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Review of the Department of Energy’s Genomics: GTL Program Review of the Department of Energy’s Genomics: GTL Program Committee on Review of the Department of Energy’s Genomics: GTL Program Board on Life Sciences Division on Earth and Life Studies NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu
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Review of the Department of Energy’s Genomics: GTL Program THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This study was supported by Contract DE-AM01-04PI45013 between the National Academy of Sciences and the U.S. Department of Energy. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Energy, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. International Standard Book Number 0-309-10133-6 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, NW, Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. COVER: Geobacter, a microorganism that can be used for bioremediation of uranium-contaminated groundwater and shows substantial promise for harvesting electricity from otherwise low-value energy sources. Photo by Derek Lovley, University of Massachusetts, Amherst. Design by Michael Dudzik, the National Academies Press. Copyright 2006 by the National Academy of Sciences. All rights reserved. Printed in the United States of America.
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Review of the Department of Energy’s Genomics: GTL Program THE NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medicine The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org
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Review of the Department of Energy’s Genomics: GTL Program COMMITTEE ON REVIEW OF THE DEPARTMENT OF ENERGY’S GENOMICS: GTL PROGRAM JENNIE HUNTER-CEVERA (Chair), University of Maryland Biotechnology Institute, Rockville CHARLES R. CANTOR, Sequenom, Inc., San Diego, California WAH CHIU, Baylor College of Medicine, Houston, Texas DOUGLAS R. COOK, University of California, Davis ERIC W. KALER, University of Delaware, Newark THOMAS KALIL, University of California, Berkeley DAVID T. KINGSBURY, Gordon and Betty Moore Foundation, San Francisco, California CLAUDIA NEUHAUSER, University of Minnesota, St. Paul GREGORY A. PETSKO, Brandeis University, Waltham, Massachusetts MARIAM STICKLEN, Michigan State University, East Lansing LARRY P. WALKER, Cornell University, Ithaca, New York JANET WESTPHELING, University of Georgia, Athens Staff EVONNE P. Y. TANG, Study Director FRANCES E. SHARPLES, Director, Board on Life Sciences ANN H. REID, Program Officer JOSEPH C. LARSEN, Postdoctoral Research Associate SETH STRONGIN, Senior Program Assistant (through September 2005) ANNE F. JURKOWSKI, Program Assistant (since September 2005) NORMAN GROSSBLATT, Senior Editor
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Review of the Department of Energy’s Genomics: GTL Program BOARD ON LIFE SCIENCES COREY S. GOODMAN (Chair), Renovis, Inc., South San Francisco, California ANN M. ARVIN, Stanford University School of Medicine, Stanford, California JEFFREY L. BENNETZEN, University of Georgia, Athens RUTH BERKELMAN, Emory University, Atlanta, Georgia DEBORAH BLUM, University of Wisconsin, Madison R. ALTA CHARO, University of Wisconsin, Madison DENNIS CHOI, Merck Research Laboratories, West Point, Pennsylvania JEFFREY L. DANGL, University of North Carolina, Chapel Hill PAUL R. EHRLICH, Stanford University, Stanford, California JAMES M. GENTILE, Research Corporation, Tucson, Arizona JO HANDELSMAN, University of Wisconsin, Madison ED HARLOW, Harvard Medical School, Boston, Massachusetts DAVID HILLIS, University of Texas, Austin, Texas KENNETH H. KELLER, University of Minnesota, Minneapolis RANDALL MURCH, Virginia Polytechnic Institute and State University, Alexandria GREGORY A. PETSKO, Brandeis University, Waltham, Massachusetts STUART L. PIMM, Duke University, Durham, North Carolina JAMES TIEDJE, Michigan State University, East Lansing KEITH YAMAMOTO, University of California, San Francisco Staff FRANCES E. SHARPLES, Director KERRY A. BRENNER, Senior Program Officer ADAM P. FAGEN, Program Officer DENISE GROSSHANS, Financial Associate TOVA JACOBOVITS, Program Assiant ANNE F. JURKOWSKI, Program Assistant ANN H. REID, Program Officer MARILEE K. SHELTON-DAVENPORT, Senior Program Officer EVONNE P. Y. TANG, Senior Program Officer ROBERT T. YUAN, Senior Program Officer
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Review of the Department of Energy’s Genomics: GTL Program Preface The Department of Energy (DOE) is one of the most complex of the U.S. government science agencies. It has led the nation in advancing many fields of science from physics and biology to large-scale computation. It was DOE that started the Human Genome Project and the first subsurface microbiology program and provided unparalleled capacity to the scientific community to define macromolecular structures in its synchrotrons. DOE has other user facilities, such as the Joint Genome Institute, which enables many researchers to benefit from the data acquired through whole genome sequences of both macroorganisms and microorganisms. Today, DOE maintains 17 national laboratories across the United States equipped with the latest technologies and housing some of the brightest minds in the country. Some of the most pressing scientific and societal challenges that DOE has to deal with are finding alternative bioenergy sources, bioremediation of mixed wastes (radionuclide-contaminated organics), and enhancing carbon sequestration potentially to decrease the rate of global warming. All three of these fields of multidisciplinary research require understanding of complex biological systems starting at the organismal level and working down to the molecular level and vice versa. Recognizing that one cannot put the cart before the horse, especially if one is to design experiments at the bench to fit the reactor (applications in the field), DOE developed a forward-thinking program called Genomics: GTL (formerly Genomes to Life). The immediate goal of Genomics: GTL is to understand biological systems well enough to predict their behavior accurately with mechanistic computational models; the long-term goal of the program is to be able to develop microorganisms with capabilities for producing alternative energy sources, clean-
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Review of the Department of Energy’s Genomics: GTL Program ing up the Cold War legacy of contaminated waste sites, and elucidating carbon cycling and sequestration. The National Research Council (NRC) was asked to put together an ad hoc committee to review the design of the Genomics: GTL program and its infrastructure plan. We heard from various academic, industry, and national-laboratory scientists both funded and not funded by the program or involved with GTL, and we visited DOE headquarters in Germantown, Maryland, to meet and hear the perspective of the program’s managers. The committee met twice to discuss our findings and writing tasks and held numerous phone conferences over the 5-month period during which this report took shape. Our task was not an easy one by any standard, given the complexity of the science being evaluated and the need to unravel the Genomics: GTL components in order to understand better the planned future user facilities. The work of the committee was in some ways analogous to the Genomics: GTL program itself—examining the inner workings of a complex system so as to be able to design its functions for optimal output. I thank the committee members and the NRC staff for being so giving of their time and talent. It was an honor to serve as chair of such a distinguished group of scientists. We were on a very tight schedule to finish the report and had much to review and digest in a very short time. The committee’s discussions were stimulating and forward-thinking as to the role that DOE’s Genomics: GTL program could play in our country’s future in taking fundamental basic research all the way to translational research in the field, generating both important curiosity-driven discoveries and applied solutions for the most pressing challenges in bioremediation, bioenergy, and carbon sequestration. We came from many different backgrounds with diverse perspectives based on personal experiences, and yet we came together as a team focused on one mission, that of making a difference and moving DOE’s Genomics: GTL program to new heights based on the strong foundation it has established to date. Although the Genomics: GTL program had a “roadmap,” the committee paved its own road, bumps included, to reach a final consensus that the Genomics: GTL program is critical to the success of DOE’s mission and future as a leader in systems biology. Starting from this premise, the committee came up with a set of recommendations aimed at ensuring that this program would establish DOE as a world leader in microbial systems biology. The opportunity that Genomics: GTL offers scientists to advance both fundamental and applied knowledge in not only the mission focus areas of DOE but many other scientific endeavors worldwide is tremendous. Jennie Hunter-Cevera Chair, Committee on Review of the Department of Energy’s Genomics: GTL Program
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Review of the Department of Energy’s Genomics: GTL Program Acknowledgments This report is a product of the cooperation and contributions of many people. The committee would like to thank all the speakers who attended the first meeting of the committee, on September 25-26, 2005, and others who provided information and input. This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards of objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following for their review of this report: Nitin Baliga, Institute for Systems Biology, Seattle, Washington Peter Bottomley, Oregon State University, Corvallis Steven P. Briggs, University of California, San Diego Jeffrey L. Dangl, University of North Carolina, Chapel Hill Edward Dougherty, Texas A&M University, College Station Jed Fuhrman, University of Southern California, Los Angeles David Galas, Battelle, Columbus, Ohio Robert Haselkorn, University of Chicago, Chicago, Illinois Kenneth Keegstra, Michigan State University, East Lansing
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Review of the Department of Energy’s Genomics: GTL Program Karl Sanford, Genencor International, Palo Alto, California John Wooley, University of California, San Diego Although the reviewers listed above have provided constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by Dr. Christopher R. Somerville. Appointed by the National Research Council, Dr. Somerville was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the author committee and the institution.
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Review of the Department of Energy’s Genomics: GTL Program Contents SUMMARY 1 1 ROLE OF GENOMICS IN ADVANCING SCIENCE 9 Introduction, 9 Scientific Advances Brought by Genomics, 10 The Department of Energy as a Pioneer in Genomics Research, 12 Genomics: GTL Program, 17 2 ROLE OF GENOMICS: GTL IN ACHIEVING DOE’S MISSION GOALS: PROMISE AND CHALLENGES 25 Bioenergy, 26 Carbon Sequestration, 30 Bioremediation, 33 Challenges to the Achievement of the Department of Energy’s Mission Goals Through Systems Biology, 39 3 IMPLEMENTATION OF THE GENOMICS: GTL PROGRAM PLANS 47 The Proposed Genomics: GTL User Facilities, 48 An Alternative Model for Implementation, 52 Summary, 64
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Review of the Department of Energy’s Genomics: GTL Program GLOSSARY 67 REFERENCES 69 APPENDIXES A Committee Biographies 77 B Presentations to the Committee 83 C Research Institutes That Have Received Funds Through Contracts and Subcontracts from the Genomics: GTL Program 85 D Examples of Research in Microbial Genomics Supported by Federal Agencies Other Than DOE 87