RFA-HL-99-013: RAT GENOME DATABASE

Department of Health
and Human Services (HHS)

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RAT GENOME DATABASE Release Date: March 5, 1999 RFA: HL-99-013 P.T. National Heart, Lung and Blood Institute National Institute of Neurological Disorders and Stroke National Cancer Institute National Center for Research Resources National Human Genome Research Institute National Institute on Alcohol Abuse and Alcoholism National Institute of Child Health and Human Development National Institute of Dental and Craniofacial Research National Institute of Diabetes and Digestive and Kidney Diseases National Institute on Drug Abuse National Institute of Environmental Health Sciences National Institute of Mental Health Letter of Intent Receipt Date: April 1, 1999 Application Receipt Date: April 26, 1999 PURPOSE In response to the recommendations of the Rat Genome Advisory Committee and the Report of the NIH Model Organism Database Workshop (http://www.nhlbi.nih.gov/) the NIH proposes to establish a Rat Genome Database (RGDB). The objective of this RFA is to establish a database that will collect, consolidate, and integrate data generated from ongoing rat genetic, genomic, and related research efforts, and to make these data widely available to the scientific community. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Rat Genome Database , is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2000" at http://www.crisny.org/health/us/health7.html. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, companies, hospitals, laboratories, units of State and Local governments, and eligible agencies of the Federal Government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) R01 mechanism. The total project period for an application submitted in response to this RFA may not exceed 4 years. The anticipated award date is September 30, 1999. Although this RFA is a one-time solicitation, it is anticipated that there will be an ongoing need for a database effort to organize and relate rat data, and that funding for such a database effort will continue beyond the four years to be funded through this RFA. This RFA is an initiative of the Institutes listed above. However, the awards will be made by the National Heart, Lung, and Blood Institute (NHLBI) and will be managed by the NHLBI and the other participating Institutes. This grant may not be included in the Federal Demonstration Phase 3 or the Expanded Authorities. FUNDS AVAILABLE Approximately $1.7 million (including direct and facilities and administrative costs) is available for each year in the project period. It is anticipated that one award will be made. Proposed funding levels are subject to change due to budgetary, administrative, and/or scientific considerations. RESEARCH OBJECTIVES Background The rat is used extensively as a model organism for studying normal and disease processes in the human, primarily because of an extensive body of knowledge of rat physiological mechanisms, a significant number of rat models that mimic human diseases, the ease of breeding the rat, and the ability to generate inbred congenic and consomic rat strains. Once genes are identified in rats, pathophysiological mechanisms can be elucidated lending clues to the identification of human genetic counter-parts. Recognizing the usefulness of the rat as a model system, the NIH funded the Rat Genome Project and the Rat EST Project to develop genomic tools and resources. The genomic information and reagents developed through these efforts has grown at an astounding pace. Currently more than 6,000 "anonymous" genetic markers world-wide cover the rat genome and many hundreds of known genes are placed within this genetic framework. In addition to the genetic map, multiple large insert genomic libraries, radiation hybrid (RH) cell lines and a corresponding RH map, greater than 12 normalized cDNA libraries, allele characterization for nearly all genetic markers in 48 inbred strains of rats, a cytogenetic map, more than 50,000 ESTs with 2,000 of them RH mapped, and a developing rat/human/mouse syntenic map have all been generated. These resources have already served to enhance the power of the rat as a model system for identifying genes responsible for disease and health, defining gene function, understanding how genes interact with the environment, discovering and testing new drugs, and designing new prevention strategies. In addition to these genomic tools for studying the rat, emerging genetic technologies are now being applied to the rat. The production of transgenic rats is routine in many academic and commercial laboratories. These rats are being used to study hypertension and neoplasia, among other important public health problems. Collectively these genomic and genetic tools enable investigators to walk between rat and mouse and human using comparative mapping techniques, thereby providing an approach for discovery of gene function by linking physiology, genetics, and clinical phenotypes. The data and materials being developed by the Rat Genome and EST Projects are presently available through websites (http://www-genome.wi.mit.edu/ , http://brahma.mscs.mu.edu/BIOMATH/Research/ratgenome.html , http://www.informatics.jax.org/rat/). The advances in generating and utilizing new genomic tools for the rat has produced an increased demand for central accessibility of rat data to enhance access to the data and improve its correlation with the existing physiological and phenotypic information about the rat. Thus a centralized Rat Genome Database is needed to enable investigators from a large number of research areas and interests with a range of computer expertise to have access to the full range of information about the rat through one user interface. Furthermore, a centralized effort will provide the curation of rat data needed to provide links between genomic/genetic data and existing physiological and phenotypic data. This RFA calls for applications to establish and develop a comprehensive Rat Genome Database to meet the needs of the broad research community and to provide a foundation to enhance the use of the rat in discovering genes and understanding their functions. This resource will facilitate the translation of the wealth of previously published functional and phenotypic data from rat studies for integration with genetic and genomic data from the rat and other organisms, including the human and mouse. Objectives and Scope The primary goal of the Rat Genome Database will be to collect, consolidate, and integrate data generated from ongoing rat genetic and genomic research efforts and make these data widely available to the scientific community. A secondary but critical goal is to provide curation of mapped positions for quantitative trait loci, known mutations and other phenotypic data. It is recognized that the data encompassed by this latter goal are extensive and applicants must provide justification for their choice of data to be curated. The most responsive application will address the following elements: o A design based on rat biology: The philosophy and design of the RGDB should be derived from the biology of the organism, rather than the database technology that is available. The underlying organization of the database should enable investigators interested in utilizing rat genomic/genetic data to ask critical questions about the relation of that data to their field of interest whether it be in rat or another organism. However, the RGDB must recognize the hardware, software, and network capabilities of the research communities. o Curation: The RGDB should be curated by experts in the field to insure the high quality of the information and its correlation with other information about the rat. o Priorities: The RGDB must set clear priorities for data content, data capture, organization, curation, annotation, navigation, and presentation. o Utilization of existing database tools: Where possible, reuse or adaptation of existing software should be proposed to take advantage of the experience of others in the database field and to minimize expense. o Connection with rat research communities: A successful RGDB must have ties to the various rat biology communities. In addition, the RGDB must be able to support data inquiry from the broader scientific community. o An advisory board: An Advisory Board, representing scientists from the rat community, from other communities that use rat data, and with database expertise, should be established to provide advice and recommendations on a consistent and continuing basis to the RGDB, the research communities (specific and broad), and the NIH. o Database connections: The RGDB should establish and maintain effective cross-links between various model organism genomic/genetic databases, as well as with other types of databases. A more extensive discussion of model organism databases in general can be found in the NIH Model Organism Database Workshop Report. This Report may be obtained from the NHLBI (http://www.nhlbi.nih.gov/nhlbi/nhlbi.htm) and NHGRI (http://www.nhgri.nih.gov/) web sites or from Dr. Susan E. Old at the address listed under INQUIRIES. POST-AWARD MANAGEMENT During the course of the grant period, technologies will improve, methodologies will evolve, and the rate of progress and focus of work supported by the RGDB may change. It is expected that the Principal Investigator will make any necessary adjustment in scientific direction, in conjunction with the Advisory Committee and the NIH, to accommodate the changing environment. Annual Progress Reviews will be conducted by the NIH using outside advisors to provide guidance and oversight in order to ensure that the RGDB remains focused on appropriate goals, makes sufficient progress in achieving the elements listed in this RFA, and maintains flexibility to accommodate future scientific opportunities. Funds for these Progress Reviews, including travel for the progress review team, meeting space, etc., should be included in the application. These annual Progress Review meetings will take place either at the local institution or at the NIH. The site will be negotiated annually with the awardee. LETTER OF INTENT Prospective applicants are asked to submit, by than April 1, 1999, a letter of intent that includes a descriptive title, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows Institute staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to: C. James Scheirer, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7220, MSC 7924 Bethesda, MD 20892-7924 Telephone: (301) 435-0266 FAX: (301) 480-3460 Email: [email protected] APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. 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: [email protected]. The RFA label available in the PHS 398 (rev. 4/98) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. 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) At the time of submission, two additional copies of the application must also be sent to Dr. James Scheirer, as listed under LETTER OF INTENT. Applications must be received by April 26, 1999. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this announcement 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 substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NHLBI. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, CSR staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NHLBI in accordance with the review criteria stated below. As part of the initial merit review, a process will be used by the initial review group in which applications receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed, assigned a priority score, and receive a second level review by the NHLBI National Advisory Council. Review Criteria The goal of NIH-supported databases is to provide tools for use in advancing our understanding of biological systems, improving the control of disease, and enhancing 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 database 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. Note that the application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. (1) Significance: Does this database address the seven elements identified in this RFA? If the aims of the application are achieved, will scientific knowledge be advanced? Does this database provide value added data for the scientific communities? (2) Approach: Are the conceptual framework, design, methods, and products adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? (3) Innovation/Database Design: Where appropriate, does the project make the best use of existing software, database technology, and design? When necessary, does the project develop new methodologies or technologies? Where appropriate, does the project employ novel concepts, approaches or methods? (4) Investigator: Are the investigators 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)? Does the investigator or collaborators have an understanding of the needs of the rat scientific community and its relationship to the science of other communities? (5) Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed goals take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o The reasonableness of the proposed budget and duration in relation to the proposed research. o 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. Schedule Letter of Intent Receipt Date: April 1, 1999 Application Receipt Date: April 26, 1999 Peer Review Date: TBD Council Review: September 16-17, 1999 Earliest Anticipated Start Date: September 30, 1999 AWARD CRITERIA Factors that will be used to make award decisions are as follows: o Quality of the proposed project as determined by peer review, o Promise of the proposed program to accomplish the objectives listed in this RFA, o Availability of funds. INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Susan E. Old, Ph.D. Division of Heart and Vascular Diseases National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 9150 (MSC 7940) Bethesda, MD 20892-7940 Telephone: (301) 435-0477 FAX: (301) 480-1336 Email: [email protected] Thomas P. Jacobs, Ph.D. Division of Stroke, Trauma and Neurodegenerative Disorders National Institute of Neurological Disorders and Stroke 7750 Wisconsin Avenue, Room 8A13 Bethesda, MD 20892-9155 Telephone: (301) 496-4226 FAX: (301) 480-1080 Email: [email protected] Grace L. Shen, Ph.D., Cancer Genetics Branch National Cancer Institute 6130 Executive Boulevard, Room 501, MSC 7381 Rockville, MD 20892-7531 Telephone: (301) 496-7381 FAX: (301) 435-5226 Email: [email protected] Neal B. West, Ph.D. Comparative Medicine Area National Center for Research Resources 6705 Rockledge Drive, Room 6030 (MSC 7965) Bethesda, MD 20892-7965 Telephone: (301) 435-0744 FAX: (301) 480-3819 Email: [email protected] Lisa Brooks, Ph.D. Genome Informatics Program National Human Genome Research Institute 38 Library Drive, Room 614, MSC 6050 Bethesda, MD 20892-6050 Telephone: (301) 496-7531 FAX: (301) 480-2770 Email: [email protected] Robert Karp, Ph.D. Division of Basic Research National Institute on Alcohol Abuse and Alcoholism 6000 Executive Boulevard, Suite 402, MSC 7003 Bethesda, MD 20892-7003 Telephone: (301) 443-2239 FAX: (301) 594-0673 Email: [email protected] Steven L. Klein, Ph.D. Developmental Biology, Genetics and Teratology Branch National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 4B01, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 496-5541 FAX: (301) 402-4083 Email: [email protected] Eleni Kousvelari, Ph.D. Division of Extramural Research National Institute of Dental and Craniofacial Research Natcher Building, Room 4AN 18A Bethesda, MD 20892-6402 Telephone: (301) 594-2427 FAX: (301)480-8318 Email: [email protected] Catherine McKeon, Ph.D. Metabolic Diseases and Gene Therapy Research National Institute of Diabetes and Digestive and Kidney Diseases 45 Center Drive, Room 5AN.18B, MSC 6600 Bethesda, MD 20892-6600 Telephone: (301) 594-8810 FAX: (301) 480-3503 Email: [email protected] Theresa Lee, Ph.D. Division of Basic Research National Institute on Drug Abuse 5600 Fishers Lane, Rm. 10A-19 Rockville, MD 20857 Telephone: (301) 443-6300 FAX: (301) 594-6043 Email: [email protected] William A. Suk, Ph.D., M.P.H. Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, NC 27709 Telephone: (919) 541-0797 FAX: (919) 541-2843 Email: [email protected] Hemin Chin, Ph.D. Genetics Research Branch National Institute of Mental Health 5600 Fishers Lane, Room 10C-26 Rockville, MD 20857 Telephone: (301) 443-1706 FAX: (301) 443-9890 Email: [email protected] Direct inquiries regarding fiscal matters to: Ms. Jane Davis Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7174, MSC 7926 Bethesda, MD 20892-7926 Telephone: (301) 435-0166 FAX: (301) 480-3310 Email: [email protected] AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.837. 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. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant 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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