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A60 The Commercial Viability of EXCAVATOR : A Software Tool ForGene Expression Data Clustering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42Robin D. Zimmer, Morey Parang, Dong Xu, and Ying XuA62 Modeling Electron Transfer in Flavocytochrome c3 Fumarate Reductase. . . . . . . . 43Dayle M. Smith, Michel Dupuis, Erich R. Vorpagel, and T. P. StraatsmaEnvironmental GenomicsB1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45Identification and Isolation of Active, Non-Cultured Bacteria fromRadionuclide and Metal Contaminated Environments for Genome Analysis . . . . . 45Cheryl R. Kuske, Susan M. Barns, and Leslie E. SommervilleB3A Metagenomic Library of Bacterial DNA Isolated from the Delaware River . . . . 46David L. Kirchman, Matthew T. Cottrell, and Lisa WaidnerB5Approaches for Obtaining Genome Sequence from ContaminatedSediments Beneath a Leaking High-Level Radioactive Waste Tank . . . . . . . . . . . . 47Fred Brockman, Margaret Romine, Kristin Kadner, Paul Richardson, Karsten Zengler, Martin Keller,and Cheryl KuskeB7Ecological and Evolutionary Analyses of a Spatially and GeochemicallyConfined Acid Mine Drainage Ecosystem Enabled by Community Genomics . . . . 48Gene W. Tyson, Philip Hugenholtz, and Jillian F. BanfieldMicrobial Genomics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51B11 Strategies to Harness the Metabolic Diversity of Rhodopseudomonas palustris . . . . . . 51Caroline S. Harwood, Jizhong Zhou, F. Robert Tabita, Frank Larimer, Liyou Wu, Yasuhiro Oda,Federico Rey, and Sudip SamantaB13 Gene Expression Profiles in Nitrosomonas europaea, an ObligateChemolithoautotroph . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51Dan Arp, Xueming Wei, Luis Sayavedra-Soto, Martin G. Klotz, Jizhong Zhou, and Tingfen YanB15 Genomics of Thermobifida fusca Plant Cell Wall Degradating Proteins. . . . . . . . . . 52David B. Wilson, Yuan-Man Hsu, and Diana IrwinB17 The Rhodopseudomonas palustris Microbial Cell Project. . . . . . . . . . . . . . . . . . . . . . 53F. Robert Tabita, Janet L. Gibson, Caroline S. Harwood, Frank Larimer, Thomas Beatty, James C. Liao,Jizhong (Joe) Zhou, and Richard SmithSession and poster board numbers are indicated in the gray boxes.Genomes to Life Iv

B19 Lateral Gene Transfer and the History of Bacterial Genomes. . . . . . . . . . . . . . . . . 53Scott R. Santos and Howard OchmanB21 Environmental Sensing, Metabolic Response, and Regulatory Networksin the Respiratory Versatile Bacterium Shewanella oneidensis MR-1 . . . . . . . . . . . . . 54James K. Fredrickson, Margie F. Romine, William Cannon, Yuri A. Gorby, Mary S. Weir-Lipton,H. Peter Lu, Richard D. Smith, Harold E. Trease, and Shimon WeissA64 Interdisciplinary Study of Shewanella oneidensis MR-1’s Metabolismand Metal Reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56Eugene KolkerB23 Integrated Analysis of Protein Complexes and Regulatory Networks Involvedin Anaerobic Energy Metabolism of Shewanella oneidensis MR-1 . . . . . . . . . . . . . . 56Jizhong Zhou, Dorothea K. Thompson, Matthew W. Fields, Adam Leaphart, Dawn Stanek,Timothy Palzkill, Frank Larimer, James M. Tiedje, Kenneth H. Nealson, Alex S. Beliaev, Richard Smith,Bernhard O. Palsson, Carol Giometti, Dong Xu, Ying Xu, Mary Lipton, James R. Cole,and Joel KlappenbachB25 Global Regulation in the Methanogenic Archaeon Methanococcus maripaludis. . . . 57John Leigh, Murray Hackett, Roger Bumgarner, Ram Samudrala, William Whitman, Jon Amster,and Dieter SöllB27 Identification of Regions of Lateral Gene Transfer Across the Thermotogales. . . . 58Karen E. Nelson, Emmanuel Mongodin, Ioana Hance, and Steven R. GillB29 The Dynamics of Cellular Stress Responses in Deinococcus radiodurans. . . . . . . . . . 59Michael J. Daly, Jizhong Zhou, James K. Fredrickson, Richard D. Smith, Mary S. Lipton,and Eugene KooninB9Uncovering the Regulatory Networks Associated with IonizingRadiation-Induced Gene Expression in D. radiodurans R1 . . . . . . . . . . . . . . . . . . 60John R. Battista, Ashlee M. Earl, Heather A. Howell, and Scott N. PetersonB31 Analysis of Proteins Encoded on the S. oneidensis MR-1 Chromosome,Their Metabolic Associations, and Paralogous Relationships . . . . . . . . . . . . . . . . . 60Margrethe H. Serres, Maria C. Murray, and Monica RileyB33 Finishing and Analysis of the Nostoc punctiforme Genome. . . . . . . . . . . . . . . . . . . 61S. Malfatti, L. Vergez, N. Doggett, J. Longmire, R. Atlas, J. Elhai, J. Meeks,and P. ChainSession and poster board numbers are indicated in the gray boxes.viGenomes to Life I

B35 In Search of Diversity: Understanding How Post-Genomic Diversity isIntroduced to the Proteome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61Barry Moore, Chad Nelson, Norma Wills, John Atkins, and Raymond GestelandB37 The Microbial Proteome Project: A Database of Microbial Protein Expressionin the Context of Genome Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62Carol S. Giometti, Gyorgy Babnigg, Sandra L. Tollaksen, Tripti Khare, Derek R. Lovley,James K. Fredrickson, Kenneth H. Nealson, Claudia I. Reich, Gary J. Olsen, Michael W. W. Adams,and John R. Yates IIIB39 Analysis of the Shewanella oneidensis Proteome in Cells Grown inContinuous Culture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63Carol S. Giometti, Mary S. Lipton, Gyorgy Babnigg, Sandra L. Tollaksen, Tripti Khare,James K. Fredrickson, Richard D. Smith, Yuri A. Gorby, and John R. Yates IIIB41 The Molecular Basis for Metabolic and Energetic Diversity. . . . . . . . . . . . . . . . . . 64Timothy Donohue, Jeremy Edwards, Mark Gomelsky, Jonathan Hosler, Samuel Kaplan,and William MargolinB43 Integrative Studies of Carbon Generation and Utilization in theCyanobacterium Synechocystis sp. PCC 6803 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64Wim Vermaas, Robert Roberson, Julian Whitelegge, Kym Faull, Ross Overbeek, and Svetlana GerdesTechnology Development. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67B45 Comparative Optical Mapping: A New Approach for MicrobialComparative Genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67Shiguo Zhou, Thomas S. Anantharaman, Erika Kvikstad, Andrew Kile, Mike Bechner, Wen Deng,Jun Wei, Valerie Burland, Frederick R. Blattner, Chris Mackenzie, Timothy Donohue, Samuel Kaplan,and David C. SchwartzB47 Optical Mapping of Multiple Microbial Genomes. . . . . . . . . . . . . . . . . . . . . . . . . 67Shiguo Zhou, Michael Bechner, Erika Kvikstad, Andrew Kile, Susan Reslewic, Aaron Anderson,Rod Runnheim, Jessica Severin, Dan Forrest, Chris Churas, Casey Lamers, Samuel Kaplan,Chris Mackenzie, Timothy J. Donohue, and David C. SchwartzB49 Identification of ATP Binding Proteins within Sequenced Bacterial GenomesUtilizing Phage Display Technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68Suneeta Mandava, Lee Makowski, and Diane J. RodiB51 Development of Vectors for Detecting Protein-Protein Interactions in Bacteria. . . 69Peter Agron and Gary AndersenSession and poster board numbers are indicated in the gray boxes.Genomes to Life Ivii

B53 Development and Use of Microarray-Based Integrated Genomic Technologiesfor Functional Analysis of Environmentally Important Microorganisms . . . . . . . . 70Jizhong Zhou, Liyou Wu, Xiudan Liu, Tingfen Yan, Yongqing Liu, Steve Brown, Matthew W. Fields,Dorothea K. Thompson, Dong Xu, Joel Klappenbach, James M. Tiedje, Caroline Harwood, Daniel Arp,and Michael DalyB55 Electron Tomography of Whole Bacterial Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . 71Ken DowningB57 Single Cell Proteomics—D. radiodurans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71Norman J. DovichiB59 Genomes to Proteomes to Life: Application of New Technologies forComprehensive, Quantitative and High Throughput Microbial Proteomics . . . . . . 72Richard D. Smith, James K. Fredrickson, Mary S. Lipton, David Camp, Gordon A. Anderson,Ljiljana Pasa-Tolic, Ronald J. Moore, Margie F. Romine, Yufeng Shen, Yuri A. Gorby, and Harold R. UdsethB61 New Developments in Statistically Based Methods for Peptide Identificationvia Tandem Mass Spectrometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73Kenneth D. Jarman, Kristin H. Jarman, Alejandro Heredia-Langner, and William R. CannonAppendix 1: Attendees List . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75Appendix 2: Poster Presenters. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89Appendix 3: GTL Web Sites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97Institution Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103Meeting Agenda . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Inside Back CoverTotal Number of Abstracts: 64Session and poster board numbers are indicated in the gray boxes.viiiGenomes to Life I

Session and poster board numbers are indicated in the gray boxes.Genomes to Life Iix

Welcome to Genomes to LifeContractor-Grantee Workshop IWelcome to the first of what we hope will be many Genomes to Life (GTL) contractor-grantee workshops.Although only in its second official year of funding, GTL already is attracting broad and enthusiastic interestand support from scientists at universities, national laboratories, and industry; colleagues at other federalagencies; Department of Energy leadership; and Congress.You are part of an exciting era in biology as we begin to systematically leverage the knowledge and capabilities brought to us by DNA sequencing projects into an understanding of the functioning and control ofentire biological systems. GTL certainly is not the first, nor will it be the last, to conduct “systems biology”research, but we believe the program offers a roadmap for these new explorations. GTL research is, of necessity, at the interface of the physical, computational, and biological sciences.GTL will require the development of technologies that will enable us to “see” biology happen at finer scalesof resolution. It also will require a substantial integration of our broad capabilities in mathematics and computation with our new knowledge of biology. Only with this integration can we achieve GTL’s fundamentalgoal: to understand biological systems so well that we can accurately predict their behavior with sophisticated computational models.To enable this goal, GTL aims to develop these new technological, analytical, biological, and computationalcapabilities into cost-effective, widely accessible, high-throughput capabilities analogous to today’s DNAsequencing factories.Microbes are GTL’s principal biological focus. In the complex “simplicity” of microbes, we find capabilitiesneeded by DOE—indeed by our entire nation—for clean energy, cleanup of environmental contamination,and sequestration of atmospheric carbon dioxide that contributes to global warming. In addition, the fundamental knowledge and technologies developed in GTL will be broadly usable in all areas of biologicalresearch.This first GTL program workshop is an opportunity for all of us to discuss, listen, and learn about the exciting science, identify research needs and opportunities, form research partnerships, and share the excitementof this program with the broader scientific community.We look forward to a stimulating and productive meeting and offer our sincere thanks to all the organizersand to you, the scientists, whose vision and efforts will help us all to realize the promise of this excitingresearch program.Ari PatrinosEd OliverAssociate Director forBiological and Environmental ResearchOffice of ScienceU.S. Department of EnergyAssociate Director forAdvanced Scientific Computing ResearchOffice of ScienceU.S. Department of EnergyGenomes to Life Ixi

DOE/SC-0069Genomes to Life:Realizing the Potential ofthe Genome RevolutionJanuary 2003he remarkable successes of theHuman Genome Project and spin-offsrevealing the details of numerousgenomes—from microbes to plants tomice—provide the richest resource in thehistory of biology. These achievements nowempower scientists to address the ultimategoal of modern biology: to obtain a fundamental, comprehensive, and systematicunderstanding of life. This goal is founded,as is life itself, on the genome, whose genesencode the proteins that carry out mostcellular activities via a labyrinth of pathways and networks that make the cell“come alive” (see figure below).TCatalyzing Systems BiologyThe Department of Energy’s (DOE) Genomes to Life (GTL) program is combininghigh-throughput advanced technologiesand computation with the informationfound in microbial genomes to establish afoundation for achieving an understandingof living systems (see “Microbes for DOEMissions,” p. 2). GTL is designed to helplaunch biology onto a new trajectory tocomprehensively understand cellularprocesses in a realistic context. This newlevel of exploration, known as systemsbiology, will empower scientists to pursuecompletely new approaches to discovery,transforming biology to a more quantitative and predictive science. GTL scientificgoals target the fundamental processes ofliving systems by studying them on threelevels:DOEGenomesToLife.orgMolecular machines carry out chemicalreactions, generate mechanical forces,transport metabolites and ions, andmake possible every action of a biological system. A cell does not generate itsentire repertoire of molecular machinesat once. Genomic regulatory elementsdictate the particular set producedaccording to the organism’s life strategyand in response to environmental cues,including other microbial populations inthe larger ecological community.Understanding lifeprocesses at themolecular level is a“national sciencepriority.”A comprehensive approach to understanding biological systems thus extendsfrom individual cells to many cellsfunctioning in communities. Such studiesmust encompass proteins, molecularmachines, pathways, networks, cells,and, ultimately, their regulatory elements,cellular systems, and environments. Thisnext generation of biology is viable onlywith vastly increased computational andinformational capabilities to master thefull complexities of biological systems.Transforming biology withlarge-scale technologiesand computing . 2—OSTP-OMB FY 2004budget guidance memo;see p. 6.Catalyzing systemsbiology . 1Emerging technologies andcomputing for systemsbiology . 3–4Integrated user facilitiesdemocratizing accessto systems biologyresources . 5A growing mandate formolecular studies . 6Genomes to Life: From DNA Sequence to Living SystemsUnderstanding life at themolecular level1. Proteins and multicomponent molecularmachines that form all of the cell’sstructures and perform most of thecell’s work.2. Gene regulatory networks and pathwaysthat control cellular processes.3. Microbial communities in which groupsof cells carry out complex processes innature.Genes are made up of DNA and contain the information used by othercellular components (e.g., RNA and ribosomes, not shown here) tocreate proteins. A working cell is tightly packed with tens of thousands of proteins and other molecules, often working together asmultimolecular “machines” to perform essential cellular activities(see also cell figure, p. 5).

Large-Scale Technologies and Computing:Transforming Biologyust as DNA sequencing capability was completely inadequate at the beginning of the Human Genome Project (HGP), the quantity andcomplexity of data that must be collected and analyzedfor systems biology research far exceed current capabilities and capacities. The HGP taught that aspects ofbiological research can be made high-throughput andcost-effective (see graph, p. 5). Collecting and usingsuch data and reagents will require a new organizational model that coordinates and integrates dozens ofhigh-throughput technologies and approaches, somenot yet refined or even developed. This is the centralprinciple of GTL and indeed of all systems biologyresearch.J2Analysis of living systems will require a new generation of experimentation and the computational methods and capabilities to assimilate, understand, andmodel the data on the scale and complexity of realliving systems. Computing must guide the researchquestions and interpretation at every step.The knowledge base resulting from the GTL programwill provide the entire research community with data,models, and simulations of gene expression, pathways, and network systems; molecular machines; andcell and community processes. These new capabilitiesand resources will inspire revolutionary solutions toDOE mission needs and transform the entire lifesciences landscape, from agriculture to human health.Microbes for DOE Missions: Energy Security, Cleanup, Climate ChangeWhy Study Microbes?The ability of this planet to sustain life is largelydependent on microbes. They are the foundation of thebiosphere, controlling earth’s biogeochemical cyclesand affecting the productivity of the soil, quality ofwater, and global climate. As one of the most excitingfrontiers in biology today, microbial research is revealing the hidden architecture of life and the dynamic,life-sustaining processes on earth. The diversity andrange of their environmental adaptations mean thatmicrobes long ago “solved” many problems for whichscientists are seeking solutions today (see examples atright). The incomprehensible number of microbes isan untapped but valuable resource that ultimately maybe used to generate new energy sources (e.g., hydrogen for a new energy economy), new cleanup andindustrial processes, and new ways of using biology toaddress DOE missions.The ChallengeMicrobes

Germantown, MD 20874-1290 Prepared by Human Genome Management Information System Oak Ridge National Laboratory Oak Ridge, TN 37830 . Anthony Martino, Andrey Gorin, Todd Lane, Steven Plimpton, Nagiza Samatova, Ying Xu, Hashim Al-Hashimi, Charlie Strauss, Byung-Hoon Park, George Ostrouchov, Al Geist, William Hart,