Review of the Department of Energy's Genomics: GTL Program (2006) / Chapter Skim
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2 Role of Genomics: GTL in Achieving DOE\'s Mission Goals: Promise and Challenges
2 Role of Genomics: GTL in Achieving DOE\'s Mission Goals: Promise and Challenges
Pages 25-46
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From page 25... ...
· To develop biological solutions for remediation of soil, sediment, and groundwater contaminated with metals, radionuclides, and organic hazardous wastes. · To understand relationships between climate change and Earth's microbial systems and to generate options for carbon sequestration.
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· Have the potential to compete effectively with fossil fuels in the marketplace. · Reduce the adverse environmental effects of today's pattern of energy production and consumption.
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Understanding of systems biology will lead to better methods and tools for manipulating and controlling metabolic pathways that are important for bioenergy and industrial chemical production, for prospecting for novel industrial enzymes and microorganisms, and for bioengineering to enhance plants' usability as feedstocks for energy and industrial chemicals. For example, one goal of the Genomics: GTL program is to discover functions of genes that could contribute to cheaper biofuels.
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Cost-effective and efficient microbial conversion processes are necessary to convert low-cost sugars derived from plant-based resources to ethanol and other industrial chemicals. Although there are several key technological differences in how ethanol is produced from corn or cellulosic feedstock, both paths to ethanol production require a fermentation step that involves the conversion of glucose and other sugars to ethanol.
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The science, methods, and tools of the Genomics: GTL program would strengthen our understanding of the regulatory and metabolic pathways that influence hydrogen production and create opportunities for more-informed engineering of those pathways and others. Although the focus of Genomics: GTL bioenergy research is on microbial processes, it should be clear from the preceding paragraphs that biomass for bioenergy is derived from plants.
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The growing scientific evidence that CO2 and other greenhouse gases are altering our climate has stimulated interest in CO2 sequestration as a means to counteract global climate change. The DOE mission with respect to carbon cycling and sequestration is to "understand the microbial mechanisms of carbon cycling in the earth's ocean and terrestrial ecosystems, the roles they play in carbon sequestration, and how these processes respond to and impact climate change." Photosynthetic terrestrial and aquatic organisms naturally perform biosequestration, and understanding how this is achieved at the whole-organism and microbial-community levels is one of the important roles of the Genomics: GTL program.
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Moreover, the resulting knowledge could enable predictive models of system function that might presage changes in the global carbon economy. Although currently missing from the Genomics: GTL research plan, plants contribute substantially to nutrient cycles in the soil through both photosynthesis and nitrogen fixation.
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Research is designed to establish the scientific basis for enhancing carbon capture and long-term sequestration in terrestrial ecosystems by developing: · "Scientific understanding of carbon capture and sequestration mechanisms in terrestrial ecosystems across multiple scales from the molecular to the landscape, · "Conceptual and simulation models for extrapolation of process understanding across spatial and temporal scales, · "Estimates of carbon sequestration potential, · "Assessments of environmental impacts and economic implications of carbon sequestration." The fourth question, on needed new technologies and computational systems, highlights the need to develop infrastructure for advancing the Genomics: GTL program. For example, metagenomic methods can document the makeup and activity of ocean communities involved in CO2 recycling.
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Obviously, answers to those questions require a broad interdisciplinary approach and will benefit from genomic studies to identify key genes and pathways. Understanding the complexity of ecosystems in which many functions are being carried out simultaneously by millions of microorganisms of diverse species is no small task; it will take years of study, including the development of novel experimental and computational approaches.
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The optimization of metabolic activities of whole organisms and microbial communities is the key to converting hazardous materials to nonhazardous materials or nonbioavailable forms and is consistent with the research and development activities of the Genomics: GTL program. The Genomics: GTL roadmap listed several research needs: · Assessment of benefits and effects.
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The work of Derek Lovley, of the University of Massachusetts, Amherst, on optimizing in situ bioremediation of uranium and harvesting electrical energy from waste organic matter by Geobacter species is an example of how genome sequences can be used as a launching point of understanding. His project addresses not only the identification and validation of the microbial community involved in the bioremediation of uranium in contaminated subsurface environments but also the use of this microbial community to harvest electricity from waste organic matter and renewable biomass.
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. FIGURE 2-1 A new species of radiation-resistant Deinococcus isolated from radioactive sediment be neath a leaking Hanford waste tank (DOE, 2002)
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The bacterium Caulobacter crescentus is known for its broad habitat, its dis tinctive ability to live in low-nutrient environments, and its being a model organism for studying cell-cycle regulation. Gary Andersen's group at the Lawrence Berke ley National Laboratory, in collaboration with Harley McAdams's group at Stanford University, identified the pathways responding to heavy-metal toxicity in C
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· Describe the metabolic capabilities of complex microbial communities in their natural environments. · Develop new computational methods and tools to increase the understanding of complex biological systems and predict their behavior.
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In its current form, Genomics: GTL has two parallel tracks: use of a traditional research funding process to identify and fund relatively large-scale, often multi-investigator projects focused on specific biological problems and a multidecade plan to construct and operate facilities that target high-throughput production and analysis of proteins, protein complexes, and microbial systems within which the proteins express their potential. The current facilities model assumes that progress in microbial systems biology is limited by lack of knowledge about proteins and their derived attributes within biological systems of interest to DOE, that acquiring such knowledge will require high-throughput facilities that can solve the problem by applying appropriate technology, and that knowledge of and access to all proteins in a range of target systems will revolutionize microbial systems biology in a way analogous to how genome sequencing has transformed biology in general.
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From page 40... ...
Recognition of that has sparked renewed interest in developing methods for enriching and culturing recalcitrant and rare species. Similar gains are likely to be realized by implementing nucleic acid normalization methods, such as Cot enrichment or suppressive-subtractive hybridization, which are well established in other genome investigations (for example, Yuan et al., 2003; Galbraith et al., 2004)
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From page 41... ...
The third problem is that sequence and structure information rarely, if ever, increases understanding of whether a gene product has important interactions with others in the cell and, if it does, how those interactions affect its biochemical and cellular roles. Relying too heavily on such data-gathering for functional annotation risks taking a step backward, away from the more complex pictures demanded by systems biology.
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From page 42... ...
But they are data at the lowest level of complexity, involve the most routine and readily available technologies, and should not be a cornerstone of a program designed to advance the cutting-edge field of systems biology. Computational Challenges The Genomics: GTL roadmap states that "the goal is to create increasingly accurate mathematical models of life processes that enable predictions of cell and community behavior and create new and modified systems tailored for mission applications." The systems biology approach of Genomics: GTL will integrate experiments, data acquisition and processing, modeling, and simulations in an iterative process in which model predictions inform experiments and experiments inform model development.
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that link cellular components, including gene networks, regulatory networks, and metabolic networks. Those networks provide a static view of cellular interactions.
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The following are insights: · Description and then development of predictive models for how complex microbial consortia respond to natural and imposed selection. · Identification of the genomic diversity best suited to manipulation of Genomics: GTL target processes, for example, remediation of specific contaminants in unique environments.
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· Development of new methods and instrumentation to measure key biological parameters that may be relevant to system function, including metabolite flow and protein function in vivo and in situ. · Establishment of methods to reproduce native ecologies in the laboratory or to analyze them in situ.
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From page 46... ...
Electrical circuits are composed of a rather small diversity of entities, whereas biological systems are composed of a multitude of dissimilar parts, even to the point of adaptive variation in apparently common components. Given the scale and complexity of the challenge, it is not obvious that a complete catalog and partial analysis of all proteins in a few target genomes would be a major advance toward understanding and predicting the function of complex microbial systems.
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