up to a total direct cost request of 
$100,000 per year.  The total direct costs must be requested in accordance 
with the program guidelines and the modifications made to the standard PHS 
398 application instructions described below.

BUDGET INSTRUCTIONS

PHS 398

o  FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs 
(in $25,000 increments up to a maximum of $100,000 or $125,000, the latter in 
the case of consortia for contractual activity) and Total Costs [Modular 
Total Direct plus Facilities and Administrative (F&A) costs] for the initial 
budget period. Items 8a and 8b should be completed, indicating the Direct and 
Total Costs for the entire proposed period of support.

o  DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 
4 of the PHS 398. It is not required and will not be accepted with the 
application.

o  BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the
categorical budget table on Form Page 5 of the PHS 398. It is not required 
and will not be accepted with the application.

o  NARRATIVE BUDGET JUSTIFICATION - Use a Modular Grant Budget Narrative 
page. (See: http://grants.nih.gov/grants/funding/modular/modular.htm for 
sample pages.) At the top of the page, enter the total direct costs requested 
for each year.

o  Under Personnel, list all project personnel, including their names, 
percent of effort, and roles on the project. No individual salary information 
should be provided.

o  For Consortium/Contractual costs, provide an estimate of total costs 
(direct plus facilities and administrative) for each year, each rounded to 
the nearest $1,000. List the individuals and organizations with whom 
consortium or contractual arrangements have been made, the percent effort of 
all personnel, and the role on the project.  Indicate whether the 
collaborating 
institution is foreign or domestic.  The total cost for a 
consortium/contractual arrangement is included in the overall requested 
direct cost amount for the application. Under these circumstances, the latter 
may exceed the $100,000 maximum by one module ($25,000). Provide an 
additional narrative budget justification for any variation in the number of 
modules or direct 
cost amount requested across the two-year grant period.

o  BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by
reviewers in the assessment of each individual's qualifications for a 
specific role in the proposed project, as well as to evaluate the overall 
qualifications of the research team.  A biographical sketch is required for 
all project personnel, following the instructions below.  No more than three 
pages may be used for each person.  A sample biographical sketch may be 
viewed at: http://grants.nih.gov/grants/funding/modular/modular.htm

- Complete the educational block at the top of the form page
- List position(s) and any honors
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years
- List selected peer-reviewed publications, with full citations

o  CHECKLIST - This page should be completed and submitted with the 
application. If the F&A rate agreement has been established, indicate the 
type of agreement and the date. It is important to identify all exclusions 
that were used in the calculation of the F&A costs for the initial budget 
period and all future budget years.

o  The applicant should provide the name and phone number of the individual 
to contact concerning fiscal and administrative issues, if additional 
information is necessary following the initial review.


REVIEW CONSIDERATIONS

All applications will be examined for completeness by CSR and for 
responsiveness to this RFA by NIDCD staff.  Incomplete and non-responsive 
applications will be returned to the applicant. Complete and responsive 
applications will be reviewed for scientific and technical merit in 
accordance with the standard NIH procedures by a review group convened by the 
NIDCD.  As part of the initial review, all applications will receive a 
written critique.  Those applications deemed to have the highest merit, 
generally the top half of applications under review, will be discussed, 
assigned a priority score, and receive a second level of review by the NDCD 
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 the application in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of these goals.  Each 
of these criteria will be addressed and considered in assigning the overall 
score, weighting them as appropriate for each application.  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.

(1) Significance:  Does this feasibility study have the potential to 
significantly impact the scientific enterprise, and if so, to what degree?  
If the aims of the application are achieved, how will scientific knowledge be 
advanced? Will a successful outcome from this feasibility study lead directly 
to more extensive follow-up studies that would likely achieve the long-term 
goals of this application?

(2) 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?  Does the application contain a demonstrably sound plan 
designed to assess the feasibility of the pilot project?

(3) Innovation:  Does the project employ novel concepts, approaches or 
method? Are the aims original and innovative?  Does the project challenge 
existing paradigms or develop new methodologies or technologies?  Does the 
project generate a body of data that provides a foundation for important new 
research directions?

(4) 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)?

(5)  Environment:  Does the scientific environment in which the work will be 
conducted contribute to the probability of success?  Is there evidence of 
institutional support for the research? Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements?

(6)  The reasonableness of the proposed budget and the project’s duration in 
relation to the proposed research.

(7)  The adequacy of the measures proposed for protection of animals and/or 
the environment, to the extent they may be adversely affected by the research 
proposed in the application.

AWARD CRITERIA

The anticipated date of award is September 30, 2001. The following will be 
considered in making funding decisions:

o  Quality of the proposed project as determined by rigorous scientific peer 
review.

o  Promise of the proposed project to accomplish the goals of this RFA.

o  Program priorities and program balance.

o Availability of funds.

SCHEDULE

Application Receipt Date:  March 26, 2001 
Scientific Review Date:    June/July, 2001
Advisory Council Date:     September 21, 2001
Anticipated Award Date:    September 30, 2001

INQUIRIES

NIDCD staff welcome the opportunity to clarify any issues or questions about 
this initiative from potential applicants. Direct inquiries regarding 
programmatic issues, including eligibility and responsiveness, to:

Barry J. Davis, Ph.D.
Scientific Programs Branch
National Institute on Deafness and Other Communication Disorders
Room 400C,  MSC 7180
6120 Executive Blvd. 
Bethesda, MD 20892-7180
Telephone: (301) 402-3464
FAX: (301) 402-6251
Email: Barry_Davis@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Sherry Dabney
Grants Management Branch
Division of Extramural Research
National Institute on Deafness and Other Communication Disorders 
Room 400B,  MSC 7180
6120 Executive Boulevard 
Bethesda, MD  20892-7180
Telephone:  (301) 402-0909
FAX:  (301) 402-1757
Email: Dabneys@nidcd.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 Act, 
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 
241 and 285) and administered under NIH grants policies and Federal 
Regulations 42 CFR 52 and 45 CFR Part 74 or 92. This program is not subject 
to the intergovernmental review requirements of Executive Order 12372 or 
Health Systems Agency review.  Awards will be administered under PHS policy 
as stated in the NIH Grants Policy Statement (October 1, 1998).

The PHS strongly encourages all grant and contract recipients to provide a 
smoke-free workplace and promote the non-use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking 
in certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.


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