Review of the Department of Energy’s

Genomics: GTL Program

Committee MembersJennie Hunter-Cevera, Chair, University of Maryland, Biotechnology

InstituteCharles R. Cantor, Sequenom, Inc.Wah Chiu, Baylor College of MedicineDouglas R. Cook, University of California, DavisEric W. Kaler, University of DelawareThomas Kalil, University of California, BerkeleyDavid T. Kingsbury, Gordon and Betty Moore FoundationClaudia Neuhauser, University of MinnesotaGregory A. Petsko, Brandeis UniversityMariam Sticklen, Michigan State UniversityLarry P. Walker, Cornell UniversityJanet Westpheling, University of Georgia

Committee Charge: To address the following three questions:

1. Is the Genomics: GTL program, as currently designed, scientifically and technically well-tailored to the challenges faced by the DOE in energy technology and development and environmental remediation?

Committee Charge (cont’d)2. Does the proposed Genomics: GTL research

and facility investment strategy leverage DOE scientific and technical expertise in the most cost-effective, efficient, and scientifically optimal manner?

Specifically, does the “business model” (i.e., number, scope, scale, order, and user operation plan) for the proposed Genomics: GTL facilities follow directly from the science case—should one exist—for systems biology at DOE?

Are there alternate models for some of the proposed effort that could more efficiently deliver the same scientific output?

Committee Charge (cont’d)

3. In an era of flat or declining budgets, which aspects of the proposed Genomics: GTL program are the most meritorious? Which appear to have the highest ratio of scientific benefit to cost?

GTL

• -- “aims to understand biological systems well enough to predict their behavior accurately with mechanistic computational models” so that such knowledge can be used to engineer systems for bioenergy production and environmental remediation and to understand carbon sequestration.

Study and Evaluation Process

• Two committee meetings were held, including one public meeting.

• Numerous teleconferences were held to gather information, draft the report and make final deliberations

• The committee heard from– Representatives of DOE– Academic, industry and national laboratories

scientists, both funded and not funded by DOE– Representatives of NSF, NIH, USDA, OMB, and

OSTP

Study and Evaluation Process (cont’d)

• The report was reviewed by 11 external reviewers.

• Report review process was overseen by report review coordinator.

• Final product is a consensus report of the committee.

Report Structure

• Role of Genomics in Advancing Science

• Role of Genomics: GTL in Achieving DOE’s Mission Goals: Promises and Challenges

• Implementation of the Genomics: GTL Program Plans

Question 1: Is the Genomics: GTL program, as currently designed, scientifically and technically well tailored to the challenges faced by the DOE in energy technology development and environmental remediation?

Answer 1: Yes, the use of systems and synthetic biology approaches in the Genomics: GTL program to address some of the most pressing issues in microbial genomics relevant to DOE’s mission in energy security, environmental remediation, and carbon cycling and sequestration is not only appropriate but necessary.

Answers to the Charge

Answer 1 (cont’d): The study of individual components only does not provide knowledge on systems integration at the level of pathways, organisms, and microbial consortia --for example, on the effects of introducing new metabolites or new or engineered organisms to a community; or on organism or community responses.

Systems biology research is needed to develop models for predicting the behavior of complex biological systems, to engineer microorganisms for bioremediation and energy-related needs, and to understand carbon cycling.

Question 2: Does the proposed Genomics: GTL research and facility investment strategy leverage DOE scientific and technical expertise in the most cost-effective, efficient, and scientifically optimal manner? Specifically, does the "business model” (i.e. number, scope, scale, order, and user operations plan) for the proposed Genomics: GTL facilities follow directly from the science case—should one exist—for systems biology at DOE? Are there alternate models for some or all of the proposed effort that could more efficiently deliver the same scientific output?

Answer 2: The committee enthusiastically endorses the goals of the Genomics: GTL program and acknowledges the need for infrastructure, but it believes that DOE’s current plan for building four independent facilities for protein production, molecular imaging, proteome analysis, and systems biology sequentially may not be the most cost-effective, efficient, and scientifically optimal way to provide this infrastructure.

As an alternative, the committee suggests the construction of up to four institute-like facilities, each of which integrates the capabilities of all four of the originally planned facility types and focuses on one or two of DOE’s mission goals.

Question 3: In an era of flat or declining budgets, which aspects of the proposed Genomics: GTL program are the most meritorious? Which appear to have the highest ratio of scientific benefit to cost?

Answer 3: The Genomics: GTL program’s research has resulted in and promises to deliver many more scientific advancements that contribute to the achievement of DOE mission goals. The committee proposes the initiation of facilities that integrate the four capabilities of protein production, molecular imaging, proteome analysis, and modeling and analysis of cellular systems because they are all necessary for achieving a predictive understanding of microbial systems through systems biology.

Answer 3 (cont’d): Therefore, the question of which facility with a distinct capability is the most meritorious is irrelevant. If DOE were to set up vertically integrated facilities, it would have to select which of its mission foci should be the targets of the first integrated facility. The committee suggests that bioenergy be its first choice given the pressing concern of energy security.

Recommendation 1

The committee recommends that DOE and the nation give high priority to genomics research aimed at achieving DOE’s mission goals.

DOE should revise its plans for creating four single purpose and technique-driven facilities in sequence. Instead, DOE should create up to four institute-like facilities that each contains all of 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 could focus on one or two of the DOE mission objectives and develop short, medium and long-term goals to chart a course for the program. Short-term milestones should be used as a metric for independent evaluation.

Recommendation 2

Merits of Vertically Integrated Facilities for Genomics: GTL Program

• 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.

• Research programs of the facilities would be built on overarching biological themes relevant to the DOE missions

• New technologies would be developed in the facilities on the basis of well-justified scientific problems.

Merits of Vertically Integrated Facilities for Genomics: GTL Program

• Attract investigators around the country to use them –leverage DOE’s ability to manage complex integrated research programs.

• New computational approaches and tools would be developed in the facility to promote synergy between modeling and experimentation at both bench and field level.

• First facility serves as a pilot to validate the hybrid approach and identify roadblocks – not be outdated.

• Have staged investments with expandable bases, flexibility to shift directions without losing prior investments, leverage and open-source positioning.

Recommendation 3DOE should consider locating user facilities on private land off DOE reservations to allow an open-access policy and in close proximity to research institutions that have established programs or centers of excellence in biosciences and biotechnology.

The locations for the user facilities should be selected via an open and all-inclusive competitive process that provides ample opportunity for universities and industry to partner with DOE and its national laboratories.

Recommendation 4

DOE should consider partnering with universities and other federal agencies to develop programs that employ Genomics: GTL institute-like facilities as training grounds for the next generation scientists.

Epilogue

DOE has done an exceptional job in leading the country in many areas of research that were at the cutting edge, in particular the Human Genome Project.

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 within DOE and other national and international agency programs.

Epilogue (cont’d)

The committee commends DOE for its forward development of the Genomics: GTL program and encourages the DOE administration to consider the committee’s proposed alternative plan for the Genomics: GTL facilities.

The recommendations in this report, if implemented, will enhance DOE’s potential for success in their three critical mission areas: bioenergy, bioremediation and carbon sequestration.

AND……..

March 28, 2006DOE OFFICE OF SCIENCE TO REVISE

PLANSFOR GENOMICS:GTL FACILITIESPlans to Issue New Solicitation

for GTL Bioenergy Research Centers

• The Department of Energy’s Office of Science announced today that it is revising its plans for the deployment of new research facilities to support its Genomics:GTL program.

• The decision to reshape plans for the new GTL research facilities comes in response to the President’s recently announced Advanced Energy Initiative and a review of the GTL program by the National Research Council (NRC) of the National Academies.

• Begun in 2000, the Office of Science’s GTL program supports advanced research in systems biology aimed at harnessing the powers of the microbial world to produce abundant and clean energy, absorb carbon dioxide, and transform radioactively contaminated waste.

• The specific goal of the new facilities plan will be to accelerate GTL systems biology research in the area of bioenergy, with the objective of developing cost-effective, biologically based renewable energy sources to reduce U.S. dependence on fossil fuels.

• The Office also said the new facilities plan, to be based partly on recommendations from the NRC panel, should be able to accomplish the GTL program’s objectives more rapidly and at reduced cost.

• As part of the reassessment, the Office of Science has cancelled its Funding Opportunity Announcement (FOA) for a planned GTL Facility for the Production and Characterization of Proteins and Molecular Tags, issued in early January.

• The Office of Science plans to issue a new solicitation in the coming months for one or more centers for bioenergy research.

• Centers focused on systems biology research into carbon sequestration and bioremediation are also being considered for future years.

• The NRC committee recommended that the GTL facilities should be focused not on particular technologies, but on research underpinning particular applications – bioenergy, carbon sequestration, or environmental remediation.

• Drawing on the NRC recommendations, the Office of Science is formulating a plan for one or two vertically integrated centers with a focus on bioenergy research.

• The Office believes that these centers can be operational at a date earlier than the originally planned Facility for the Production and Characterization of Proteins and Molecular Tags. The Office of Science plans to issue the new solicitation soon.