Review of the Department of Energy's Genomics: GTL Program (2006) / Chapter Skim
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3 Implementation of the Genomics: GTL Progam Plans
3 Implementation of the Genomics: GTL Progam Plans
Pages 47-66
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From page 47... ...
The committee suggests the inclusion of plant biology research in the Genomics: GTL program where appropriate. In Genomics: GTL, DOE proposes to use systems and synthetic biology approaches to achieve a predictive understanding of microorganisms and to mine these untapped resources.
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From page 48... ...
The committee enthusiastically endorses DOE's plan to enlarge the program to $200 million per year for basic research and further endorses the focus of this research on long-term goals for energy production, environmental remediation, and the mitigation of global climate change. In particular, the committee notes that the ability to produce costcompetitive ethanol from cellulose and hydrogen biophotolytically from water or fermentatively from other carbon substrates, the development of biological solutions to the many recalcitrant problems of legacy wastes, and the attainment of an increased understanding of the role of microbial communities in global carbon cycling to enable the development of carbon-sequestration techniques for addressing climate change are all worthy goals that are highly suitable to DOE's missions.
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From page 49... ...
Second, the proposed configuration for the Genomics: GTL facilities is based on an underlying assumption that large-scale generation of reagents and data is the best way to apply a systems biology approach to the grand challenges of the Genomics: GTL program -- bioremediation, bioenergy, and carbon sequestration. That approach first parses the organisms that might be subjects for study into their components, assembles a parts list, inventories the parts, and then reassembles them into interacting complexes, networks, and pathways.
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From page 50... ...
The committee finds, however, that the analogy is weak at best. The economies of scale that made large genome projects successful have not yet been obtained in work with proteins or in most aspects of systems and synthetic biology.
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From page 51... ...
Given the magnitude of cur rent Genomics: GTL activities, it appears that program needs could be satisfied in a cost-effective way by using available technology and getting open bids from currently active players. Thus, if funds could be made available at the magnitude originally specified in the Genomics: GTL program, there ought to be sufficient resources to fund a number of smaller vertically integrated efforts that could not only produce the proteins but also amply apply them toward the research goals of the program.
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From page 52... ...
It is the view of the committee, however, that the real barriers are related to our ability to study and understand complexity and that a more problem-oriented approach is needed. Our list of key barriers includes barriers to measuring metabolite flow and other biological characters in vivo; to an understanding of interactions in communities of microorganisms that would enable prediction of the effects of introducing new metabolites or new or engineered organisms into the community; to a predictive understanding of how organisms respond to the introduction of new enzymes and pathways; to our ability to model microbial behavior in many developmental states, including stationary phase and sporulation, and in proliferation; to an understanding of transient states; to the acquisition of tools, including mathematical models and concepts, to enable prediction; to the use of general principles; and to adequate characterization of microbial diversity in the target ecosystems.
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From page 53... ...
In addition, a DOE initiative that is isolated from the broader biological community may not be taking full advantage of outside expertise or of opportunities to communicate its own expertise to others. The committee suggests that the optimal placement for Genomics: GTL facilities would be close to strong academic or industrial research establishments.
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From page 54... ...
And it integrates the Genomics: GTL program into the larger biological research community. In facing the reality of rapid scientific progress and the timeliness of the proposed approaches, the committee strongly encourages DOE to rethink its user facility construction plans and create institute-like facilities each of which combines the capabilities of the original four planned types in a vertically integrated manner.
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From page 55... ...
. The first vertically integrated facility could reduce its focus from all six conceptual science roadmaps and concentrate on only one or two.
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From page 56... ...
Instead, DOE should create up to four institute-like facilities that each contain all the capabilities of the original planned facility types -- protein production, molecular imaging, whole-proteome analysis, and systems biology -- in a vertically integrated manner. Each facility should focus on one or two of the DOE mission objectives and develop short-term, medium-term and long-term goals to chart a course for the program.
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From page 57... ...
· Vertically integrated facilities would establish the Genomics: GTL program in a leadership position to launch a world-class, comprehensive, integrated research and training program in systems and synthetic biology. They would create a paradigm shift in biological research that will integrate data from a broad spectrum of spatial and temporal scales to advance understanding of biological phenomena to be able to predict or alter capabilities for optimal performance under field conditions.
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From page 58... ...
The committee strongly believes that such an open and inclusive competition will provide DOE with a robust and enabling facility that could strongly support systems biology research. The criteria for the selection of contractors should include innovations of the project plan relevant to DOE missions, investigator qualifications, management organization, educational outreach, technology dissemination, strategy for maintaining the interface between Genomics: GTL research and industry and other entities that conduct translational research, intellectual-property management plan, proximity to a concentration of high-caliber participating scientists, and possibly provision of matching funds by the applicant institutions.
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From page 59... ...
The locations for the user facilities should be selected in an open and all-inclusive competitive process that provides adequate opportunities for universities and industry to partner with DOE and its national laboratories. The committee recognizes that the proposed integrated Genomics: GTL facilities would have a logical linkage to various large-scale enterprises, such as the nanoscience and high-performance computing programs supported by DOE, NSF, the National Institutes of Health (NIH)
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From page 60... ...
That argues strongly for the importance of simultaneously studying molecular components in the cellular context. All the projects in the proposed integrated facilities would involve multiple investigators, so a user-friendly data-management system across domains of in
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From page 61... ...
Overlap with Other Federal Agencies Because there is no such vertically integrated facility dedicated to studying biofuel, bioremediation, and carbon management, there is no direct competition with other agencies or anyone else. On the contrary, it is conceivable that a successful applicant will be able to partner with other investigators to leverage some of the existing but smaller-scale operations of various modules of technologies in protein and machine purification, mass spectroscopy, crystallography, electron cryomicroscopy, light microscopy, laboratory information management, and computer simulation and modeling.
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From page 62... ...
Such activities have been well conducted in the DOE laboratories in various disciplines -- for example, contractor-grantee workshops of the Human Genome Project and Genomics: GTL program and Sandia National Laboratory's Workshop on Computational Molecular Biology. The proposed Genomics: GTL facilities could provide unique and unusually rich technology environments for junior scientists to be introduced into research, to get excited about research related to our environment and energy production, to learn specialized techniques, and to develop research careers in microbial biology.
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From page 63... ...
Both DOE and NSF have sponsored competitive and successful summer research programs -- for example, Science Undergraduate Laboratory Internships at DOE and Research Experiences for Undergraduates at NSF. The Genomics: GTL program should create a prestigious undergraduate summer research program that would introduce students to the importance and excitement of microbial systems biology as applied to energy or environmental problems.
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From page 64... ...
Programs similar to those will allow the Genomics: GTL program researchers to gain access to a broad pool of talented graduate students. A successful graduate training program is an effective way of disseminating the Genomics: GTL resources and technologies to the broader biological community.
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From page 65... ...
The alternative model would consist of several problem-oriented facilities that are vertically integrated and institute-like (Box 3-3)
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From page 66... ...
DOE now has an opportunity to become a world leader in systems biology through the Genomics: GTL program and by integrating or connecting fundamental research data to other programs in DOE and other national and international agency programs. The committee commends DOE for its development of the Genomics: GTL program and encourages the DOE administration to consider the committee's proposed alternative plan for the Genomics: GTL facilities.
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