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Genome, Structural Biology, And Related Biotechnologies

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(SBIR) DOE - Genome, Structural Biology, And Related Biotechnologies Primary Sponsor: Department of Energy Deadline: 2/20/2001 KEYWORDS a. Genomic Analysis Technologies b. DNA Mapping Methods for Chromosome Analysis c. Gene Products and Interactions d. Informatics Support of Functional Analysis The Department of Energy (DOE) supports research to acquire a fundamental understanding of biological and environmental processes. This research includes the characterization of genomes and gene products from humans and other organisms; structural biology research using beamlines at synchrotron sources and other facilities; as well as studies in computational structural biology, computational genomics, and biological information systems. Knowledge gained in this research is used to exploit genomic information, determine the structure of biological macromolecules, integrate advances in computational and mathematical sciences into biology, understand protein folding mechanisms, and clarify the relationships between genes, gene product structures, and biological function. Such knowledge should enable the public and private sector to: (1) markedly improve human health care and promote worker and public safety; (2) promote application of DNA-based biotechnology to environmental applications, like bioremediation; (3) facilitate the isolation, characterization, and treatment of factors involved in human diseases and disorders; and (4) promote cleaner industrial processes using biotechnology. Close interactions with one of the DOE laboratories or projects can be beneficial in the development of a grant application. Grant applications are sought only in the following subtopics: a. Genomic Analysis Technologies¾Several genomic analysis resources and technologies, initially developed under basic research grants, have now matured to the point where commercialization has become a distinct possibility. Grant applications are sought to further develop one or more of the following technologies, leading to kits or services that could be offered for sale: (1) clone libraries derived from single copy vectors, such as BACs (bacterial artificial chromosomes) and fosmids; (2) probe reagents supporting fractionation of the genome into chromosomal components; (3) economical kits of STS primer pairs, to support analyses of "gene families" across populations. b. DNA Mapping Methods for Chromosome Analysis¾The annotation of genomes and/or chromosomes with sequence based markers is useful for clarifying the chromosomal constituents of a species, intrachromosomal structure analysis, and quality control of the algorithmic assembly processes of DNA sequencing. DNA optical mapping and DNA fibre FISH (fluorescence in situ hybridization) are technologies that support this annotation at kilobase resolutions, while retaining long range DNA continuity information. Grant applications are sought to further develop these technologies, leading to mapping services for them and their eventual transfer to interested customers. In addition, applications for novel technologies (in addition to DNA optical mapping and DNA fibre FISH) that would achieve the same objectives will also be considered. Constituents of interest include biochemical, instrumentation, and computational analyses. c. Gene Products and Interactions¾Production methods for making dense arrays of oligomers and nucleic acids are well established for analytic and diagnostic readouts. However, a need remains for the development of comparable protein arraying technologies. These technologies can potentially be used in massively parallel tests of bio-activity, monitoring metabolic status, biochemical processes, and/or exposure to external materials. To address this need, grant applications are sought to develop: (1) microarrays of uncharacterized gene products (for functional analysis); (2) microarrays of gene products to assess interactions with other biomolecules (including nucleic acids); or (3) microarrays of gene products to assess physiological states. Grant applications should include a discussion of how the output signals or data will be processed, so that these microarray technologies, if successful, could potentially be incorporated into automated systems. d. Informatics Support of Functional Analysis¾The draft human genome will mature into a highly finished sequence over the next two years. An increasing number of genomes of model organisms and microbes are also being displayed as DNA sequence of chromosomes. Computational support for the functional analysis of these immense information resources is of increasing importance. Grant applications are sought to further develop software and computation tools for the processing and analyzing of genome scale information resources and large sub-families thereof. Grant applications must demonstrate that the tools will lead to services that will aid users who are non-specialists in computer sciences and that the services will be complementary to, rather than directly competitive with, public and private sector services already well established. Please note: (1) The technical topics are to be interpreted literally; DOE personnel are not permitted to further interpret the narrative description of the technical topics. (2) The award selection process is extremely competitive. Last year, only 1 out of 6 grant applications were awarded. Only those applications with the highest scientific/technical quality will be competitive. References Adams, M. D., et al., "A Model for High-Throughput Automated DNA Sequencing and Analysis Core Facilities," Nature, 368(6470):474-475, March 31, 1994. (ISSN: 0028-0836)Argos, P., "Sensitive Methods for Determining the Relatedness of Proteins with Limited Sequence Homology," Current Opinion in Biotechnology, 5(4):361-371, August 1994. (ISSN: 0958-1669)Bork, P., et al., "From Genome Sequences to Protein Function," Current Opinion in Structural Biology, 4(3):393-403, June 1994. (ISSN: 0959-440X)Bult, C. J., et al., "Complete Genome Sequence of the Methanogenic Archaeon, Methanococcus Jannaschii," Science, 273(5278):1058-1073, August 23, 1996. (ISSN: 0036-8075)Cai, W., et al., "Ordered Restriction Endonuclease Maps of Yeast Artificial Chromosomes Created by Optical Mapping on Surfaces," Proceedings of the National Academy of Sciences of the United States of America, 92(11):5164-5168, May 23, 1995. (ISSN: 0027-8424)Duell, T., "A Construction of Two Near-Kilobase Resolution Restriction Maps of the 5' Regulatory Region of the Human Apolipoprotein B Gene by Quantitative DNA Fiber Mapping (QDFM)," Cytogenetics and Cell Genetics, 79(1-2):64-70, 1997. (ISSN: 0301-0171)Heiskanen, M., et al., "A Fiber-FISH: Experiences and a Refined Protocol," Genetic Analysis: Techniques and Applications, 12(5-6):179-84, March 1996. (ISSN: 1050-3862)Johnson, M. S., et al., "Knowledge-Based Protein Modeling," Critical Reviews in Biochemistry and Molecular Biology, 29(i1):1-68, 1994. (ISSN: 1040-9238)Jones, D. T., "Theoretical Approaches to Designing Novel Sequences to Fit a Given Fold," Current Opinion in Biotechnology, 6(4):452-459, August 1995. (ISSN: 0958-1669)Rosenberg C., et al., "High Resolution DNA Fiber-Fish on Yeast Artificial Chromosomes: Direct Visualization of DNA Replication," Nature Genetics, 10(4):477-479, August 1995. (See also: Collins, F. S., "Positional Cloning Moves from Perditional to Traditional," Nature Genetics, 11(1):104, September 1995) (ISSN: 1061-4036)Rowen, L., et al., "The Complete 685-Kilobase DNA Sequence of the Human Beta T-Cell Receptor Locus," Science, 272(5269):1755-1762, June 21, 1996. (ISSN: 0036-8075)Sali, A., "Modeling Mutations and Homologous Proteins," Current Opinion in Biotechnology, 6(4):437-451, August 1995. (ISSN: 0958-1669)Uberbacher, E., "ORNL Announces GenQuest and X-GRAIL," Human Genome News, 5(5):8-9, January 1994. (Available from Human Genome Management Information System, Oak Ridge National Laboratory, 1060 Commerce Park, MS-6480, Oak Ridge, TN 37831. Telephone: 423-576-6669) World Wide Web Information 1. BAC (Bacterial Artificial Chromosomes) related sites: a. End Sequencing (1) University of Washington Department of Molecular Biotechnology http://www.mbt.washington.edu/ (2) The Institute for Genomic Research http://www.tigr.org b. History - Sequence Tag Connectors Production on Human BACs http://www.ornl.gov/meetings/bacpac/index.html c. National Center for Biotechnology Information http://www.ncbi.nlm.nih.gov d. Production (1) Caltech Genome Research Laboratory (2) Roswell Park Cancer Institute BACPAC Resource Center http://bacpac.med.buffalo.edu/ e. Protein Data Bank of the Research Collaboratory for Structural Bioinformatics http://www.pdb.bnl.gov/ f. U.S. DOE Office of Biological and Environmental Research http://www.er.doe.gov/production/ober/ober_top.html 2. Fibre FISH (Fluorescence In Situ Hybridization) http://www-hgc.lbl.gov/instr/weier.html 3. Human Genome Project Information 4. Nucleic Acid Database of Rutgers University 5. Optical Mapping NOTE: The Solicitations listed on this site are copies from the various SBIR agency solicitations and are not necessarily the latest and most up-to-date. For this reason, you should always use the suggested link below. This will take you directly to the appropriate agency information where you can read the official version of the solicitation you are interested in. The official link for this page is: http://sbir.er.doe.gov/sbir/Solicitations/FY%202001/2001.htm. Solicitation closing date is February 20, 2001.