Review of the Department of Energy

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Review of the Department of Energys Genomics
GTL Program
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Committee Members

• Jennie Hunter-Cevera, Chair, University of
  Maryland, Biotechnology Institute
• Charles R. Cantor, Sequenom, Inc.
• Wah Chiu, Baylor College of Medicine
• Douglas R. Cook, University of California, Davis
• Eric W. Kaler, University of Delaware
• Thomas Kalil, University of California, Berkeley
• David T. Kingsbury, Gordon and Betty Moore
  Foundation
• Claudia Neuhauser, University of Minnesota
• Gregory A. Petsko, Brandeis University
• Mariam Sticklen, Michigan State University
• Larry P. Walker, Cornell University
• Janet Westpheling, University of Georgia

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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?

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Committee Charge (contd)

• 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 caseshould one
  existfor systems biology at DOE?
• Are there alternate models for some of the
  proposed effort that could more efficiently
  deliver the same scientific output?

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Committee Charge (contd)

• 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?

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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.

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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

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Study and Evaluation Process (contd)

• 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.

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Report Structure

• Role of Genomics in Advancing Science
• Role of Genomics GTL in Achieving DOEs Mission
  Goals Promises and Challenges
• Implementation of the Genomics GTL Program Plans

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Answers to the Charge
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 DOEs mission in energy security,
environmental remediation, and carbon cycling and
sequestration is not only appropriate but
necessary.
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Answer 1 (contd) 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.
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• 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 caseshould one existfor
  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?

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• Answer 2 The committee enthusiastically
  endorses the goals of the Genomics GTL program
  and acknowledges the need for infrastructure, but
  it believes that DOEs 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 DOEs mission goals.

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• 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 programs 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.

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• Answer 3 (contd) 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.

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Recommendation 1

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

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Recommendation 2

• 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 typesprotein production, molecular
  imaging, whole proteome analysis, and systems
  biologyin 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.

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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.

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Merits of Vertically Integrated Facilities for
Genomics GTL Program

• Attract investigators around the country to use
  them leverage DOEs 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.

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Recommendation 3

• DOE 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.

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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.
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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.
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Epilogue (contd)
The committee commends DOE for its forward
development of the Genomics GTL program and
encourages the DOE administration to consider the
committees proposed alternative plan for the
Genomics GTL facilities. The
recommendations in this report, if implemented,
will enhance DOEs potential for success in their
three critical mission areas bioenergy,
bioremediation and carbon sequestration.
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AND.. March 28, 2006 DOE OFFICE OF SCIENCE TO
REVISE PLANSFOR GENOMICSGTL FACILITIES Plans to
Issue New Solicitation for GTL Bioenergy
Research Centers
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• The Department of Energys Office of Science
  announced today that it is revising its plans for
  the deployment of new research facilities to
  support its GenomicsGTL program.
• The decision to reshape plans for the new GTL
  research facilities comes in response to the
  Presidents 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 Sciences 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.

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• 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
  programs objectives more rapidly and at reduced
  cost.

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• 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.

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• 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.

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• 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.

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Thank You for your time and attention.