48. GENOMES-TO-LIFE (GTL) AND RELATED BIOTECHNOLOGIES
The Department of Energy (DOE) supports research to acquire a fundamental understanding of biological and environmental processes. This includes the display of genomes as DNA sequences; the functional characterization of gene products, especially from DOE-relevant plants and microbes; structural biology user stations at synchrotron sources and neutron sources; computational genomics; and the development of integrated information systems. This topic is focused on the goals of the Genomes to Life (GTL) program: namely, to develop a detailed understanding of the molecular machines of DOE-relevant microbes and their networking in living cells and microbial communities. Microbes with capabilities that can further several DOE programmatic missions are being used as the current subjects for these studies. The genome knowledge thus gained is enabling both the public and private sectors to: apply genome knowledge to the bio-production of energy, promote environmental applications such as bioremediation and carbon sequestration, promote cleaner industrial processes, and enable increasingly effective computational models of the microbial cell. For some of the subtopics below, capabilities already exist in a few laboratories, but commercial involvement will be needed before the technology can be exported to the broader research community. Grant applications are sought only in the following subtopics:
a. Innovative Protein Production Technology in Microbes and Plants—A number of proteomics tasks are being pursued to achieve the goals of the GTL program. These tasks include high-throughput production and purification of proteins, correlation of proteins with the genes encoding their primary structure, identification of protein isoforms encoded by the same gene, identification of memberships in functional complexes of proteins, and identification of the variations of proteome constituents under change to useful physiological states. However, a number of obstacles hinder the efficient accomplishment of these tasks. For example, several host-vector systems are available for the production of proteins encoded in a hyper-expressed source gene; yet, for some source genes, the proteins fail to fold into physiologically effective three-dimensional conformations (entrapment in insoluble inclusion bodies is one cause of such failures). Another difficulty is that proteins targeted to membranes are difficult to produce and isolate. Lastly, the lack of affinity reagents, which bind to proteins in their native conformations, adversely impacts structure, protein association, and function analyses. Therefore, grant applications are sought for the improved recovery and analysis of effective proteins. Areas of interest include: (1) the production of solubilized membrane proteins in active conformations, with or without post-translational modifications; (2) the development of synthetic membranes or nano-structures enabling analyses of membrane proteins; (3) and the development of improved affinity reagents.
Questions - contact Marvin Stodolsky (marvin.stodolsky@science.doe.gov)
b. Improved Technology for Transformation of Plant Cells—The genetic engineering of microbes for beneficial purposes is now routine, with robust technologies available for gene transformation and mutagenesis. For plants, comparable precision engineering capabilities are not yet available; however, these capabilities are essential for enhancing our fundamental understanding of gene function and regulation, especially with respect to production of significant amounts of biofuels. Grant applications are sought to develop innovative methods in plant improvement and biotechnology, in order to: (1) improve the efficiency and fidelity of: chromosomal homologous recombination, chromosomal gene targeting, and high-throughput stable transformation and phenotyping of emerging biomass crops (especially perennial grasses); and (2) introduce and establish new chromosomes carrying desirable gene(s) in plants.
Questions - contact Marvin Stodolsky (marvin.stodolsky@science.doe.gov)
c. Microbe-Based Fuel Production—Biotechnology offers the promise of capitalizing on the natural capabilities found in the microbial world to produce new fuels, leading to a reduction in green house gas emissions. In particular, many microbes have the ability to produce hydrogen under particular conditions. Therefore, grant applications are sought to demonstrate and quantify: (1) microbe-based hydrogen production reactors, or (2) high-throughput assays for assessing and quantifying the production of microbe-based hydrogen in experimental reactors.
In addition, a more complete understanding of the enzymes and microbes involved in the conversion of cellulosic material to ethanol could overcome inefficiencies in current production processes. Therefore, grant applications are sought to take advantage of advances in GTL science, as well as in systems biology, to simplify and consolidate the conversion of cellulose to ethanol. Emphasis should be placed on developing process improvements from externally generated, biologically-derived catalysts; single organisms; and/or integrated microbial systems composed of a stable consortium of organisms. Approaches of interest include improving the pretreatment of lignocellulosic material for saccharification and developing organisms that: (1) thrive in optimal bioreactor temperatures and pH environments; (2) ferment both C5 and C6 sugars; and (3) catalyze products in spite of inhibitors, including high concentrations of ethanol. Proposed approaches should coordinate with the research goals described in the DOE GTL Roadmap [7] and Breaking the Biological Barriers to Cellulosic Ethanol: a joint research agenda [8].
Questions - contact Marvin Stodolsky (marvin.stodolsky@science.doe.gov)
d. Informatics—Scientists studying the microbiology of environmental applications need to address a wide variety of data that should be linked to each other and readily accessible to multiple members of a team. These data arise from many sources, both from team members and from the broader research community. Grant applications are sought to develop a user-friendly, visual database interface that can display biological data that is applicable in both a laboratory context (i.e., data describing samples that are tracked by a LIMS-type application) and a biological context (i.e., data that provides inference across organisms). The database interface should be interoperable across different locations. The software should be capable of combining environmental, phenotypic, and genomic data for microbes, along with image and biochemistry data – all keyed where appropriate to geographic data. The phenotypic data should include information such as growth curves and metabolic capabilities; the genomic data should include arrays, proteomics, and metabolomics; the image data should include both in situ and labeled data; and the biochemistry data should include information such as activities and localization of enzymes. Grant applications must demonstrate that the needs of biological research teams will be addressed. The resultant software package should be available at modest cost, so that it is accessible to typical biological research teams.
Questions - contact Marvin Stodolsky
(marvin.stodolsky@science.doe.gov)
References:
1.
U.S. DOE GTL Bioenergy Research Center Competition:
News release:
http://www.doe.gov/news/3872.htm
Details:
http://www.grants.gov/search/search.do?oppId=10474&mode=VIEW
2. “Breaking the Biological Barriers to Cellulosic Ethanol: A Joint Research Agenda,” U.S. DOE Office of Science and Office of Energy Efficiency and Renewable Energy, June 2006. (Report No. DOE/SC/EE-0095) (Available at: http://www.doegenomestolife.org/biofuels/)
3. “Genomics:GTL Roadmap,” Systems Biology for Energy and Environment Website, U.S. DOE Office of Science, August 2005. (URL: http://doegenomestolife.org/roadmap/index.shtml)
4. Year 2006 DOE SBIR Awards in the Genomes To Life (GTL) Program, within http://www.science.doe.gov/sbir/awards_abstracts/sbirsttr/cycle24/phase1/p1_award.htm. Scroll down to awards in 8th topic: GENOMES TO LIFE AND RELATED BIOTECHNOLOGIES within http://www.science.doe.gov/sbir/awards_abstracts/sbirsttr/cycle23/phase2/p2_award.htm. Scroll down to awards in 5th topic: GENOMICS: GENOMES TO LIFE AND RELATED BIOTECHNOLOGIES
5. DOE Joint Genome Institute Website, U.S. DOE Office of Biological and Environmental Research (OBER). (URL: http://www.jgi.doe.gov)
6. Genomics:GTL—Systems Biology for Energy and Environment Website, U.S. DOE OBER/Office of Advanced Scientific Computing Research. (URL: http://doegenomestolife.org/)
7. Research Abstracts from the Genomics:GTL Contractor—Grantee Workshop IV, North Bethesda, MD, February 2006. Within http://doegenomestolife.org/pubs/2006abstracts/index.shtml
8. Research Topics Website, U.S. DOE OBER. (URL: http://www.sc.doe.gov/production/ober/restopic.html)
9. Hydrogen Production and Delivery: Photolytic Processes Website, U.S. DOE Office of Energy Efficiency and Renewable Energy. (URL: http://www.eere.energy.gov/hydrogenandfuelcells/production/photo_processes.html)
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