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Protein Arrays, Biochips and Proteomics: The Next Phase of Genomic Discovery PDF

355 Pages·2003·5.322 MB·English
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Protein Arrays, Biochips, and Proteomics The Next Phase of Genomic Discovery edited by Joanna S. Albala Lawrence Livermore National Laboratory Livermore, California, U.S.A. Ian Humpheiy-Smith University of Utrecht Utrecht, The Netherlands MARCEL - MARCELD EKKERIN,C . NEWY ORK BASEL DEKKER Copyright © 2003 by Marcel Dekker, Inc. Althoughgreatcarehasbeentakentoprovideaccurateandcurrentinformation,neither theauthor(s)northepublisher,noranyoneelseassociatedwiththispublication,shallbe liableforanyloss,damage,orliabilitydirectlyorindirectlycausedorallegedtobecaused bythisbook.Thematerialcontainedhereinisnotintendedtoprovidespecificadviceor recommendationsforanyspecificsituation. Trademarknotice:Productorcorporatenamesmaybetrademarksorregisteredtrademarks andareusedonlyforidentificationandexplanationwithoutintenttoinfringe. LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress. ISBN:0-8247-4312-1 Thisbookisprintedonacid-freepaper. Headquarters MarcelDekker,Inc.,270MadisonAvenue,NewYork,NY10016,U.S.A. tel:212-696-9000;fax:212-685-4540 DistributionandCustomerService MarcelDekker,Inc.,CimarronRoad,Monticello,NewYork12701,U.S.A. tel:800-228-1160;fax:845-796-1772 EasternHemisphereDistribution MarcelDekkerAG,Hutgasse4,Postfach812,CH-4001Basel,Switzerland tel:41-61-260-6300;fax:41-61-260-6333 WorldWideWeb http://www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the headquarters address above. Copyright2003byMarcelDekker,Inc.AllRightsReserved. Neitherthisbooknoranypartmaybereproducedortransmittedinanyformorbyany means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from thepublisher. Currentprinting(lastdigit): 10 9 8 7 6 5 4 3 2 1 PRINTEDINTHEUNITEDSTATESOFAMERICA Copyright © 2003 by Marcel Dekker, Inc. Foreword Duringtheleanyearsofproteomics,thefieldwaslargelydominatedbytechniques suchastwo-dimensionalgelelectrophoresis.Morerecently,thespectacularinno- vationsinmassspectrometryhavegivenproteomicsashotinthearmandtrans- formed the discipline. The complete sequencing of the human genome and that of other model organisms has further boosted proteomics in many ways, not leastbyprovidingasequence-basedframeworkforminingthehumanandother proteomes.Clearly,however,tomakeasubstantialimpactinbiomedicine,from disease-marker identification to accelerating drug development, proteomics has toevolvemuchfurtherinthedirectionofprovidinghigh-throughput,high-sensi- tivity, proteome-scale profiling. Unlike genomic-type profiling, which tends to be unidimensional, as exemplified by DNA microarrays that allow RNA abun- danceto bemeasured,there isaneed attheprotein leveltocapture amultitude ofproteinattributes.Thereisalsoaneedtodetermineinacellandtissuecontext not just the abundance of protein constituents but also their posttranslational modifications, aswell as their functionalstates and theirinteractions with other proteins and molecules, all with requisite high-throughput and high-sensitivity. The emerging field of protein biochips and microarrays is intended to address suchneedsandwilllikelymarkyetanotherevolutioninproteomics.Thestakes are high and the challenges are enormous. Themilestonesinanyemergingfieldsoonerorlaterincludethepublication ofbooksthatreviewprogressandprovidebothcriticalandforward-lookingper- spectives.ThisisthecaseforthistimelybookwiththecatchytitleProteinArrays, Biochips, and Proteomics: The Next Phase of Genomic Discovery. The editors have all the desired credentials and are well-suited for the task of assembling contributingauthorswhoareexpertsinthefield.Theeditorshavedevotedmuch iii Copyright © 2003 by Marcel Dekker, Inc. iv Foreword effort in their careers to activities that define the current status of protein chips and microarrays. They are very well connected and are prominently featured in meetings devoted to the subject. Commensurate with the need to assay a wide range of protein attributes, anequallywiderangeofchiptypeshavebecome availablethatarereviewedin thisbookwithrespecttotheirmeritsandlimitations.Innovativetechnologiesin this field have been developed by academics and by biotechnology companies, thuscontributingcreativesolutionstochallengingproblems.However,themost challengingproblemofall—deliveringcontentonaproteomescale—isbeyond thereachofbothacademicsandmostbiotechcompanies,simplybecauseofthe very high costs involved in producing the tens—and more likely hundreds—of thousands ofproteins encodedjust in thehuman genome,or to producecapture agents directed against these proteins and their various epitopes. A consortium approachnotunlikethatputtogetherforsequencingthegenomeorforcataloging genome-wide single-nucleotide polymorphisms may need to be implemented to meetthischallenge.Strategicconsiderationssuchasthesearebeingpursued,for example,bytheHumanProteomeOrganizationwithitsproteome-scaleantibody initiative. So what is in this book for the reader? Obviously, not all applications of protein chips need to be on a proteome scale. Much could be accomplished, particularlybyacademic investigators,throughfocusedapproaches thattargeta familyofproteins,aspecificsignalingpathway,oraparticularposttranslational modification. This book contains a wealth of information that brings the reader up to date in the field of proteomics, protein biochips, and array-based protein strategies,fromthetheoreticaltothepracticalaspects,withtopicsrangingfrom functionalizedchip surfacesand theperformance ofultrasensitiveligand assays using microarrays to strategies for expressing proteins. There is even a chapter thatreviewstheproteomicsmarketinitsvariousaspects.Thetextiseasytoread, asarethenumerousfiguresandchartsbefittingabookonchipsandmicroarrays. Itisrathergratifying toseethatthefieldof proteomicsnowencompasses chemical engineers, analytical chemists, biochemists, cell and molecular biolo- gists,clinicalscientists,andbioinformaticians,justtolistafewofthesubspecial- ties. I am confident that people in the field of proteomics or those who are contemplatingusingproteomics,howevervariedtheirinterests,willderivevalua- ble knowledge from reading this book. Sam Hanash President, Human Proteome Organization Professor of Pediatrics University of Michigan Ann Arbor, Michigan, U.S.A. Copyright © 2003 by Marcel Dekker, Inc. Preface Wasinger and colleagues (Electrophoresis, 1995, 16: 1090–1094) first defined the term proteome as: ‘‘the total protein complement able to be encoded by a given genome.’’ It is important to note that this encoded complement can vary significantly,temporally,andwithrespecttocellandtissuetype,whilethetem- poral variation can occur over very short time intervals. In an immunological context it is this antigenic diversity (temporal, cellular, and tissue-specific) that constitutesself.Acentraltenetofmodernimmunologyisthathealthyindividuals withdevelopinglymphocytesmustbeexposedtomostofself,soastoavoidthe dysfunctional state of autoimmunity. Thus, on a daily basis, the human body is faced with—and presumably succeeds at—the task of teaching developing lymphocytesthenatureofselfantigens,i.e.,thehumanproteomeinitsinnumera- bleiterations.Currently,however,experimentalproteomicsisfarfromachieving similaranalyticalsuccess;thetaskofaccessinganddetectingallelementswithin an entire mammalian proteome looms as an almost insurmountable charge, due mostly to the predominance of low-abundance gene products that continue to defydetection.Aproteomeofalivingcellororganismisahighlydynamicentity, andfollowingitsmanyfacetsinhealthanddiseaseconstitutesamajorchallenge to the biomedical and scientific community as we collectively attempt to build uponthewealthofunderstandingaffordedbycompletionoftheHumanGenome Project. A variety of technologies will be required to come to grips with this technological challenge. Herein, we have attempted to bring together authors at the forefront of theirdisciplinetoprovideanoverviewofcurrentandemergingtrendsandtheir applicationstothestudyof proteomics,particularlyarray-basedproceduresthat offer the promise of ‘‘near-to-total’’ proteomic screening in a high-throughput v Copyright © 2003 by Marcel Dekker, Inc. vi Preface microenvironmment,includinganalysisofcomplexmammalianproteomes,ina mannersimilartothatachievedforentiregenomesandtranscriptomes.Ofnote- worthy importance, however, are the associated financial and infrastructural re- sources likely to be required. They are no less daunting than was the initiation of the Human Genome Project more than a decade ago; the Human Proteome Project will require equally grandiose means on a global scale, if success is to be forthcoming over the next decade. For both the pharmaceutical industry and academics, the stimulus to proceed remains paramount in that it is the proteins, and not the nucleic acids, that are the molecular workhorses of the cell, that is, the physical players that decide physiological fates in action-packed scenarios with multiple possible endpoints more complex and perverse than the greatest suspensethrillerofAlfredHitchcockorAgathaChristie.Whethertheknivesand forksareemployedforabanquetoramassacredependsontheorderedpermuta- tionsofproteinisoforms,allofwhichawaitdecipheringwithintheinfiniteworld ofthemultidimensionalcomplexityassociatedwithintracellularmolecularinter- actions. The study of proteomics combines biochemistry, genetics, genomics, and molecularbiologytoexplorecellularnetworksinaparallelized,high-throughput, global format. Proteomics has its roots in protein profiling by two-dimensional gel electrophoresis and yet appears to some as a newcomer on the scientific scene, a logical next phase in genomic research. Because the nature of science isdynamic,thistextbookattemptstoaddressproteomicspast,present,andfuture. The aim is to present a variety of technologies and applications for proteomics research that will have broad application for the individual researcher and that should assist in the introduction of important concepts to newcomers. Thefirstfivechaptersfocusontheemergingtechnologyofproteinarrays and biochips in proteomic research and advances in their application to protein diagnosticsandtherapeutics.Chapters1and 2provideaglobaloverviewofthe emergingproteinarrayfieldaswellasathoroughhistoricalperspective.Chapters 3–5 expand on the details of generating and developing protein array technolo- gies. Chapters 6 and 7 explore array-based proteomics focusing on the use of resourcesfromgenomicstrategies,particularlyESTs(expressedsequencetags), cDNA databases, and robotics for generating protein content through high- throughputrecombinantexpressiontechniques.Thechapterthatfollowsexamines second-generationproteomicsanddescribesmethodsthatintegrateproteinprofil- ing by mass spectrometry with protein biochips. Chapter 9 describes shotgun proteomics applications using several mass spectrometry techniques. Chapters10and11examineanalysisofproteinfunction,specificallypro- tein–protein interaction assays, and explore unique applications in proteomics relatingvariousspecies,movingthroughthephylogenetictree,exemplifyinghow proteomicscanbeexploitedinmodelorganismsforapplicationtomorecomplex Copyright © 2003 by Marcel Dekker, Inc. Preface vii biologicalsystems.Chapter12exploresadvancesinstructuralproteomicsaimed atprovidingagreaterunderstandingofproteinbiochemistryandcellularfunction. Then,reflectinganageinwhichweareinundatedwithinformation,Chapter13 focusesontheintegrationofgenomicsandproteomicsinformation.Finally,Chap- ter 14 provides an educated insight into the growing proteomics market and its emerging biotech sector. This text aims to be the first to present a variety of genomic-based, high- throughputstrategiesforthestudyofproteinsbythescientistswhoaredefining proteomics.Itprovidesafoundationfromwhichtoexaminethefieldofproteo- mics as it evolves, to broaden our collective scientific outlook on the future direction of biological research. Joanna S. Albala Ian Humphery-Smith Copyright © 2003 by Marcel Dekker, Inc. Contents Foreword Sam Hanash iii Preface v Contributors xi 1. Protein Biochips and Array-Based Proteomics 1 Ian Humphery-Smith 2. Ultrasensitive Microarray-Based Ligand Assay Technology 81 Roger Ekins and Frederick Chu 3. Practical Approaches to Protein Microarrays 127 Brian Haab 4. Protein Biochips: Powerful New Tools to Unravel the Complexity of Proteomics? 145 Steffen Nock and Peter Wagner 5. Functionalized Surfaces for Protein Microarrays: State of the Art, Challenges, and Perspectives 159 Erik Wischerhoff 6. High-Throughput Protein Expression, Purification, and Characterization Technologies 173 Stefan R. Schmidt ix Copyright © 2003 by Marcel Dekker, Inc. x Contents 7. Miniaturized Protein Production for Proteomics 203 Michele Gilbert, Todd C. Edwards, Christa Prange, Mike Malfatti, Ian R. McConnell, and Joanna S. Albala 8. Protein Profiling: Proteomes and Subproteomes 217 Eric T. Fung and Enrique A. Dalmasso 9. Shotgun Proteomics and Its Applications to the Yeast Proteome 233 Anita Saraf and John R. Yates III 10. Forward and Reverse Proteomics: It Takes Two (or More) to Tango 255 David E. Hill, Nicolas Bertin, and Marc Vidal 11. Dynamic Visualization of Expressed Gene Networks 277 Ingrid Remy and Stephen W. Michnick 12. High-Throughput Structural Biology and Proteomics 299 Wuxian Shi, David A. Ostrov, Sue Ellen Gerchman, Jadwiga H. Kycia, F. William Studier, William Edstrom, Anne Bresnick, Joel Ehrlich, John S. Blanchard, Steven C. Almo, and Mark R. Chance 13. Integration of Proteomic, Genechip, and DNA Sequence Data 325 Leah B. Shaw, Vassily Hatzimanikatis, Amit Mehra, and Kelvin H. Lee 14. The Proteomics Market 337 Steven Bodovitz, Julianne Dunphy, and Felicia M. Gentile Copyright © 2003 by Marcel Dekker, Inc. Contributors Joanna S. Albala Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California, U.S.A. StevenC.Almo DepartmentofBiochemistry,AlbertEinsteinCollegeofMedi- cine, Bronx, New York, U.S.A. Nicolas Bertin Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, U.S.A. John S. Blanchard Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, U.S.A. Steven Bodovitz BioInsights, San Francisco, California, U.S.A. AnneBresnick DepartmentofBiochemistry,AlbertEinsteinCollegeofMedi- cine, Bronx, New York, U.S.A. Mark R. Chance Department of Physiology and Biophysics and Department ofBiochemistry,AlbertEinsteinCollegeofMedicine,Bronx,NewYork,U.S.A. FrederickChu MolecularEndocrinology,UniversityCollegeLondonMedical School, London, England Enrique A. Dalmasso Biomarker Discovery Center, Ciphergen Biosystems, Inc., Fremont, California, U.S.A. xi Copyright © 2003 by Marcel Dekker, Inc.

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