proteomics: the next frontier---a biotech...

© 2004 Hindawi Publishing Corporation

Journal of Biomedicine and Biotechnology • 2004:3 (2004) 121–123 • PII. S1110724304404094 • http://jbb.hindawi.com

EDITORIAL

Proteomics: The Next Frontier—A BiotechPerspective

M. Walid Qoronfleh∗

Drug Discovery & Proteomics, Perbio Science, Bioresearch Division, Pierce Biotechnology, Inc,3747 N. Meridian Rd, PO Box 117, Rockford, IL 61105, USA

Proteomics is a nascent technology with much to de-velop and much to offer. Both the biotechnology andpharmaceutical arenas will be highly impacted by the newwindow proteomics is opening. This area of studies willpermit us to identify, characterize, and quantify proteinson a massive scale, resulting in a fundamental changein biological and chemical approaches to understandingproteins and even the ability to address new importantquestions. Advancing the tools of proteomic technologyfurther is of major interest to biotech and pharma com-munities. Proteomics does require substantial resourcesand infrastructure investment; therefore, the effort will begreatly enhanced by the coordinated participation of allinvolved, in both academia and industry. Such resourcesand coordination are only slowly becoming available onthe scale necessary to make a significant impact and theHuman Proteome Organization (HUPO) is at the van-guard of these efforts. The focus of this piece is on thepromises and the challenges of proteomics in biotech-nology, drug discovery, and diagnostics. Additional view-points from a business and scientific strategic standpointon where things are headed in the proteomics marketplacewill be discussed.

Now that the human genome has been sequenced, thestudy of the proteins that carry out the gene’s instructionis likely to be the next frontier in biomedical research.Surprisingly, the human genome appears to contain per-haps fewer than 30 000 genes, which is far fewer than theoriginal estimates. Enter the world of proteomics. Pro-teomics includes not only the identification and locationof proteins, but also the determination of networks, in-teractions, activities, and functions. A single gene can en-code multiple proteins through a variety of translationaland post-translational mechanisms. In addition, the sameprotein can assume multiple forms. Finally, the same pro-tein may have multiple functions, depending on its cel-lular environment and associated networks. All of thesepossibilities result in a proteome (the ensemble of proteins

related to a genome) estimated to be at least an order ofmagnitude more complex than the genome itself.

DRUG DISCOVERY

Drug discovery is a prolonged process that uses avariety of tools from diverse fields. Proteomics as an in-terdisciplinary field combines both biology and chemistryand the emerging areas of high-throughput automationand bioinformatics. Promising technologies, as part ofthe arsenal of proteomic techniques, are advancing theutility of proteomics in drug discovery process. The disci-pline of proteomics is currently divided into three distinctclasses that are indispensable to drug discovery: pro-filing proteomics, functional proteomics, and structuralproteomics. The tools in protein drug discovery rangefrom 2D/mass spec analyses to multiplex protein pro-filing to structure-based drug design. Vital to the func-tional/structural proteomics efforts are high-throughputcloning, protein expression, protein production, and pro-tein purification.

BIOTECHNOLOGY

Experimental studies related to protein fractionationand separation, qualitative and quantitative protein anal-yses, identification/characterization of the composition ofprotein complexes and organelles seem likely to enhanceour understanding of dynamic cellular processes, thus,making the proteome a less formidable challenge. Look-ing ahead we expect protein arrays to play a powerfulimportant role and that novel protein therapeutics willemerge.

Protein production

The challenge of studying proteins in a global wayis driving development of new technologies for system-atic and comprehensive analysis of protein structure and

122 M. Walid Qoronfleh 2004:3 (2004)

function. Experimental uses of proteins for structural andfunctional studies typically require milligram amountsin purified form. Protein expression, production, andpurification are fundamental processes in these stud-ies; however, they have typically only been applied ona case-by-case basis to proteins of interest. Strategies areemerging to industrialize these processes and overcomethe limitations imposed by conventional methods. Paral-lel processing, miniaturization approaches, array spottingtechniques all will significantly contribute to making pro-teomics more main stream.

Antibodies

To define the proteome of an organism, there is a needfor robust reproducible methods for the quantitative de-tection of all the polypeptides in a cell. Because of theirhigh-affinity, specificity, and their ability to bind virtuallyto any protein, antibodies appear particularly promisingas the receptor element in protein-detection arrays. Forproteomic-scale analyses and fabrication of high-densityarrays, the ability to produce and isolate antibodies enmasse to a large number of target molecules is critical. Thehigh-throughput issues of recombinant proteins applyequally well to antibody molecules to generate proteinsfor microarrays and antibodies for immunolocalizationand/or functional analysis utilizing highly sensitive detec-tion protocols.

DIAGNOSTIC

Biomarkers have been in widespread use for manyyears, but the field has emerged in its own right overthe last decade, propelled by proteomics. It is antici-pated that biomarker discovery will shift more to anal-ysis of biofluids and, to a lesser extent, tissue samplesfrom relevant patient populations as an initial approach.Furthermore, biomarker panels will be selected based ontheir prominence in discriminant analysis combined withtheir amenability to routine standardized clinical tests.Biomarkers derived from proteomics have the potentialto dramatically reduce both the time and the risk involvedin target discovery and validation, better understand dis-ease mechanisms (novel therapeutic modalities), diagnoseand track diseases and drug actions, and, finally, profilepatients for personalized medicine. Looking for biomark-ers/targets with the right tools in the right place shouldgreatly improve success rates and shorten the develop-ment cycle.

HUPO INITIATIVES

No discussion is complete without mentioning the ef-forts of HUPO and the various projects that are under-way. HUPO has galvanized the scientific community bothnationally and internationally to organize several humanproteome projects (plasma, liver, brain, etc), even a pilot

program for the mouse and rat liver proteome. Underthe patronage of HUPO academic labs, industrial partnersand regional HUPO societies soon will report significantadvances in protein science.

CONCLUDING REMARKS

Proteomics is changing the way we look at and dealwith proteins (diversity in structure, function, and dy-namic range). Various instrumentation advancementsand analytical tool improvements are a must to achievethe human proteome map. Many of the methods de-scribed in the literature were developed either as aproof-of-concept or as a pilot program in response tothe proteomic challenge. These technologies have beenproven to be able to deliver, to various degrees of course.The effectiveness of current or future methodologies willbe determined by resolving the many problems that willbe encountered. The success rate with “difficult” proteinswill be the true litmus test for any high-throughput, globalanalyses systems. It is unlikely that the processes in itscurrent form are going to meet the demand for profilingstructural or functional proteomic work. Improvementsare needed to gain economies of scale and efficienciesin protein manipulation. Parallel processing and genericmethods are required to achieve a systematic and thor-ough evaluation of protein function. The complexity ofthis effort is compounded by the large number of geneproducts comprising the proteome. At the end, sub-protein populations (subproteome) will become a com-modity, which can be delivered as a product rather thana service. This fundamental change is vital if the promisesof the proteome are to be realized.

The immediate impact of proteomics and the fruits ofproteomics are likely to be the following:

(1) proteomics will complement existing approaches todrug discovery/diagnostics,

(2) rewards of proteomics in early discovery efforts willbe realized 8–10 years of the typical drug develop-ment cycle,

(3) proteomic studies benefits will be seen sooner atlater-stage uses for drugs on or close to market(biomarkers for efficacy, toxicity, diagnostic, etc).

As final thoughts, it is hard to perceive that a certaintechnology or one system will dominate the landscape ofproteomics. Proteomics will become an integral compo-nent of systems biology to facilitate better-informed andearlier R&D decisions. Perhaps proteomics is like house-work, it will never end!

M. Walid Qoronfleh

2004:3 (2004) Editorial 123

M. Walid Qoronfleh earned an MS inChemistry from Illinois and a PhD inMicrobial Genetics from The Universityof Louisville Medical School. After post-doctoral work at the University of Geor-gia in molecular biology, he started hiscareer in the pharmaceutical industry in1989. Later, he received an MBA with anemphasis on R&D and technology man-agement from Penn State University. Asa scientist at SmithKline Beecham, he worked in the areas ofheterologous gene expression/protein engineering and studiedthe molecular aspects of HIV drug resistance. As a Sr. Sci-entist/Group Leader with Sterling-Winthrop Pharmaceuticals,he played a key role in the development of collagenases as atarget for HTS/structure-based drug design studies where theteam advanced two drug candidates. As a Scientist Managerin the Structural Biochemistry Program at the NCI his activi-ties focused on functional genomics, antivirals and anticancerswhere he was involved in target identification/validation and de-veloped assays to several enzymes. He established HT proteinexpression and protein purification capabilities for structure-based drug design efforts. As a Director of Antiinfective De-velopment at AntexPharma he established the company’s HTScapability and was responsible for hit-to-lead and lead opti-mization efforts. His efforts and the screens identified a broad-spectrum and specific agent antibiotics. Currently, he is theSenior Director for Drug Discovery & Proteomics at PerbioScience Bioresearch Division. He is engaged in various as-pects of proteomic research (methods or technology develop-ment). These efforts resulted in several commercial productsbeing available in the market place. He has 40 peer-reviewedpapers and over 50 published abstracts to his credit. He isa featured speaker at national and international conferences.Recently, M.W. Qoronfleh in collaboration with the MedicalCollege of Wisconsin in Milwaukee, University of Wisconsin-Madison, and other partners were awarded an NHLBI grant toestablish a proteomic center at MCW.

∗ E-mail: [email protected]

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