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Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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THE SCIENCE AND APPLICATIONS
OF
SYNTHETIC AND SYSTEMS BIOLOGY

Workshop Summary

Eileen R. Choffnes, David A. Relman, and Leslie Pray, Rapporteurs


Forum on Microbial Threats

Board on Global Health

INSTITUTE OF MEDICINE
         OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
×

THE NATIONAL ACADEMIES PRESS     500 Fifth Street, N.W.     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.

Financial support for this project was provided by the U.S. Department of Health and Human Services: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Centers for Disease Control and Prevention, Food and Drug Administration, and the Fogarty International Center; U.S. Department of Defense, Department of the Army: Global Emerging Infections Surveillance and Response System, Medical Research and Materiel Command, and the Defense Threat Reduction Agency; U.S. Department of Veterans Affairs; U.S. Department of Homeland Security; U.S. Agency for International Development; American Society for Microbiology; sanofi pasteur; Burroughs Wellcome Fund; Pfizer, Inc.; GlaxoSmithKline; Infectious Diseases Society of America; and the Merck Company Foundation. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

International Standard Book Number-13: 978-0-309-21939-6
International Standard Book Number-10: 0-309-21939-6

Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.

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Copyright 2011 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

Cover images: (Upper): Adapted from Mayr, E. 2004. De la bacteria la om—Evolutia lumii vii. Bucharest, Romania:Humanitas; (Lower): GloFish® fluorescent fish. Genetically modified Danio rerio. Photo courtesy of www.glofish.com.

The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.

Suggested citation: IOM (Institute of Medicine). 2011. The Science and Applications of Synthetic and Systems Biology. Washington, DC: The National Academies Press.

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
×

Knowing is not enough; we must apply.
Willing is not enough; we must do.
”      

                                                —Goethe

image

INSTITUTE OF MEDICINE
                OF THE NATIONAL ACADEMIES

Advising the Nation. Improving Health.

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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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. Charles M. Vest 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. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.

www.national-academies.org

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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FORUM ON MICROBIAL THREATS1

DAVID A. RELMAN (Chair), Stanford University and Veterans Affairs Palo Alto Health Care System, Palo Alto, California

JAMES M. HUGHES (Vice-Chair), Global Infectious Diseases Program, Emory University, Atlanta, Georgia

LONNIE J. KING (Vice-Chair), Ohio State University, Columbus, Ohio

KEVIN ANDERSON, Biological and Chemical Defense Division, Science and Technology Directorate, Department of Homeland Security, Washington, DC

RUTH L. BERKELMAN, Center for Public Health Preparedness and Research, Rollins School of Public Health, Emory University, Atlanta, Georgia

DAVID BLAZES,2 Armed Forces Health Surveillance Center, Division of Global Emerging Infectious Surveillance, Silver Spring, Maryland

ENRIQUETA C. BOND, Burroughs Wellcome Fund (Emeritus), Marshall, Virginia

ROGER G. BREEZE, Lawrence Livermore National Laboratory, Livermore, California

PAULA R. BRYANT, Defense Threat Reduction Agency, Medical S&T Division, Fort Belvoir, Virginia

JOHN E. BURRIS, Burroughs Wellcome Fund, Research Triangle Park, North Carolina

ARTURO CASADEVALL,2 Albert Einstein College of Medicine, Bronx, New York

PETER DASZAK, EcoHealth Alliance, New York, New York

JEFFREY S. DUCHIN, Public Health–Seattle and King County, Seattle, Washington

JONATHAN EISEN, Genome Center, University of California, Davis, California

RALPH L. ERICKSON,2 Walter Reed Army Institute of Research, Silver Spring, Maryland

MARK B. FEINBERG, Merck Vaccine Division, Merck & Co., West Point, Pennsylvania

JACQUELINE FLETCHER, Oklahoma State University, Stillwater, Oklahoma

JESSE L. GOODMAN, Food and Drug Administration, Silver Spring, Maryland

EDUARDO GOTUZZO, Instituto de Medicina Tropical–Alexander von Humbolt, Universidad Peruana Cayetano Heredia, Lima, Peru

_______________

1 Institute of Medicine Forums and Roundtables do not issue, review, or approve individual documents. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.

2 Forum member since September 1, 2011.

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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CAROLE A. HEILMAN, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

DAVID L. HEYMANN, Health Protection Agency, London, United Kingdom

ZHI HONG,3 GlaxoSmithKline, Research Triangle Park, North Carolina

PHILIP HOSBACH, sanofi pasteur, Swiftwater, Pennsylvania

STEPHEN ALBERT JOHNSTON, Arizona BioDesign Institute, Arizona

State University, Tempe, Arizona

KENT KESTER,4 Walter Reed Army Institute of Research, Silver Spring, Maryland

GERALD T. KEUSCH, Boston University School of Medicine and Boston University School of Public Health, Boston, Massachusetts

RIMA F. KHABBAZ, Centers for Disease Control and Prevention, Atlanta, Georgia

STANLEY M. LEMON, School of Medicine, University of North Carolina, Chapel Hill

EDWARD McSWEEGAN, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

MARK A. MILLER, National Institutes of Health, Fogarty International Center, Bethesda, Maryland

PAUL F. MILLER,5 Pfizer, Inc., Groton, Connecticut

GEORGE POSTE, Complex Adaptive Systems Initiative, Arizona State University, Tempe, Arizona

JOHN C. POTTAGE, JR.,6 ViiV Healthcare, Collegeville, Pennsylvania

DAVID RIZZO,7 Department of Plant Pathology, University of California, Davis, California

GARY A. ROSELLE, Veterans Health Administration, Department of Veterans Affairs, Cincinnati, Ohio

ALAN S. RUDOLPH, Defense Threat Reduction Agency, Fort Belvoir, Virginia

KEVIN RUSSELL, Armed Forces Health Surveillance Center, Department of Defense, Silver Spring, Maryland

JANET SHOEMAKER, American Society for Microbiology, Washington, DC

P. FREDERICK SPARLING, University of North Carolina, Chapel Hill, North Carolina

TERENCE TAYLOR, International Council for the Life Sciences, Arlington, Virginia

_______________

3 Forum member since November 1, 2011.

4 Forum member until August 31, 2011.

5 Forum member until July 31, 2011.

6 Forum member until October 31, 2011.

7 Forum member since September 1, 2011.

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
×

MURRAY TROSTLE, U.S. Agency for International Development, Washington, DC

MARY E. WILSON, Harvard School of Public Health, Harvard University, Boston, Massachusetts

Staff

EILEEN CHOFFNES, Director

LEIGHANNE OLSEN, Program Officer

KATHERINE McCLURE, Senior Program Associate

COLLIN WEINBERGER, Research Associate (until May 2011)

REBEKAH HUTTON, Research Associate (from June 2011)

ROBERT GASIOR, Senior Program Assistant (until March 2011)

PAMELA BERTELSON, Senior Program Assistant (from September 2011)

Page viii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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BOARD ON GLOBAL HEALTH1

Richard Guerrant (Chair), Thomas H. Hunter Professor of International Medicine and Director, Center for Global Health, University of Virginia School of Medicine, Charlottesville, Virginia

Jo Ivey Boufford (IOM Foreign Secretary), President, New York Academy of Medicine, New York

Claire V. Broome, Adjunct Professor, Division of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia

Jacquelyn C. Campbell, Anna D. Wolf Chair, and Professor, Johns Hopkins University School of Nursing, Baltimore, Maryland

Thomas J. Coates, Professor, David Geffen School of Medicine, University of California, Los Angeles, California

Gary Darmstadt, Director, Family Health Division, Global Health Program, Bill & Melinda Gates Foundation, Seattle, Washington

Valentin Fuster, Director, Wiener Cardiovascular Institute Kravis Cardiovascular Health Center, and Professor, Cardiology, Mount Sinai School of Medicine, Mount Sinai Medical Center, New York, New York

James Hospedales, Coordinator, Chronic Disease Project, Health Surveillance and Disease Management Area, Pan American Health Organization and World Health Organization, Washington, DC

Peter J. Hotez, Professor and Chair, Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC

Clarion Johnson, Global Medical Director, Medicine and Occupational Medicine Department, Exxon Mobil, Fairfax, Virginia

Fitzhugh Mullan, Professor, Department of Health Policy, George Washington University, Washington, DC

Guy Palmer, Regents Professor of Pathology and Infectious Diseases, Director of the School for Global Animal Health, Washington State University, Pullman, Washington

Jennifer Prah-Ruger, Associate Professor, Division of Health Policy and Administration, Yale University School of Public Health, New Haven, Connecticut

Staff

Patrick Kelley, Director

Angela Christian, Program Associate

_______________

1 Institute of Medicine boards do not review or approve individual workshop summaries. The responsibility for the content of the workshop summary rests with the workshop rapporteurs and the institution.

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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Reviewers

This report has been reviewed in draft form by individuals 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 scientifically sound as possible and to ensure that the report 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 process. We wish to thank the following individuals for their review of this report:

Noubar Afeyan, Massachusetts Institute of Technology
Frances Arnold, California Institute of Technology
Enriqueta C. Bond, Burroughs Wellcome Fund
Alan Rudolph, Defense Threat Reduction Agency

Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the final draft of the report before its release. The review of this report was overseen by Dr. Melvin Worth. Appointed by the Institute of Medicine, Dr. Worth was responsible for ensuring 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 authoring committee and the institution.

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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Acknowledgments

The Forum on Emerging Infections was created by the Institute of Medicine (IOM) in 1996 in response to a request from the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH). The purpose of the Forum is to provide structured opportunities for leaders from government, academia, and industry to regularly meet and examine issues of shared concern regarding research, prevention, detection, and management of emerging, reemerging, and novel infectious diseases in humans, plants, and animals. In pursuing this task, the Forum provides a venue to foster the exchange of information and ideas, identify areas in need of greater attention, clarify policy issues by enhancing knowledge and identifying points of agreement, and inform decision makers about science and policy issues. The Forum seeks to illuminate issues rather than resolve them. For this reason, it does not provide advice or recommendations on any specific policy initiative pending before any agency or organization. Its value derives instead from the diversity of its membership and from the contributions that individual members make throughout the activities of the Forum. In September 2003, the Forum changed its name to the Forum on Microbial Threats.

The Forum on Microbial Threats and the IOM wish to express their warmest appreciation to the individuals and organizations who gave their valuable time to provide information and advice to the Forum through their participation in the planning and execution of this workshop. A full list of presenters, and their biographical information, may be found in Appendixes B and F, respectively.

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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The Forum gratefully acknowledges the contributions of the members of the planning committee1: James J. Collins (Boston University), Stephen A. Johnston (Arizona State University), George Poste (Arizona State University), and P. Frederick Sparling (University of North Carolina).

The Forum is indebted to the IOM staff who tirelessly contributed throughout the planning and execution of the workshop and the production of this workshop summary report. On behalf of the Forum, we gratefully acknowledge these efforts led by Dr. Eileen Choffnes, director of the Forum; Dr. LeighAnne Olsen, program officer; Katherine McClure, senior program associate; Rebekah Hutton, research associate; Collin Weinberger, research associate; and Robert Gasior and Pamela Bertelson, senior program assistants, for dedicating much effort and time to developing this workshop’s agenda and for their thoughtful and insightful approach and skill in planning for the workshop and in translating the workshop’s proceedings and discussion into this workshop summary report. We would also like to thank the following IOM staff and consultants for their valuable contributions to this activity: Jill Grady, Laura Harbold, Leslie Pray, Heather Phillips, and Vilija Teel.

Finally, the Forum wishes to recognize the sponsors that supported this activity. Financial support for this project was provided by the U.S. Department of Health and Human Services: NIH, National Institute of Allergy and Infectious Diseases, CDC, Food and Drug Administration, and the Fogarty International Center; U.S. Department of Defense, Department of the Army: Global Emerging Infections Surveillance and Response System, Medical Research and Materiel Command, and the Defense Threat Reduction Agency; U.S. Department of Veterans Affairs; U.S. Department of Homeland Security; U.S. Agency for International Development; American Society for Microbiology; sanofi pasteur; Burroughs Wellcome Fund; Pfizer, Inc.; GlaxoSmithKline; Infectious Diseases Society of America; and the Merck Company Foundation. The views presented in this workshop summary report are those of the workshop participants and rapporteurs and are not necessarily those of the Forum on Microbial Threats or its sponsors.

_______________

1 Institute of Medicine planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.

Page xiii Cite
Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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A8   Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome

Daniel G. Gibson, John I. Glass, Carole Lartigue, Vladimir N. Noskov, Ray-Yuan Chuang, Mikkel A. Algire, Gwynedd A. Benders, Michael G. Montague, Li Ma, Monzia M. Moodie, Chuck Merryman, Sanjay Vashee, Radha Krishnakumar, Nacyra Assad-Garcia, Cynthia Andrews-Pfannkoch, Evgeniya A. Denisova, Lei Young, Zhi-Qing Qi, Thomas H. Segall-Shapiro, Christopher H. Calvey, Prashanth P. Parmar, Clyde A. Hutchison III, Hamilton O. Smith, and J. Craig Venter

A9   Synthetic Biology “From Scratch”

Gerald F. Joyce

A10 Manufacturing Molecules Through Metabolic Engineering

Jay D. Keasling

A11 Novel Approaches to Combat Biofilm Drug Tolerance

Kim Lewis

A12 Next-Generation Synthetic Gene Networks

Timothy K. Lu, Ahmad S. Khalil, and James J. Collins

A13 Engineering Scalable Biological Systems

Timothy K. Lu

A14 Metabolic Systems Biology

Bernhard Palsson

A15 Systems Vaccinology

Bali Pulendran, Shuzhao Li, and Helder I. Nakaya

A16 Solving Vaccine Mysteries: A Systems Biology Perspective

Lydie Trautmann and Rafick-Pierre Sekaly

A17 Systems Biology of Vaccination for Seasonal Influenza in Humans

Helder I. Nakaya, Jens Wrammert, Eva K. Lee, Luigi Racioppi, Stephanie Marie-Kunze, W. Nicholas Haining, Anthony R. Means, Sudhir P. Kasturi, Nooruddin Khan, Gui-Mei Li, Megan McCausland, Vibhu Kanchan, Kenneth E. Kokko, Shuzhao Li, Rivka Elbein, Aneesh K. Mehta, Alan Aderem, Kanta Subbarao, Rafi Ahmed, and Bali Pulendran

A18 Synthetic Systems as Microbial Threats: Predictability of Loss-of-Function Mutations in Engineered Systems

Sean C. Sleight, Bryan A. Bartley, and Herbert M. Sauro

A19 Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli

Parayil Kumaran Ajikumar, Wen-Hai Xiao, Keith E. J. Tyo, Yong Wang, Fritz Simeon, Effendi Leonard, Oliver Mucha, Too Heng Phon, Blaine Pfeifer, and Gregory Stephanopoulos

A20 Programming Cells: Towards an Automated ‘Genetic Compiler’

Kevin Clancy and Christopher A. Voigt

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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A21 Prokaryotic Gene Clusters: A Rich Toolbox for Synthetic Biology

Michael Fischbach and Christopher A. Voigt

A22 The Silicon Trypanosome

Barbara M. Bakker, R. Luise Krauth-Siegel, Christine Clayton, Keith Matthews, Mark Girolami, Hans V. Westerhoff, Paul A. M. Michels, Ranier Breitling, and Michael P. Barrett

B Agenda

C Acronyms

D Glossary

E Forum Member Biographies

F Speaker Biographies

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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WO-5   General conceptual framework for incorporating top-down and bottom-up perspectives in the synthetic biology design process

WO-6   Cost per base of DNA synthesis and sequencing

WO-7   Schematic presentation of directed evolution studies

WO-8   Breeding by DNA shuffling

WO-9   Principles of evolution

WO-10 Self-sustained amplification of a population of cross-replicating RNA enzymes, resulting in selection of the fittest replicators

WO-11 Is it alive? (no)

WO-12 Type III secretion system

WO-13 “Refactoring” gene clusters

WO-14 Phases and data used to generate a metabolic reconstruction

WO-15 XBP-1 target genes correlated to the maximum HAI response

WO-16 Schematic for theoretical construction of a generic vaccine chip

WO-17 CAMK4 expression on postvaccination day 3

WO-18 A framework for systems vaccinology

WO-19 Adoptive T-cell immunotherapy

WO-20 Clinical trial timeline on patient 5

WO-21 The effectiveness of T-cells based upon their functionality is reflected in this analogy

WO-22 Data showing the persistence of the population of engineered MART-1 antigen-specific CD8+ T-cells and the evolving functional performance of those cells

WO-23 Gyrase inhibitors induce an oxidative damage cellular death pathway

WO-24 A common mechanism induced by bactericidal antibiotics

WO-25 “Hello World” was the first image taken by the team at the University of Texas at Austin/UCSF with their photosensitive bacterial photographic “film” (this is a later, more polished version)

WO-26 Overview of steps in making a cell controlled by a synthetic genome

WO-27 Two-pronged attack strategy for biofilm removal with enzymatically active DspB-expressing T7DspB phage

WO-28 Targeting bacterial defense networks

WO-29A  Antibody discovery strategies

WO-29B  Isolation of monoclonal antibodies from responding patients

WO-30 A simple biofilm biosensor

WO-31 Cartoon describing Newcastle University 2010 iGEM team’s BacillaFilla

A1-1    Schematic of the Joule Unlimited Helioculture systems approach

A1-2    A summation of the accumulated photon losses for algal and direct fuel processes, as well as a theoretical maximum photonic energy conversion

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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A4-1    An electron micrograph of Staphylococcus aureus bacteria biofilms on the luminal surface of an indwelling catheter

A4-2    The engineering cycle as an approach for synthetic biology

A4-3    The principle and biological example of an AND gate

A5-1    Demonstration of the Edinburgh pH-based arsenic biosensor, Escherichia coli JM109/pSB1A2-BBa_J33203 with bromothymol blue as pH indicator, following static overnight incubation

A5-2    Detection of arsenic by B. subtilis 168/pTG262-arsR-xylE: absorbance at 377 nm vs. arsenic concentration (ppb arsenic as sodium arsenate)

A5-3    Altered response characteristics of a whole-cell arsenic biosensor through reassembly of the components

A5-4    Escherichia coli cells producing a variety of pigments

A7-1    Quorum sensing in Vibrio fischeri

A7-2    Diagram of the acyl-HSL quorum-sensing regulatory circuit in P. aeruginosa

A7-3    Some examples of acyl-HSL quorum-sensing signals

A8-1    The assembly of a synthetic M. mycoides genome in yeast

A8-2    Analysis of the assembly intermediates

A8-3    Characterization of the synthetic genome isolated from yeast

A8-4    Characterization of the transplants

A8-5    Images of M. mycoides JCVI-syn1.0 and WT M. mycoides

A10-1   Conversion of sugars to chemicals by means of microbial catalysts

A10-2   Use of synthetic regulators to modulate metabolic pathways that have a toxic intermediate

A10-3   The future of engineered biocatalysts

A11-1   Persisters and biofilms

A11-2   Resistance and tolerance

A11-3   A model of a relapsing biofilm infection

A11-4   The two faces of recalcitrance

A11-5   Candidate persister genes

A11-6   The HipA toxin causes dormancy in E. coli by phosphorylating elongation factor Tu, which inhibits protein synthesis

A11-7   Persister induction by antibiotic

A11-8   The high-tech platform

A11-9   A diffusion chamber for growing bacteria in situ

A11-10 Understanding the mechanism of uncultivability

A11-11 A high-throughput screen for antimicrobials in an animal model

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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A12-1   Tunable genetic filter

A12-2   Genetic signal converters

A12-3   Adaptive learning networks

A12-4   Amyloid-based memory

A12-5   Cell-cycle counter for biological containment

A12-6   Autonomous chemotaxis

A13-1   A basic design cycle for synthetic biology includes creating well-characterized parts (e.g., regulatory elements, genes, proteins, RNAs), constructing synthetic devices and modules and designing and assembling higher-order networks

A13-2   DNA sequencing and synthesis technologies are advancing at exponential rates, outpacing the ability of synthetic biologists to construct useful and scalable biological circuits

A13-3   Combinatorial high-throughput methods will be useful in the assembly of well-characterized libraries of synthetic parts and devices

A13-4   Control theory techniques for modelling synthetic biological circuits

A14-1   Growth of genome sequences and genome-scale metabolic reconstructions

A14-2   The four-step paradigm for metabolic systems biology

A15-1   Using systems biology to predict the immunogenicity of the YF-17D vaccine

A15-2   Systems biology approaches allow the identification of predictive gene signatures of immunogenicity for many vaccines

A15-3   Integrating systems biology approaches into clinical trials

A15-4   A framework for systems vaccinology

A16-1   Systems biology approaches in the vaccine development

A17-1   Analysis of humoral immunity to influenza vaccination

A17-2   Molecular signature induced by vaccination with LAIV

A17-3   Molecular signatures induced by vaccination with TIV

A17-4   Molecular signatures that correlate with titers of antibody to TIV

A17-5   Signatures that can be used to predict the antibody response induced by TIV

A17-6   CaMKIV regulates the antibody response to vaccines against influenza

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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A18-1   The T9002 genetic circuit

A18-2   Evolutionary stability dynamics of T9002 evolved under low-input (−AHL) and high-input (+AHL) conditions

A18-3   T9002 loss-of-function mutation

A18-4   T9002 reengineering

A18-5   Evolutionary stability dynamics of T9002 and reengineered T9002 circuits

A18-6   Loss of mutations in nine independently evolved populations

A18-7   Most common loss-of-function mutations in reengineered T9002 circuits

A18-8   Evolutionary half-life versus initial expression level in T9002 and T9002-E circuits evolved with different inducer concentrations

A19-1   Multivariate-modular approach for isoprenoid pathway optimization

A19-2   Optimization of taxadiene production through regulating the expression of the upstream and downstream modular pathways

A19-3   Fed-batch cultivation of engineered strains in a 1-liter bioreactor

A19-4   Engineering Taxol P450 oxidation chemistry in E. coli

A20-1   The compiler is focused on assembling the circuitry that links the inputs and outputs of a larger project

A20-2   A genetic compiler

A20-3   Semantics of genetic programs

A20-4   Automated program design using logic minimization algorithms

A20-5   Connecting genetic circuits

A21-1   Gene clusters encode organelles and molecular machines

A21-2   Gene clusters described in this review are compared

A21-3   Utilization and breakdown pathways encoded in gene clusters are shown

A21-4   Chemical production pathways are often encoded within gene clusters

A21-5   Complex regulatory pathways can be encoded by gene clusters

A22-1   The glycolytic pathway in Trypanosoma brucei

A22-2   The positive feedback from the ATP produced by glycolysis to the initial kinase reactions can lead to toxic accumulation of hexose phosphates

A22-3   The glycolytic and trypanothione pathways are linked through the oxidative pentose phosphate pathway

Suggested Citation:"Front Matter." Institute of Medicine. 2011. The Science and Applications of Synthetic and Systems Biology: Workshop Summary. Washington, DC: The National Academies Press. doi: 10.17226/13239.
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Many potential applications of synthetic and systems biology are relevant to the challenges associated with the detection, surveillance, and responses to emerging and re-emerging infectious diseases. On March 14 and 15, 2011, the Institute of Medicine's (IOM's) Forum on Microbial Threats convened a public workshop in Washington, DC, to explore the current state of the science of synthetic biology, including its dependency on systems biology; discussed the different approaches that scientists are taking to engineer, or reengineer, biological systems; and discussed how the tools and approaches of synthetic and systems biology were being applied to mitigate the risks associated with emerging infectious diseases.

The Science and Applications of Synthetic and Systems Biology is organized into sections as a topic-by-topic distillation of the presentations and discussions that took place at the workshop. Its purpose is to present information from relevant experience, to delineate a range of pivotal issues and their respective challenges, and to offer differing perspectives on the topic as discussed and described by the workshop participants. This report also includes a collection of individually authored papers and commentary.

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