KOSEN 한인과학기술자네트워크

CENTERS OF EXCELLENCE IN GENOMIC SCIENCE - NIH Primary Sponsor: National Institutes of Health (Corporate-Wide) Deadline: 2/1/2001; 6/1/2001 KEYWORDS PA NUMBER: PAR-00-101 National Human Genome Research Institute Letter of Intent Receipt Dates: For Exploratory Grants (P20): May 1, September 1, January 1 annually For Specialized Center (P50): August 1, 2000; April 1 annually thereafter Application Receipt Dates: For Exploratory Grants (P20): June 1, October 1, February 1 annually For Specialized Center (P50): October 1, 2000; June 1 annually thereafter PURPOSE The National Human Genome Research Institute (NHGRI) is initiating a program to establish new academic Centers for advanced genome research. These Centers of Excellence in Genomic Science (CEGS) grants (P50) will support multi-investigator, interdisciplinary teams to develop innovative genomic approaches to address biological problems. The scope of the CEGS program is intended to be broad with a simple unifying theme that the Centers will address important biological problems on a "genomic scale." A CEGS may focus, for example, on a particular genome- scale biological problem, on the development of novel technological and computational methods for the production and analysis of comprehensive data sets, or on other ways to develop and use genomic approaches for understanding biological systems. In addition to pursuing research activities, a Center should help to nurture genomic science at its institution, for example, by facilitating the interaction of investigators from different disciplines and by providing training. The NHGRI particularly encourages the formation of new groups of investigators to conduct genomic research. As some newly formed groups may require substantial time and support for development and planning before being in a position to submit a high quality Center grant application, a CEGS Planning Grant (P20) is being offered to facilitate this planning. Applicants intending to focus their Center on bioinformatics approaches may also use the BISTI planning grant (available at: grants.nih.gov/grants/guide/pa-files/PAR-00-102.html) in preparation for the CEGS P50 Center grant application. RESEARCH OBJECTIVES Background The NHGRI is currently engaged, along with several other federal, private, and international organizations, in a multi-year research program called the Human Genome Project (HGP). Most of the initial goals of the HGP, including genetic and physical maps of the mouse and human, and the DNA sequences of E. coli, S. cerevisiae, C. elegans, and D. melanogaster have been realized. Others will be met imminently, including the complete human sequence. As of April 2000, more than three-quarters of the human sequence, either in finished or working draft form, has been deposited in the public sequence databases. After generation of a working draft version of at least 90% of the genome, completion of the high quality sequence will follow no later than 2003. Mouse genome sequencing has also begun, with completion of that sequence anticipated no later than 2005. The HGP has been characterized by a focus on large, comprehensive genomic data sets, such as complete DNA sequences and genomic maps, efficient data production, and the development of new technologies. Once the DNA sequence of an organism becomes available, many new avenues to studying its biology are opened. However, new and improved research tools, approaches, and capabilities are needed to discover and use the vast amount of biological information in complete genomic DNA sequences. In 1998, a set of new goals was adopted for the U.S. Human Genome Program (see Goals at www.nhgri.nih.gov/98plan/). In addition to completing the human and mouse maps and sequences, the aim of the HGP was extended to developing some of the new data sets and technological approaches that will be necessary to understand and use genomic DNA sequence. The purpose of this new solicitation is to stimulate the development of such new approaches, which are likely to involve computational, instrumental, biochemical, genetic, and analytical technologies. These approaches are likely to require the expertise of teams of investigators from different fields as well as substantial infrastructure. This Program Announcement (PA) signals an augmentation of the NHGRI Center grant program. Previous NHGRI solicitations for Center grants have had as their purpose the production of large data sets, such genetic maps, physical maps, or DNA sequences, and were derived from the quantitative resource- generation goals of the HGP five-year plans. While such programs continue, this new program is intended to provide support for novel basic genomics research projects. These new Centers will conduct research into biological problems at a genomic scale, or develop new methods, approaches, tools, or technologies to make possible novel analyses of biological questions from a genomic perspective. Some projects may result in new analyses of existing data sets. Other projects may result in technologies and methods that provide the ability to collect, analyze, and present effectively new types of genomic data sets. The NHGRI is committed to continuing to support basic genomic research through investigator-initiated, single-laboratory project grants, using the R01, R21, and other appropriate grant mechanisms, under existing and future programs. However, the resources needed to conduct the multi-faceted, multi-disciplinary projects that may be required to achieve significant advances in these complex problems are sometimes beyond the scope of the typical R01 grant. Therefore, this PA presents an opportunity for applicants to assemble the teams of investigators from diverse disciplines that will be required to approach biological problems using genomics tools in ways that are not possible today. High priority will be given to projects that integrate-investigator, multi- disciplinary approaches to a scientific problem, especially those that can meld computational and experimental approaches. Scope of Research The U.S. HGP goals for 1998-2003 (Science, Vol. 282, pp. 682-689, 23 Oct. 1998, see www.nhgri.nih.gov/98plan/) articulated several areas of genomics for which substantial research opportunities exist. The more recent publication of the Biomedical Information Science and Technology Initiative (BISTI) (www.nih.gov/welcome/director/060399.htm) lays out additional challenges, many of which are complementary to those of the HGP. The following excerpts from these reports exemplify the challenges and opportunities that lie ahead: o Sequencing Technology: "In the future, de novo sequencing of additional genomes, comparative sequencing of closely related genomes, and sequencing to assess variation within genomes will become increasingly indispensable tools for biological and medical research....[R]esearch must be supported on new technologies that will make even higher throughput DNA sequencing efficient, accurate, and cost-effective, thus providing the foundation for other advanced genomic analysis tools." (HGP goals) o Human Genome Sequence Variation: "Natural sequence variation is a fundamental property of all genomes....Basic information about the types, frequencies, and distribution of polymorphisms in the human genome and in human populations is critical for progress in human genetics. Better high- throughput methods for using such information in the study of human disease are also needed." (HGP goals) o Technology for Functional Genomics: "The availability of entire genome sequences is enabling a new approach to biology often called functional genomics - the interpretation of the function of DNA sequence on a genomic scale....Many genes and other functional elements of the genome are discovered only when the full DNA sequence is known....However, knowing the structure of a gene or other element is only part of the answer. The next step is to elucidate function, which results from the interaction of genomes with their environment....Large-scale characterization of the gene transcripts and their protein products underpins functional analysis....Improved technologies are [also] needed for global approaches to the study of non-protein-coding sequences...." (HGP goals) o Comparative Genomics: "Because all organisms are related through a common evolutionary tree, the study of one organism can provide valuable information about others. Much of the power of molecular genetics arises from the ability to isolate and understand genes from one species based on knowledge about related genes in another species. Comparisons between genomes...provide insight into the universality of biologic mechanisms and....into the details of gene structure and function." (HGP goals) o Bioinformatics and Computational Biology: "Bioinformatics support is essential to the implementation of genome projects and for public access to their output....Collection, analysis, annotation, and storage of the ever increasing amounts of mapping, sequencing, and expression data in publicly accessible, user-friendly databases is critical to the project's success. In addition, the community needs computational methods that will allow scientists to extract, view, annotate, and analyze genomic information efficiently." (HGP goals) o "To make optimal use of information technology, biomedical researchers need, first of all, the expertise to marry information technology to biology in a productive way. New hardware and software will be needed, together with deepened support and collaboration from experts in allied fields. Inevitably, those needs will grow as biology moves increasingly from a bench-based to a computer-based science, as models replace some experiments and complement others, as lone researchers are supplemented by interdisciplinary teams. The overarching need is for an intellectual fusion of biomedicine and information technology." (BISTI goals) o "The information that biomedical researchers are amassing in profuse quantities today...creates enormous digital repositories of information. The scale of those databases swamps all the information collected before....In order to be useful, the data must be indexed and stored, and the challenges for data analysis and abstraction are formidable." (BISTI goals) The passages quoted above from the U.S. HGP five-year plan and the BISTI report are intended to convey the kinds of subjects and scope of projects that may be appropriate under this Centers program. This PA does not provide a list of examples of possible Center themes because of the NHGRI's desire not to limit applicants imaginations and to solicit truly new ideas for genomic approaches to biological problems, related to the goals discussed above. The NHGRI strongly encourages investigators who propose to develop such novel approaches to discuss their ideas with NHGRI program staff prior to submitting an application, to ensure that applications will be responsive to the CEGS program. Biomedical research has entered an era in which the solutions to many important problems will require the collection and analysis of large data sets, such as an entire genome, an entire set of expressed RNAs or proteins, an entire gene family from a large number of species, the variation among individuals for a genomic region of substantial size, or a class of gene regulatory or chromatin organizational elements. Therefore, the unifying theme for this program will be that the Centers will address important biological problems on a "genomic scale." Preference will be given to approaches and technologies that are applicable to a wide variety of cell types or organisms and that are usable in a high-throughput, cost-effective, comprehensive manner, i.e., are "genomic technologies." Similarly, preference will be given to approaches designed to be generally applicable at large scale, for example, not limited to any one genetic locus, specific disease, or organ system. Preference will be given to the development of genomic methods for eukaryotes where genome sequence is available. Methods development or pilot studies using other systems (e.g., eukaryotes whose genomes have not been sequenced, or prokaryotes for which the genomic sequence is known) will be considered with adequate justification; direct applicability to the analysis of eukaryotic genomes must be evident. Where appropriate, integration with other NIH genomics initiatives (e.g., NHLBI genomics program [grants.nih.gov/grants/guide/rfa-files/RFA-HL-99-024.html], full-length cDNA [www.ncbi.nlm.nih.gov/MGC/], and SNPs [www.nhgri.nih.gov:80/About_NHGRI/Der/SNPawardees.htm]) will be considered advantageous. It is anticipated that these Centers may employ large amounts of data to accomplish their goals. However, the application of genomic technologies for data production per se is not the purpose of these Centers. Instead, these Centers may generate data sets to address a biological problem, or may develop tools. The generation of test data sets may be appropriate for developing the methods and technologies, or demonstrating the feasibility of methods under investigation. The cost- effectiveness of the project plan will be a review criterion. Decisions by NHGRI to embark on the large-scale implementation of any new tools developed by these Centers to generate large data sets, particularly when such projects are expensive, will require careful consideration, with advice from the scientific community. INQUIRIES Inquiries are strongly encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Jeffery A. Schloss, Ph.D., Division of Extramural Research, National Human Genome Research Institute, NIH Bldg. 31, Room B2-B07 Bethesda, MD 20892-2033 TEL: (301) 496-7531 FAX: (301) 480-2770 Email: jeff_schloss@nih.gov. Direct inquiries regarding review issues to: Scientific Review Branch, National Human Genome Research Institute, NIH Bldg. 31, Room B2-B37 Bethesda, MD 20892-2032 TEL: (301) 402-0838 FAX: (301) 435-1580 Direct inquiries regarding fiscal matters to: Jean Cahill Grants Administration Branch National Human Genome Research Institute, NIH Bldg. 31, Room B2-B34 Bethesda, MD 20892-2031 TEL: (301) 402-0733 FAX: (301) 402-1951 E-mail: jc166o@nih.gov.