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) 710-0267, 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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