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PROMISE AND CHALLENGES N SYSTEMS MICROBIOLOGY WORKSHOP SUMMARY Patricia McAJams Evonne Tang 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.eciu

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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 NOTICE: The project that is the subject of this summary 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 group responsible for the planning of the workshop were chosen for their special competences and with regard for appropriate balance. This material is based on work supported by the United States Department of Energy under Grant DE-FG-02-OOER62941. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the Department of Energy. International Standard Book Number 0-309-09167-5 (Book) International Standard Book Number 0-309-53077-6 (PDF) Additional copies of this summary 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. Copyright 2004 by the National Academy of Sciences. All rights reserved. Printed in the United States of America.

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THE NATIONAL ACADEMIES Advisers to the Nation on Stienre, Engineering, and Medicine The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distin- guished 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. Bruce M. Alberts 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 commu- nities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www. nationa l-academies.org

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PLANNING GROUP FOR THE WORKSHOP ON PROGRESS AND PROMISE IN SYSTEMS MICROBIOLOGY JOHN C. DOYLE (Cochair), California Institute of Technology, Pasadena ABIGAIL SAYLERS (Cochair), University of Illinois, Urbana-Champaign ALAN HASTINGS, University of California, Davis DEREK R. LOVELY, University of Massachusetts, Amherst MICHAEL SAVAGEAU, University of California, Davis LYLE WHYTE. McGill University, Quebec, Canada Staff EVONNE TANG, Study Director ROBIN SCHOEN, Senior Program Officer FRANCES SHARPLES, Director, Board on Life Sciences BRIDGET AVILA, Senior Project Assistant DANIELLE GREENE, Research Intern NORMAN GROSSBLATT, Senior Editor

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BOARD ON LIFE SCIENCES COREY S. GOODMAN, (Chair) University of California, Berkeley RUTH BERKELMAN, Emory University, Atlanta, Georgia R. ALTA CHARD, University of Wisconsin, Madison DENNIS CHOI, Merck Research Laboratories, West Point, Pennsylvania JOANNE CHORY, The Salk Institute for Biological Studies, La Jolla, California JEFFREY L. DANGL, University of North Carolina, Chapel Hill PAUL R. EHRLICH, Stanford University, Palo Alto, California {AMES M. GENTILE, Hope College, Holland, Michigan LINDA GREER, Natural Resources Defense Council, Washington, District of Columbia ED HARLOW, Harvard Medical School, Cambridge, Massachusetts DAVID HILLIS, University of Texas, Austin KENNETH F. KELLER, University of Minnesota, Minneapolis RANDALL MURCH, Institute for Defense Analyses, Alexandria, Virginia GREGORY A. PETSKO, Brandeis University, Waltham, Massachusetts STUART L. PIMM, Columbia University, New York, New York BARBARA A. SCHAAL, Washington University, St. Louis, Missouri {AMES TIEDIE, Michigan State University, East Lansing KEITH YAMAMOTO, University of California, San Francisco Senior Staff FRANCES SHARPLES v'

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Preface n 1993, the National Research Council's Board on Biology established a series of workshops on biotechnology. The purpose of the discussions is to foster open communication among scientists, administrators, policy- makers, and others engaged in biotechnology research, development, and commercialization. The neutral setting offered by the National Research Council is intended to promote mutual understanding among government, industry, and academe and to help develop imaginative approaches to prob- lem solving. However, the objective is to illuminate issues, not to resolve them. Unlike study committees of the National Research Council, work- shops cannot provide advice or recommendations to any government agency or other organization. Similarly, summaries of workshops do not reach conclusions or present recommendations but instead reflect the variety of opinions expressed by the participants. The comments in this report reflect the views of the workshop participants as indicated in the text. The first workshop, held in 1996, focused on intellectual property rights issues related to plant biotechnology. Other workshops have focused on broad issues related to developing an agricultural genome project, privacy in biomedical and clinical research, and the field of bioinformatics. On August 19, 2003, the Board on Life Sciences held the workshop on "Progress and Promise in Systems Microbiology." The systems approach attempts to use comparative, high-throughput assays and mathematical or computational models to generate a picture of system-wide activity that can yield insight into processes operating within the system. The workshop brought together scientists in academe, government, and other institutions . . v''

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. . . vail PREFACE with representatives of the US Department of Energy, the National Science Foundation, and the National Academies. The focus of the workshop was on communication among scientists in different disciplines pertinent to the application of systems biology to microbial ecology, with a goal of facilitat- ing transition among science and application and information dissemina- tion. The training of next-generation scientists with an emphasis on the interface of biology and computational biology was also stressed during the workshop. Several themes emerged during the discussions, which began with con- crete case studies of particular microbial systems and proceeded to research and educational needs to support further development of the field. Micro- bial ecosystems offer unique opportunities for practical bioengineering applications and attractive mode! systems for basic biological research. Sub- stantial basic research is needed to develop the theory, software tools, and experimental methods required to support systems microbiology, but the case studies showed that progress has already been made by coupling math- ematical modeling with experimentation. There was wide agreement that tight interactions of too! development with practical applications is needed, not only to keep too! development relevant and motivated but also because the current challenges for microbiologists in dealing with the enormous complexity of their systems and data can benefit from incremental progress in modeling, simulation, and analysis tools. John C. Doyle Cochair, Workshop on Progress and Promise in Systems Microbiology Evonne Tang Study Director

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Acknowledgments his document presents the rapporteur's summary of the workshop discussions and does not necessarily reflect the views of the round- table members or other participants. This summary has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC's Report Review Committee. The pur- pose of this independent review is to provide candid and critical comments that will assist the institution in making its published summary as sound as possible and to ensure that the summary meets institutional standards for 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 individuals for their review of this summary: Timothy Donohue, University of Wisconsin, Madison Phil Harriman, EPSCoR Centers Development Initiative Reinhard Laubenbacher, Virginia Polytechnic Institute and State University Gary S. Sayler, University of Tennessee, Knoxville The review of this summary was overseen by George Kenyon, University of Michigan. Appointed by the National Research Council, he was respon- sible 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 summary rests entirely with the institution. Nix

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Contents 1 INTRODUCTION 2 WORKSHOP PROCEEDINGS Microbial Systems: Case Studies, 3 Exploring Microbial Systems, 9 Modeling The Too! for Understanding Systems, 12 Tools for Systems-Microbiology Studies, 18 Looking Ahead Collaboration and Education, 23 Concluding Remarks, 26 3 SUMMARY OF KEY POINTS APPENDIXES A AGENDA B PARTICIPANT BIOGRAPHIES x' 1 3 27 29 31

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