‘The future is molecular medicine butwhen?’ This is the question that John Todd(University of Cambridge, UK) asked at thebeginning of his keynote lecture of theProtein to Profits conference held in Munich,Germany on 24–25 April 2003. Hispresentation opened the second annualmeeting on recent ideas and technicaldevelopments in the wide-ranging field ofproteomics research.The organizers of themeeting, the Cambridge Healthtech Institute(http://www.healthtech.com), avoidedfocusing exclusively on technology andbrought together a panel of speakers whoaddressed current advances in technologyin addition to the requirements of thepharmaceutical industry.

From genotype to phenotypeThe opening presentation by Todd (one ofthe organizers) focused on polymorphismsof the human genome and illustrated howgenetic analysis can provide insight intoprimary disease mechanisms. Following thepublication of recent studies on geneticfactors and susceptibility to autoimmunedisease [1],Todd was able to make a strong case for the identification of causaldisease pathways by linking genotype todisease phenotype. However, he also made it clear that the availability of suchadvanced technology today has not resultedin the breakthrough that everyone washoping for, and it will take time to get a gripon the enormous wealth of data that hasbeen generated.

In a second keynote lecture, Massimo deFrancesco (Serono Pharmaceutical ResearchInstitute; http://www.serono.com) addressedthe importance of proteome research froma different angle.The process of finding new

pharmaceutical therapeutics is a complextask and the employment of newproteomics technologies will enableresearchers to ‘industrialize cell biology’.Although this will add layers of complexity,it will be a paradigm shift not only in drugdevelopment but also in biology.‘Beexhaustive’ was de Francesco’s statementand by introducing relevant high-contentassays this aim seems to be within reach.

So, right from the beginning of the meetingthe tone was set and it was clear that thetasks are enormous and the requirementsare high. Nevertheless, there are solutionsand the first session on ‘Protein Structureand Interactions’ gave examples of what ispossible. Peter Uetz introduced the two-hybrid system as a screening tool forprimary drug target identification. In hislaboratory at the ForschungszentrumKarlsruhe, Germany (http://www.fzk.de)automated systems are established that arehighly flexible and employ random anddirected approaches to analyse the broadspectra of protein–protein interactions.

Ulf Skoglund [Karolinska InstituteStockholm (http://www.info.ki.se) and Sidec™ Technologies AB(http://www.sidectech.com)] uses electrontomographic methods to analyse proteinsand protein complexes. During hispresentation, impressive pictures of proteinsin their native environment were shown;membrane proteins within the membranewere visualized at a resolution 2–3 nm inthree dimensions, without the need of acomplex sample preparation.The realities ofdrug development (with respect to costsand time) were brought to the audience’sattention by Ismail Moarefi (SiREEN AG;http://www.sireen.de/). Focusing on the

action of small-molecule inhibitors withinsignal transduction networks, researchers atSiREEN (signal recognition engineering)generated a structure-based approach toscan for target-specific inhibitors – breakingdown the complexity of biological systemsby looking at the specificity and selectivityof a drug on a selected target family.

The second focus of the meeting‘Proteome Profiling’ was first addressed by Keith Rose from GeneProt(http://www.geneprot.com).The Swisscompany uses highly automated and highlysensitive mass spectrometry methods toanalyse complex samples to identify markersand targets for specific disease conditions.As an example of the remarkable workdone at GeneProt, the characterization ofhuman plasma from patients with coronaryheart disease was shown. During hispresentation Rose addressed questions ofautomation, data management andinterpretation.These are key topics for allproteomics approaches and thereforeseveral of the following presentationsaddressed these questions. Peter J. Boogaard(Applera; http://www.applera.com) made itclear that without powerful informaticstools the amount of data generated by theglobal approaches is not manageable, and hepresented the software tools developed byApplera. An integrated platform developedto make biological sense of the acquireddata was presented by Mathias Göschl (LionBioscience; http://www.lionbioscience.com).The platform, called TargetEngine™, notonly links a variety of different databasescontaining biologically relevant data, but it visualizes connections and therefore helps to identify interrelations that are not obvious.

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Drug development in the era ofproteomicsStefan Kramer and Markus F. Templin*, NMI – Natural and Medical Science Institute at the University of Tübingen, Markwiesenstr. 55, 72770 Reutlingen,Germany, *e-mail: templin@nmi.de

Protein microarraysMathias Uhlen from the Royal Institute ofTechnology in Stockholm ended the first daywith an overview of what an integratedproteomics approach that analyses thefunction of each single gene of the humangenome might look like.The problems Uhlenaddressed were manifold. How can theproteins that are encoded by the genes befound? Where are the proteins? Howabundant are the proteins? Are the proteinscorrelated with certain disease states? Thus, it is clear that there are many proteinsand many questions. However, Uhlen cameup with a straightforward approach: useantibodies and use arrays.This approachseems feasible and is used at the RoyalInstitute of Technology in Stockholm(http://www.biotech.kth.se/molbio/hpr/index.html). Uhlen’s presentation showed thatarray-based technologies will play a key rolein proteomics research and, consequently,an extended session on protein microarraysfollowed. Dolores Cahill (Max PlanckInstitute for Molecular Genetics, Berlin;http://www.molgen.mpg.de) presented adifferent approach to analyse the wholehuman proteome. Starting from a complexexpression library, fusion proteins weregenerated and used to make arrays

consisting of several thousands of differentspots, each representing a different protein.In different examples Cahill showed thatthese arrays are powerful tools to examinedifferent disease states.Technology isimportant for the miniaturized systemsemployed and the reports from EmmanuelDelamarche (IBM Zürich ResearchLaboratory; http://www.zurich.ibm.com)showed the use of soft lithography printingtechniques and microfluidic networks tocreate ultrafast micromosaic immunoassays,and Jennifer Brockman (HTS Biosystems;http://htsbiosystems.com) reported thepossibility of using the label-free plasmonresonance technology in combination withmicroarrays.Volker Vogel (Qiagen;http://www.qiagen.com) reported on theall-important topic of automation andpresented a high-capacity system builtaround the bead-based Luminex technology.This focus on technology made it clear thatthe advances are substantial and that a lot ofthe technological innovations of recent yearstranslated into useful products.

Drug discoveryThe conference concluded with twohighlights, a clear statement on theexpectations of the pharmaceutical industry

and an example of how novel ideas can betranslated into a powerful technology thatwill meet these demands.The lecture byJan-Anders Karlsson (Executive VicePresident, Pharma Research, Bayer AG;http://www.bayer.de) focused on the needfor the discovery of novel and more effectivemedicines. High-throughput technologiesand additional protein-based methods andstrategies are required and will enable theidentification of high-quality drugs in thepost-genome era. Giulio Superti-Furga(Vice President, Cellzome AG;http://www.cellzome.com) showed thatsome biotech companies are able toaccomplish these difficult tasks. Indeed,Cellzome’s proteomics approach toidentifying druggable targets has proven tobe very efficient. By detecting direct physicalinteractions between proteins, new targetscan be identified and disease pathways can bevalidated.Thus, the conference ended with avery impressive example that demonstratedthe impact of proteomics research and howthe drug discovery process is changing.

Reference1 Ueda, H. et al. (2003) Association of the T-cell

regulatory gene CTLA4 with susceptibility to

autoimmune disease. Nature 423, 506–511

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Contributions to TARGETS

TARGETS reviews advances in genomics and proteomics that will impact on drug and target discovery. Coverage includes new drug targetsin a therapeutic area; new classes of target; new and emerging technologies; new applications of existing technologies; and updateson the progress of gene sequencing projects and the Human Proteome Project.

Authors should aim for topicality rather than comprehensive coverage. Ultimately, articles should improve the reader’s understanding ofthe field addressed, and enable them to keep abreast of the latest advances and trends.

Please note that publication of Review articles is subject to satisfactory expert peer and editorial review.The publication of Update andEditorial articles is subject to satisfactory editorial review. In addition, personal perspectives published in TARGETS do not represent theview of the journal or its editorial staff

If you would like to contribute to the Reviews, Update and Editorial sections of TARGETS in the future, please submit your proposals to:Dr Joanna Owens, Editor (e-mail:TARGETS@drugdiscoverytoday.com).