JP2@CU.NIH.GOV (01/10/90)
Following is the Human Genome Program Announcement for research grants (RO1), Program Projects (PO1), FIRST awards (R29) Resouces related projects and biotechnology resource grants (R24, and P41), Research Career Development Awards (K04), Conference Grants (R13), and Small Business Innovation Research grants (SBIR, R43 and R44). Pilot projects may be submitted under the RO1 program. TECHNOLOGY DEVELOPMENT, MAPPING, AND DNA SEQUENCING IN SUPPORT OF THE HUMAN GENOME PROGRAM P.T. 34; K.W. 1215018, 0755045, 1002058, 1004017, 1003012, 1002008, 0710030 Office of Human Genome Research This Program Announcement restates the interest of the National Institutes of Health (NIH) in receiving research grant applications for studies related to the Human Genome Initiative. The present announcement supersedes the previous NIH-wide Program Announcement (November 4, 1988) on mapping and determining the DNA sequence of the genomes of the human or of model organisms. The objective is to stimulate creative, innovative research that will substantially improve the rapidity, efficiency and accuracy with which mapping and DNA sequence data can be obtained, analyzed, and distributed. Vol. 18, No. 26, July 28, 1989 - Page 3 BACKGROUND INFORMATION The NIH is currently engaged, along with several other federal, private, and international organizations, in a research program known as the Human Genome Initiative. This program is designed to characterize the human genome and the genomes of selected model organisms. It has several interrelated goals: the construction of high resolution genetic linkage maps; the development of a variety of physical maps; the determination of the complete nucleotide sequence of the DNA of selected organisms; the development of the capability for collecting, storing, distributing, and analyzing the data and materials produced; and the development of appropriate new technologies necessary to achieve these objectives. The information that will be obtained within the genome project will be a resource for studies of gene structure and function and will promote research into the genetic aspects of human disease. In this way, the Human Genome Initiative will serve as an underlying source of information for, and stimulus to, a wide range of studies from the most basic to targeted and clinical programs across the spectrum of NIH interests and responsibilities. In the past two years, several announcements/solicitations for grant applications related to the Human Genome Initiative have been published in the NIH Guide for Grants and Contracts. These include two broad Program Announcements and several Requests for Applications. This Program Announcement consolidates the prior announcements/solicitations in one document and emphasizes the continuing, ongoing interest on the part of the NIH in receiving grant applications for support of research projects that address the goals of the genome program with a wide range of research activities. One area in which research activities are encouraged is the development of improved technology for physical mapping, for the determination of DNA sequences, and for the management of the information that accrues. A separate, but equally important, area includes research projects that seek to increase the information available about specific genomic regions through the expansion of genetic maps, the construction of physical maps, or pilot projects for large-scale DNA sequence determination. Creative, novel approaches in all these areas will be essential to the success of the genome project. To this end, the NIH encourages interdisciplinary programs that draw from fields such as information science, chemistry, physics, and engineering, in addition to the biological sciences. Progress will be accelerated by cooperation and interaction among investigators. Therefore, it is expected that all materials and information derived from this work will be made available to the scientific community in a timely manner, in accord with Public Health Service policy. Within the genome program, awardees will be expected to share information and to work closely with other laboratories involved in related projects. RESEARCH SCOPE This Program Announcement is intended to emphasize the ongoing commitment of the NIH to the specific goals of the genome project and to the development of methodological tools and resources which would support this effort, including the storage and retrieval of materials and data. Applications responsive to this announcement will include a broad spectrum of research approaches to genetic and physical mapping, DNA sequencing, data handling and new methods of data interpretation. Development of new and imaginative technologies needed to support the genome project are especially encouraged. The topics described below are not intended to limit the types of applications that are acceptable in response to this announcement, but rather to illustrate the range of work that will be needed to attain the goals of the genome project. However, research directed toward analysis of the biological function of specific genes or gene systems, or the application of genetic information to the understanding, diagnosis, prevention, or treatment of specific genetic disorders is not within the scope of the genome program. Such work is currently supported by a number of other programs at the NIH. Information about these programs can be obtained from individual Institutes. Potential applicants are encouraged to contact one of the representatives listed below to discuss the proposed research project and for additional information. Technology Development The objective is to stimulate creative, innovative research that will lead to substantial improvements in the speed, efficiency and accuracy with which mapping and DNA sequence data can be obtained, analyzed, and distributed. Such improvements can be achieved through automation of existing methodology, development of new approaches, or both. Multi-disciplinary approaches to the Vol. 18, No. 26, July 28, 1989 - Page 4 attainment of these goals are encouraged. Examples of the problems for which improved technological solutions and/or automation are needed are: o generating, purifying, and cloning large DNA fragments; o constructing physical maps, including long-range restriction maps and overlapping sets (contigs) of DNA fragments that are derived from specific chromosomal regions and are connected into more extensive physical arrays; o determining relationships between genetic and physical maps; o locating specific genes on genetic and physical maps and within regions of sequenced DNA; o determining DNA sequence, including assembling overlapping DNA sequences into longer arrays; o storing, analyzing, and distributing the data obtained in each of these activities; and o storing and distributing the materials generated by all of these activities. Applicants are advised to take several general considerations into account when designing new projects. o Methodological improvements have played an important role in advancing biological research, never more so than in the past twenty years. In general, when technology development has been successful, it has been driven by the desire to solve specific scientific problems. Therefore, it is reasonable to expect that, within the context of the genome program also, the most successful new technologies will come from those endeavors in which the attempt to develop better technology occurs in the context of a specific research problem related to genomic analysis. Applicants are encouraged to clearly define the biological problem for which the technological solution is being devised. Applicants whose expertise is primarily non-biological and who are interested in addressing problems of genome analysis with new, non-biological tools are especially encouraged to interact closely with biologists. o It has been suggested that to significantly increase the rate at which mapping and sequence data can be acquired, efforts should be directed toward improving by three- to five-fold the scale and/or efficiency with which particular steps in mapping, sequence determination, or data analysis can be accomplished. Such an incremental increase can serve as a useful benchmark in designing a research program. o Achievement of such a significant improvement in analytical capability may require entirely new approaches. Methods that have been useful for addressing particular needs in the past, such as determining the sequence of a few kilobases of DNA, may not be adequate for addressing comparable problems on a much larger scale. The NIH recognizes that novel approaches may involve a considerable degree of risk and encourages submission of high-risk, high pay-off projects in response to this announcement. Mapping and DNA Sequencing The objective is to increase our knowledge of the genetic and physical maps and the DNA sequence of selected organisms, leading up to the complete maps of the human genome and the complete human DNA sequence. Research projects in the following areas are encouraged: o expanding the genetic map of the human, or of those model organisms for which such information would serve to promote the objectives of the overall genome program; o constructing physical maps of the chromosomes of the human and of model organisms, including projects for large-scale physical mapping; and o pilot projects for large-scale DNA sequence determination, involving the DNA of model organisms or regions of the human genome. Vol. 18, No. 26, July 28, 1989 - Page 5 The primary goal of research projects proposed under this section will be the generation of a substantial amount of new mapping and/or sequence information. The project may utilize current technology or propose new or improved technology. If current technology is used, it should be used at or near its limits in order to explore its capabilities. Because of the extensive amount of information already available about the genetics and molecular biology of E. coli, S. cerevisiae, D. melanogaster, C. elegans, and M. musculus, the genome program is particularly interested in promoting study of these models. However, research projects that involve other models are also expected to make important contributions to the Human Genome Initiative by means of both development of new technology and improved understanding of genome structure through comparative studies. Thus, no model organism is excluded from the genome program a priori. However, applicants proposing to study models other than those named above must provide a rationale, in terms of the goals of the overall genome program, for the use of such another model. MECHANISMS OF SUPPORT Support for this program will be through research grants, including project grants (R01), program project grants (P01), FIRST awards (R29), resources related research projects and biotechnology resource grants (R24, P41), Research Career Development Awards (K04), conference grants (R13) and Small Business Innovation Research (SBIR) grants (R43, R44). Because not all institutes support all of the above mechanisms, potential applicants are encouraged to contact the representatives listed below for additional information. Policies that govern research grant programs of the NIH apply to this program. Consortium arrangements and collaborative projects among scientists with skills in biological sciences, chemistry, physics, information science, and engineering are encouraged. APPLICATION AND REVIEW PROCEDURES Applications in response to this announcement will be reviewed in accordance with the usual NIH peer review procedures. They will first be reviewed for scientific and technical merit by a special study section in the Division of Research Grants organized for this purpose. Following the initial review, the applications will be considered by the appropriate National Advisory Board or Council. Review criteria that will be used to assess the scientific merit of an application are the following: o Scientific merit; o Potential value of the research for furthering the goals of the genome project; o Feasibility of the research and adequacy of the experimental design; o Significance and originality of the research and methodological approaches, as they relate to the genome project; o Training, experience, research competence, and dedication of the investigator(s); o Adequacy of available facilities; o Provisions for the protection of human subjects, the humane care of animals, and biosafety conditions; o Appropriateness of the requested budget for the work proposed. Because the significance of the proposed research project to the goals of the Human Genome Initiative is a criterion for review, consultants must consider this aspect in the evaluation of an application submitted in response to this Program Announcement. Applicants are, therefore, encouraged to consult with one of the staff listed below before submission, to discuss the relevance of a proposed application to the genome program. METHOD OF APPLYING Applications should be submitted on Form PHS 398 (rev. 10/88). Application kits are available in most institutional business offices and from the Office of Grants Inquiries, Division of Research Grants, Westwood Building, Room 449, National Institutes of Health, Bethesda, Maryland 20892; telephone (301) 496-7441. Vol. 18, No. 26, July 28, 1989 - Page 6 Applications will be accepted in accordance with the usual NIH receipt dates that apply for the various mechanisms listed under MECHANISMS OF SUPPORT. It is essential that applicants type "Technology Development, Mapping, and DNA Sequence Determination in Support of the Human Genome Initiative" in item 2 on the face page of the application form. The original and six copies of the application should be submitted to the following office: Application Receipt Office Division of Research Grants Westwood Building, Room 240 National Institutes of Health Bethesda, Maryland 20892** Telephone: (301) 496-7273 The conventional presentation for grant applications should be utilized. Funding decisions will be based on recommendations of the initial review group and of the National Advisory Council regarding scientific merit and program relevance, as well as on the availability of funds. INQUIRES It is strongly recommended, but not required, that potential applicants contact the Office of Human Genome Research (OHGR) or the staff member at the appropriate NIH institute to discuss research objectives. BID CONTACT BUILDING ROOM TELEPHONE OHGR Bettie Graham, Ph.D. Shannon 201 496-0844 NIDDK Robert Katz, Ph.D. Westwood 607 496-7997 NCI Cheryl Marks, Ph.D. Executive 630 496-7028 Plaza South FIC Lynn Amende, Ph.D. 38A 613 496-6688 DRR Charles Coulter, Ph.D. Westwood 8A11 496-5411 NIA Huber R. Warner, Ph.D. 31 5B39 496-6402 NICHD Delbert Dayton, M.D. Executive 5C19 496-5541 Plaza North NINDS N.C. Myrianthopoulos, Ph.D. Federal 8C04 496-5821 NLM Arthur Broering, Ph.D. 38A 8C16 496-4621 NIDR John Townsley, Ph.D. Westwood 506 496-7807 NIGMS Irene Eckstrand, Ph.D. Westwood 920 496-7137 NIAMS Steven Hausman, Ph.D. Westwood 403 496-7495 NHLBI Carol Letendre, Ph.D. Federal 506 496-6402 NIAID William Duncan, Ph.D. Westwood 754 496-5598 NEI Jack McLaughin, Ph.D. 31 6A08 496-9110 Mailing address for the above offices: Bethesda, Maryland 20892 All Bethesda telephone numbers are in area code 301. **THE MAILING ADDRESS GIVEN FOR SENDING APPLICATIONS TO THE DIVISION OF RESEARCH GRANTS OR CONTACTING PROGRAM STAFF IN THE WESTWOOD BUILDING IS THE CENTRAL MAILING ADDRESS FOR THE NATIONAL INSTITUTES OF HEALTH. APPLICANTS WHO USE EXPRESS MAIL OR A COURIER SERVICE ARE ADVISED TO FOLLOW THE CARRIER'S REQUIREMENTS FOR SHOWING A STREET ADDRESS. THE ADDRESS FOR THE WESTWOOD BUILDING IS: 5333 Westbard Avenue Bethesda, Maryland 20816