Copyright © National Academy of Sciences. All rights reserved. Transforming Glycoscience: A Roadmap for the Future Transforming Glycoscience: A Roadmap for the Future Committee on Assessing the Importance and Impact of Glycomics and Glycosciences Board on Chemical Sciences and Technology Board on Life Sciences Division on Earth and Life Studies THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu Copyright © National Academy of Sciences. All rights reserved. Transforming Glycoscience: A Roadmap for the Future PREPUBLICATION COPY 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. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This project was supported by the National Institutes of Health under contract N01-OD- 4-2139, TO#251, the National Science Foundation under grant CHE-1138764, the U.S. Department of Energy under contract DE-SC0007069, the Food and Drug Administration under contract HHSF223200810020I, TO#HHSF22301023, and the Howard Hughes Medical Institute. The views expressed herein are those of the authors and do not necessarily reflect the views of the organizations or agencies that provided support for the project. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Library of Congress Cataloging-in-Publication Data or National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, D.C. 20055, (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet <http://www.nap.edu>. Copyright 2012 by the National Academy of Sciences. All rights reserved. Printed in the United States of America 978-0-309-26083-1 International Standard Book Number Copyright © National Academy of Sciences. All rights reserved. Transforming Glycoscience: A Roadmap for the Future PREPUBLICATION COPY 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 Copyright © National Academy of Sciences. All rights reserved. Transforming Glycoscience: A Roadmap for the Future Copyright © National Academy of Sciences. All rights reserved. Transforming Glycoscience: A Roadmap for the Future v PREPUBLICATION COPY COMMITTEE ON ASSESSING THE IMPORTANCE AND IMPACT OF GLYCOMICS AND GLYCOSCIENCES DAVID WALT (Chair), Department of Chemistry, Tufts University KIYOKO F. AOKI-KINOSHITA, Department of Bioinformatics, Soka University, Japan BRAD BENDIAK, University of Colorado, Denver CAROLYN R. BERTOZZI, University of California, Berkeley GEERT-JAN BOONS, Complex Carbohydrate Research Center, University of Georgia ALAN DARVILL, Complex Carbohydrate Research Center, University of Georgia GERALD HART, Department of Biological Chemistry, Johns Hopkins University School of Medicine LAURA L. KIESSLING, Department of Chemistry, University of Wisconsin JOHN LOWE, Genentech, Inc. ROBERT MOON, Forest Products Laboratory, U.S. Forest Service JAMES C. PAULSON, Departments of Chemical Physiology and Molecular Biology, The Scripps Research Institute RAM SASISEKHARAN, Massachusetts Institute of Technology AJIT P. VARKI, Glycobiology Research and Training Center, University of California, San Diego, School of Medicine CHI-HUEY WONG, Academia Sinica, Taiwan, and The Scripps Research Institute Staff KATHERINE BOWMAN, Co-Study Director and Senior Program Officer, Board on Life Sciences DOUGLAS FRIEDMAN, Co-Study Director and Program Officer, Board on Chemical Sciences and Technology SHEENA SIDDIQUI, Senior Program Associate, Board on Chemical Sciences and Technology RACHEL YANCEY, Senior Program Assistant, Board on Chemical Sciences and Technology JOE ALPER, Consulting Science Writer Copyright © National Academy of Sciences. All rights reserved. Transforming Glycoscience: A Roadmap for the Future vi PREPUBLICATION COPY BOARD ON CHEMICAL SCIENCES AND TECHNOLOGY PABLO G. DEBENEDETTI (Co-Chair), Princeton University C. DALE POULTER (Co-Chair), University of Utah ZHENAN BAO, Stanford University ROBERT BERGMAN, University of California, Berkeley HENRY E. BRYNDZA, E. I. du Pont de Nemours & Company EMILY CARTER, Princeton University DAVID CHRISTIANSON, University of Pennsylvania MARY JANE HAGENSON, Chevron Phillips Chemical Company LLC CAROL J. HENRY, Independent Consultant JILL HRUBY, Sandia National Laboratories MICHAEL C. KERBY, ExxonMobil Chemical Company CHARLES E. KOLB, Aerodyne Research, Inc. JOSEF MICHL, University of Colorado, Boulder SANDER G. MILLS, Merck, Sharp, & Dohme Corporation DAVID MORSE, Corning, Inc. ROBERT E. ROBERTS, Institute for Defense Analyses DARLENE J. S. SOLOMON, Agilent Technologies JEAN TOM, Bristol-Myers Squibb DAVID WALT, Tufts University Staff DOROTHY ZOLANDZ, Director TINA MASCIANGIOLI, Senior Program Officer KATHRYN HUGHES, Program Officer DOUGLAS FRIEDMAN, Program Officer AMANDA CLINE, Administrative Assistant SHEENA SIDDIQUI, Senior Program Associate RACHEL YANCEY, Senior Program Assistant Copyright © National Academy of Sciences. All rights reserved. Transforming Glycoscience: A Roadmap for the Future vii PREPUBLICATION COPY BOARD ON LIFE SCIENCES JO HANDELSMAN (Chair), Yale University, California, New Haven, Connecticut VICKI L. CHANDLER, Gordon and Betty Moore Foundation, Palo Alto, California SEAN EDDY, HHMI Janelia Farm Research Campus, Ashburn, Virginia SARAH C.R. ELGIN, Washington University, St. Louis, Missouri DAVID R. FRANZ, Former Cdr USAMRIID, Frederick, Maryland LOUIS J. GROSS, University of Tennessee, Knoxville, Tennessee RICHARD A. JOHNSON, Arnold & Porter, LLC, Washington, D.C. JUDITH KIMBLE, University of Wisconsin, Madison, Wisconsin CATO T. LAURENCIN, University of Connecticut Health Center, Farmington, Connecticut ALAN I. LESHNER, American Association for the Advancement of Science, Washington, D.C. BERNARD LO, University of California, San Francisco, California KAREN E. NELSON, J. Craig Venter Institute, Rockville, Maryland ROBERT M. NEREM, Georgia Institute of Technology, Atlanta, Georgia CAMILLE PARMESAN, University of Texas, Austin, Texas ALISON G. POWER, Cornell University, Ithaca, New York MARGARET RILEY, University of Massachusetts, Amherst, Massachusetts BRUCE W. STILLMAN, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York JANIS C. WEEKS, University of Oregon, Eugene, Oregon CYNTHIA WOLBERGER, Johns Hopkins University School of Medicine, Baltimore, Maryland MARY WOOLLEY, Research!America, Alexandria, Virginia STAFF FRANCES E. SHARPLES, Director JO L. HUSBANDS, Scholar/Senior Project Director JAY B. LABOV, Senior Scientist/Program Director for Biology Education KATHERINE W. BOWMAN, Senior Program Officer INDIA HOOK-BARNARD, Senior Program Officer MARILEE K. SHELTON-DAVENPORT, Senior Program Officer KEEGAN SAWYER, Program Officer BETHELHEM M. BANJAW, Financial Associate ORIN E. LUKE, Senior Program Assistant CARL G. ANDERSON, Program Associate SAYYEDA AYESHA AHMED, Senior Program Assistant Copyright © National Academy of Sciences. All rights reserved. Transforming Glycoscience: A Roadmap for the Future Copyright © National Academy of Sciences. All rights reserved. Transforming Glycoscience: A Roadmap for the Future ix PREPUBLICATION COPY Preface Although I was trained as a synthetic organic chemist and was involved in carbohydrate research early in my scientific career, my research has primarily been focused on developing new technologies for making analytical measurements. This work has led to the development and commercialization of some of the technologies that are presently used for the revolution in genetics and genomics that has taken place over the past decade. I have seen the transformation in scientific capability enabled by these new genetic tools. Access to both the tools and the public databases by virtually any scientist and engineer has democratized the field and has made genetic information an essential component of many fields of science. Science has benefitted tremendously, and many fields are decades ahead of where they would have been without these capabilities. In addition, genetic technologies are beginning to have a big impact on practical applications—diagnostics, therapeutics, and animal breeding to name a few. The economic benefit is in the billions of dollars per year and growing. This study can be viewed as an opportunity to elevate the importance and possibilities of glycoscience, which is equally pervasive and certainly more directly linked to biological activity than genetics. For example, glycans are responsible for virtually all cell-cell recognition. Moreover, they play a central role in recent burgeoning biofuels efforts. But glycoscience has much more to offer, as described in this report. It was identifying these opportunities and providing a roadmap that was the challenge to the Committee on Assessing the Importance and Impact of Glycomics and Glycosciences. The National Academies assembled a stellar group of glycoscientists for this committee. They came from disparate fields—biology, chemistry, and computer science—and work on equally diverse problems in fundamental biology, synthetic chemistry, health, energy, and materials science. I have been so impressed with the passion of these glycoscience committee members for their field. They have worked for many years to advance this important yet underappreciated area—and, despite my limited knowledge of the field, they welcomed me both as a colleague and a friend. It has been a genuine pleasure to work with this dedicated and passionate group of scientists. They have worked tirelessly to help advance the field and, more importantly, science in general with their contributions to this study and to this report. The community is indebted to their service. The National Academies staff are the real heroes. In particular, Dr. Katherine Bowman and Dr. Douglas Friedman were essential to the success of this study. Katie and Doug pushed the committee to meet deadlines, dealt with the challenging logistics of committee members spanning 12 time zones, helped pull the report together, and worked tirelessly. Even with difficult deadlines, I never heard them complain. They brought ideas and creativity to the discussions. Their selfless dedication to science is admirable and should be a model for us all. In addition to Katie and Doug, Sheena Siddiqui and Rachel Yancey provided superb administrative support. I also want to thank Dr Fran Sharples, director of the Board on Life Sciences, and Dr. Dorothy Zolandz, director of the Board on Chemical Sciences and Technology, for their support and vision. This report has the potential to transform the field of glycoscience, but—more significantly—it should transform science in dramatic ways. Sugars are ubiquitous, and scientists in all fields will realize the full potential of their research only by embracing and incorporating glycoscience. The tools for realizing this potential are not available yet. It is [...]... used as important materials for example, as gelling agents in foods—and as a renewable resource for high-value chemicals, plastics, and 16 PREPUBLICATION COPY Copyright © National Academy of Sciences All rights reserved Transforming Glycoscience: A Roadmap for the Future pharmaceuticals Wood, comprised of lignocelluloses, is a major building material and is used in myriad applications Other materials,... results of achieving these goals have the potential to impact science in exciting ways 9 PREPUBLICATION COPY Copyright © National Academy of Sciences All rights reserved Transforming Glycoscience: A Roadmap for the Future Copyright © National Academy of Sciences All rights reserved Transforming Glycoscience: A Roadmap for the Future 1 Introduction 1.1 UNDERSTANDING THE LANGUAGE OF LIFE: THE CENTRALITY... glycans and of plant cell wall construction and deconstruction, glycoscience can play an important role in the development of non-petroleum-based sustainable new materials Glycan-based materials have wide-ranging uses in such areas as fine chemicals and feedstocks, polymeric materials, and nanomaterials There are many pathways to create a variety of functionalities on a glycan, creating a wide range... carbohydrates and glycoconjugates, be established as a collaborative effort by all stakeholders The carbohydrate structural database needs to be fully cross-referenced with databases that provide complementary biological information (e.g., PDB and GenBank) Furthermore, there should be a requirement for deposition of new structures into the database using a reporting standard for minimal information Roadmap Goals... in their work Within 5 years, employ an active curation system to automatically validate glycan structures deposited into a database so that journals can provide authors with an easily accessible interface for submitting new glycan structures to the database To achieve the roadmap goals articulated in its recommendations, the committee notes that it will be of critical importance for the field to reach... reserved Transforming Glycoscience: A Roadmap for the Future SUMMARY In response to a request from the National Institutes of Health (NIH), the Food and Drug Administration (FDA), the U.S Department of Energy (DOE), and the National Science Foundation (NSF), the National Research Council convened a committee to assess the importance and impact of glycoscience, explore the landscape of current research, and.. .Transforming Glycoscience: A Roadmap for the Future the hope of the committee that this report will bring glycoscience into the scientific mainstream David Walt, Chair Committee on Assessing the Importance and Impact of Glycomics and Glycosciences x PREPUBLICATION COPY Copyright © National Academy of Sciences All rights reserved Transforming Glycoscience: A Roadmap for the Future Acknowledgments... with the authors and the institution xi PREPUBLICATION COPY Copyright © National Academy of Sciences All rights reserved Transforming Glycoscience: A Roadmap for the Future Copyright © National Academy of Sciences All rights reserved Transforming Glycoscience: A Roadmap for the Future Contents SUMMARY 1 1 Introduction .11 1.1 Understanding the Language of Life: The Centrality... options for tailoring material properties Based on the above, the committee makes the following findings regarding the toolkit needed to advance glycoscience: Scientists and engineers need access to a broad array of chemically well-defined glycans 5 PREPUBLICATION COPY Copyright © National Academy of Sciences All rights reserved Transforming Glycoscience: A Roadmap for the Future Over the past 30 years,... integrated and centralized manner similar to other biological information A ROADMAP TO ADVANCE GLYCOSCIENCE Based on these findings, the committee makes the following recommendations in order to achieve a more complete understanding of glycoscience and to realize its impacts on health, energy, and materials science Each recommendation is followed by a series of roadmap goals The capabilities created by the achievement . National Academy of Sciences. All rights reserved. Transforming Glycoscience: A Roadmap for the Future Transforming Glycoscience: A Roadmap for the Future Committee on Assessing. reserved. Transforming Glycoscience: A Roadmap for the Future Copyright © National Academy of Sciences. All rights reserved. Transforming Glycoscience: A Roadmap for the Future 1 PREPUBLICATION. reserved. Transforming Glycoscience: A Roadmap for the Future ix PREPUBLICATION COPY Preface Although I was trained as a synthetic organic chemist and was involved in carbohydrate research early