PerspectivesAre you interested in submitting a Perspective Article? Be sure to read The Science Advisory Board's Editorial Guides for Perspective Articles. Click here. Proteomics: Overview and Outlook by Deborah Fitzgerald The field of proteomics is organizing itself and gathering momentum by feeding on the energy of the genomics revolution and the sea of potential monetary profits. Proteomics researchers seek to analyze the total protein profiles of a given cell, organelle or tissue1-4. The goals are lofty, and the potential rewards are high. For example, the global pictures afforded by proteomics can provide insights regarding multiple factors involved in diseases, and may be exploited to identify new and better pharmaceutical targets. Although still a relatively young field, proteomics is rapidly growing due largely to the development, integration, and automation of requisite instrumentation, and the emergence of sophisticated bioinformatic techniques. One of the most common objectives of proteomic studies is the characterization of differences between protein expression levels of different samples (e.g., diseased versus non-diseased tissue). However, approaches for the global profiling of other properties of proteins, such as post-translational modification profiles or interactions with other biomolecules, are also becoming more commonplace. Contemporary proteomic techniques have incorporated innovative modifications to methods used for protein as well as genomic research. The first expression proteomics studies employed two-dimensional polyacrylamide gel electrophoresis (2DGE). Bolstered by continued application-specific protocol refinement, developments in technique and instrumentation, advances in imaging and bioinformatic technologies, 2DGE remains the most commonly used approach of today. Mass spectrometry (MS) has also become a staple of proteomics. MS-based approaches, often used in conjunction with database screening, allow relatively rapid protein identification after separation via 2DGE or alternative procedures. The ever-expanding arsenal of proteomic tools has also been supplemented with a variety of additional technologies, including global yeast two-hybrid screens, solution phase proteomic approaches, microarray-based assays, and a variety of bioinformatic tools. Indeed, the trend towards large-scale protein studies seems to be continually expanding to include new territories. For example, structural biologists are evaluating the use of high-throughput, robotic-aided versions of biophysical methods such as NMR spectroscopy and X-ray crystallography for proteomic studies.5 Ultimately, the goal of proteomics is to advance technology to a point at which a "protein signature" can be developed for any organism in a cost-effective manner using easily obtainable biological material. This is a daunting task considering that the identities and levels of a cell's constituent proteins, as well as their subcellular locations, form (e.g., post-translational modification or conformational state), and ultimately their activity or biofunctional statuses shift constantly in response to environmental changes, developmental state, or disease. But the solution to this riddle seems to lie in what may well become the watchwords of proteomics laboratories: dynamic, quantitative, and high-throughput. Most current proteomic methods focus on taking a static snapshot of all cellular proteins at one point in time. However, some proteomics pioneers are focusing on developing methods for dynamically and quantitatively studying proteomic shifts that occur in response to changes in the cell's environment or in healthy versus diseased cells. These promising technologies include isotopic labeling followed by MS detection to quantitatively compare global protein expression in cells and tissues, as well as the coupling of affinity purification methods with MS techniques. Improved bioinformatic technologies will also be crucial for proteomics studies of the future. Researchers will need more sophisticated protein databases to make sense of their own proteomics data. Further, data from different types of proteomic studies will need to correlated, as well as integrated with results from genomic approaches. Proteomic approaches may prove to be a great boon to the pharmaceutical industry by increasing the scale of drug discovery research and potentially reducing the time to market for new drugs with protein targets. These types of studies can also be used to delve into the fundamentals of cell function, such as further characterizing the complex interplay between different signaling pathways. Indeed, proteomics has become quite the buzzword in today's academic and corporate research laboratories alike, and many are hopeful that it will succeed the Human Genome Project as the next "Big Science" project of this millennium. Others have expressed some doubts about the feasibility of conducting truly global studies of proteins, which are remarkably heterogeneous subset of biomolecule. Regardless, the hubbub and excitement surrounding proteomics suggests that we may anticipate the continued evolution of this field, as well as forthcoming contributions to the life and health sciences. References
### Deborah Fitzgerald, a member of The Science Advisory Board, holds a doctorate in biochemistry and is a freelance biotechnology writer and consultant based in Birmingham, Alabama. ### Next >> [ View All Perspectives ] |
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