RFA-DK-00-002: NIDDK BIOTECHNOLOGY CENTERS

Department of Health
and Human Services (HHS)

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NIDDK BIOTECHNOLOGY CENTERS Release Date: September 23, 1999 RFA: DK-00-002 National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: January 14, 2000 Application Receipt Date: February 16, 2000 PURPOSE The purpose of this RFA is to make comprehensive gene expression technologies widely available to researchers working in areas supported by NIDDK. This RFA seeks to establish Biotechnology Centers that will provide genomic profiling resources to investigators working in research areas within the NIDDK"s mission. A companion RFA (DK-00-003) for small grants to supplement existing NIDDK grants to make gene profiling technology accessible on a project-by-project basis will also be issued. 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. Potential applicants may obtain a copy of "Healthy People 2000" at http://odphp.osophs.dhhs.gov/pubs/hp2000. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and nonprofit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for this solicitation. 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) resource-related (R24) grant mechanism award. Awards will be administered as stated in the NIH Grants Policy Statement. This RFA is a one-time solicitation. The total requested project period for an application submitted in response to this RFA may not exceed 3 years. The maximum dollar request is limited to $350,000 of direct costs for each budget year. All major equipment should be included in the first budget year. It is anticipated that the budget for years 2 and 3 will provide for pilot and feasibility studies of future projects using this technology. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The anticipated award date is September 30, 2000. FUNDS AVAILABLE For FY 2000, $4 million will be committed to fund applications submitted in response to this RFA. It is anticipated that about 8 Biotechnology Centers will be funded. However, this funding level is dependent upon the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NIDDK, the award of grants pursuant to this RFA is also contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES A. Background The tremendous acceleration in pace of scientific discovery over the last decade, coupled with development of many new high-throughput technologies, has created an era of unparalleled opportunity to uncover the causes of disease and identify effective therapies. In particular, the Human Genome Project and related efforts to identify at least some unique pieces of all expressed genes (expressed sequence tags, ESTs) in the human genome has resulted in an explosion of data and potential tools that will aid research in virtually all fields of medicine. The recent development of genome-wide expression profiling (chip, microarray or Serial Analysis of Gene Expression [SAGE] technologies) allows a comprehensive high-throughput screening of the effects of an insult (genetic, physiologic, pathologic, etc.) on gene expression in tissues and specific cell populations of interest. These techniques may aid in determining the function of a newly discovered gene or discovering new biomarkers and therapeutics for patients with disease. Many investigators with hypothesis-driven research programs want access to emerging technologies. Cost is a major obstacle to the application of these techniques by large numbers of investigators. The investment required to obtain essential equipment and personnel to establish this technology is more than can easily be borne by a single investigator. B. Objectives and Scope This RFA is intended to support the cost-effective introduction of techniques to measure patterns of gene expression in specific tissues of interest to the NIDDK-supported investigators. This RFA will allow the formation of support facilities that may include, but are not limited to: 1. cDNA Microarrays. The applicant might propose to print, read, and analyze microarrays. The arrays might contain mixtures of cDNAs obtained from commercial vendors, the Cancer Genome Anatomy Project (CGAP), or ESTs obtained locally and of specific interest to the investigators. It is anticipated that each printing unit will distribute arrays to 7 to 20 NIDDK investigators. Applicants are expected to identify the sources of the cDNAs, reference all genes to a genomic database (Entrez, Unigene, Locus Link, etc.), and indicate plans to distribute arrays to the NIDDK community at a reasonable cost. Applicants need not include budgets for equipment for printing or reading arrays or for bioinformatics support if they can obtain the necessary reagents or support from collaborative efforts or commercial sources. 2. Oligonucleotide chips. The applicant might propose to produce, hybridize, read, and/or analyze gene chips from commercial or academic sources. Applicants are expected to discuss the source and composition of the chips, and details of the bioinformatic support. 3. Serial Analysis of Gene Expression (SAGE). The applicant might propose to construct high quality cDNA libraries, link and sequence the SAGE tags, and analyze SAGE tags. Applicants are expected to discuss library quality, sequence fidelity, bioinformatic processing of SAGE tags, and statistical issues. Creation and maintenance of these technologies may require the collaboration of investigators with expertise in many fields, such as molecular biology, robotics, bioinformatics, genomics, and statistics. In addition, key aspects of infrastructure may also be supported and might include the development and maintenance of appropriate databases and specialized equipment. It is important to emphasize that there are a variety of approaches to genome-wide expression analysis. Therefore, a given strategy must be rigorously justified and must demonstrate that all key personnel are involved in the formulation of the rationale and approach. An objective of this RFA is to provide biotechnology support for both on-going and new hypothesis-driven research projects. Therefore, applicants will be required to describe projects that will benefit from these technologies. C. Annual Meetings The Principal Investigator must be willing to be part of a Steering Committee consisting of representatives of each Biotechnology Center. Annual meetings will be held to encourage exchange of information among investigators who participate in this program. A major goal of these meetings is to facilitate progress by providing a forum that will lead to sharing skills, ideas, technology, data, and biological reagents. At the meetings, participants will also discuss quality assurance, bioinformatics, coordination, and training. D. Sharing Data and Biological Materials in Human Genetic Research Timely sharing of information, materials, and technology will speed scientific discovery by permitting researchers access to sufficiently large and well-characterized resources as quickly as possible. This sharing of materials and data, including those that have not yet or may never be published, is essential to rapid progress and will help to avoid unnecessary duplication of large data collections. It is recognized that time may be required to verify the accuracy of data, to perform initial analyses, and to protect intellectual property rights to ensure that inventions, including therapeutic agents, are pursued and developed rapidly for the benefit of the public. Thus, a protected period, from the time data and materials are collected to the time they are made available to other qualified investigators, may be appropriate. The onset and duration of the period will vary, depending upon the nature of the research project. Applicants must justify the length of the protected period. Where appropriate, grantees may work with the private sector to make unique resources available to the larger biomedical research community at a reasonable cost. Applicants may request funds to defray the costs of sharing materials or submitting data, with adequate justification. Post-Award Management During the course of the grant period, technologies will improve, genomic technologies will evolve, and the rate of progress and focus of work supported by the grant(s) may change. It is expected that the Principal Investigator(s), after consultation with NIDDK program staff, will make any necessary adjustment in scientific direction to accommodate the changing environment. In order to ensure that the project(s) remains focused on appropriate goals, maintains excellent coordination with the other projects funded under this RFA, incorporates new technological advances and makes sufficient progress, scientific and programmatic visits to the grantees will be conducted at a frequency to be negotiated with the awardees. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which was published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide For Grants and Contracts, Vol. 23, No. 11, March 18, 1994, available on the web at: http://grants.nih.gov/grants/guide/notice-files/not94-100.html. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH 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 was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html. Investigators may also obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by January 14, 2000, a letter of intent that includes a descriptive title of the proposed research, 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 a subsequent application, the information that it contains allows NIDDK staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to: Chief, Review Branch Division of Extramural Activities, NIDDK Natcher Building, Room 6AS-37F 45 Center Drive MSC 6600 Bethesda, MD 20892-6600 Telephone: (301) 594-8885 FAX: (301) 480-3505 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 may be obtained 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 your 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. The sample RFA label available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to allow for this change. Please note this is in pdf format. 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 time of submission, two additional copies of the application must be sent to: Chief, Review Branch Division of Extramural Activities, NIDDK Natcher Building, Room 6AS-37F 45 Center Drive MSC 6600 Bethesda, MD 20892-6600 Applications must be received by February 16, 2000. If an application is received after that date, it will be returned to the applicant without review. Supplemental documents containing significant revision or additions will not be accepted, unless applicants are notified by the Scientific Review Administrator. 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 substantial revisions of applications previously reviewed, but such applications must include an introduction addressing the previous critique. Special Instructions to Applicants The applicants must carefully justify methodologies, technologies, bioinformatics, statistical analytical tools, and costs, and describe the limitations of the approaches. Genome-wide expression analysis is a rapidly evolving field. Hence, applicants must discuss how they will be poised to take advantage of technical and methodological advances and their impact on the throughput and costs proposed. Scientific Application to Hypothesis-Driven Research Projects: Applicants must include descriptions of 5 to 10 ongoing representative projects that will use the gene profiling technology. Applicants must also include descriptions of several pilot and feasibility studies for new projects that will use this technology. These projects should be proposed for budget years 2 and 3. The project descriptions should be short (0.5-1 pages each) and included in the Experimental Design and Methods portion of the application. The application must indicate how the projects will benefit from the new technology and how the results will be used in subsequent experiments. Training and Education: Currently, only a few NIDDK-supported investigators are in a position to use genomic technologies. To address this deficiency, each application must include plans to establish training and education programs. These programs should train local investigators to use these techniques. In addition, the applicants should indicate their willingness to provide service and training to the larger NIDDK community. The methods and procedures for selecting qualified individuals and the duration and types of service or training should be delineated in the application. Internal Advisory Committee: The application must describe the composition and functions of an internal advisory committee that would meet to discuss, for example, quality control, prioritization of resources, funding of pilot projects in years 2 and 3, training, sharing of reagents and experimental data, and adaptation to changing technologies. Annual Meetings: Applicants must include travel funds that will allow the Principal Investigator and at least one other key research scientist to participate each year for a one-day meeting in Bethesda, Maryland. Applications should include a statement indicating willingness to participate in these meetings. Sharing of Data and Biological Materials: In order to ensure the timely sharing of information and materials, applicants will be requested to describe in detail how, when, and in what manner data, materials, and technology will be made available to the scientific community. In addition, the applicant should outline how the rights and interests of the participants in genetic research will be assured. Applicants should discuss any pre-existing intellectual property rights, including options to for-profit research sponsors, who might be associated with the clones, sequences, and experimental results that may be generated. Applicants wishing to submit updated or supplementary material in support of their application can submit such material one time only no later than May 1, 2000. The submission is limited to two single-sided pages, and 20 copies of this should be submitted to Chief, Review Branch at the address below. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by NIDDK. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. 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 NIDDK in accordance with the review criteria stated below. As part of the initial merit review, all applications will receive a written critique and may 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 National Diabetes and Digestive and Kidney Diseases 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, reviewer 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. 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. o Significance: Do the scientific projects address important problems? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive the fields? o Approach: Will the technology resources significantly improve progress made by the projects. Are the conceptual framework, design, methods, and analysis adequately developed, well-integrated, and appropriate to the aims of the projects? Does the applicant acknowledge potential problem areas and consider alternative tactics? Are the applicant"s plans for quality control of all materials adequate? Is the bioinformatics support adequate? Is the applicant willing and able to participate actively in a collaborative program? Will the applicant share resources and release data in a timely manner, and will they train and educate other investigators in the use of these data and materials? o Innovation: Do the 5-10 representative projects employ novel concepts, approaches, or methods? Do the projects challenge existing paradigms or develop new methodologies or technologies? Are the 2-3 new pilot and feasibility studies innovative? o 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 investigators? o Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed technologies take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? The initial review group will also be asked to examine how the scientific projects will benefit from the new technologies, and how this will further NIDDK programmatic interests. In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o Adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. o The reasonableness of the proposed budget and duration to the proposed research. o The adequacy of the proposed protection of humans, animals, or the environment, to the extent that they may be adversely affected by the project proposed in the application. AWARD CRITERIA The anticipated date of award is September 30, 2000. Award criteria that will be used to make award decisions include: o Scientific merit as determined by peer review, o Availability of funds, o Programmatic priorities, including program relevance of the hypothesis-driven scientific projects that will be aided by the advanced technology, o Total cost of the project. 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: Robert A. Star, M.D. Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases 45 Center Drive MSC 6600 Bethesda, MD 20892-6600 Telephone: (301) 594-7715 FAX: (301) 480-3510 E-mail: [email protected] Philip F. Smith, Ph.D. Division of Diabetes, Endocrinology, and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases 45 Center Drive MSC 6600 Bethesda MD 20892-6600 Telephone: (301) 594-8816 FAX: (301) 480-3503 E-mail: [email protected] Jose Serrano, M.D., Ph.D. Division of Digestive Diseases and Nutrition National Institute of Diabetes and Digestive and Kidney Diseases 45 Center Dr MSC 6600 Bethesda MD 20892-6600 Telephone: (301) 594-8871 FAX: (301) 480-8300 E-mail:[email protected] Direct inquiries regarding fiscal and administrative matters to: Donna Huggins Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases 45 Center Drive MSC 6600 Bethesda, MD 20892-6600 Telephone: (301) 594-8848 FAX: 301-480-3504 E-mail: [email protected] AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.847, 93.848, and 93.849. 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 Parts 74 and 92. 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 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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