Proteomics Q. and A.

A. The foundation of the Proteomics Research and Development Facility was primarily enabled through a portion of funds from INGEN that were directed to the Bloomington campus. The INGEN-originated funds are supporting a purchase of major pieces of equipment for proteomics measurements as well as research activities. Basically, our mission is (a) to enhance collaboration with biomedical scientists at the IU School of Medicine and Bloomington science departments in the use of research proteomics; and (b) to develop new types of equipment for future investigations in the field.

Q. What are your collaborative efforts now?

A. Our efforts now range from working on bacterial and fruit fly proteomes with the biology faculty to animal models of alcohol dependency and diabetes, cancer cells and human samples with the School of Medicine faculty.

Q. Can you tell us more about proteomics, which I understand is a relatively new term?

A. The more recent developments in recombinant DNA technologies and other biological techniques have endowed scientists with the unprecedented power of expressing proteins in large quantities, in a variety of conditions, and in manipulating their structures. While scientists were usually accustomed to studying proteins one at a time, proteomics represents a comprehensive approach to studying the total proteomes of different organisms. Thus, proteomics is not just about identification of proteins in complex biological systems, a huge task in itself, but also about their quantitative proportions, biological activities, localization in the living cells and their small compartments, interactions of proteins with each other and with other biomolecules. And ultimately, their functions. Because even the lower organisms can feature many thousands of proteins, proteomics-related activities are likely to keep us busy for two or three decades.

Q. You are a biochemist. What is the connection in proteomics between biology and chemistry?

A. With the boundaries between traditional scientific disciplines blurring all the time, this is somewhat difficult to answer. While proteomics has some clear connections to modern biological research, its current research tools and methodologies are chemical, some might even say, physio-chemical. You prominently see there are large, sophisticated machines like mass spectrometers, which in some parts of the world are still considered within the ‘physics domain.’ But things are continuously changing in this dynamic field. Genomic research, a distinct area of modern biology, has significantly changed the way in which we view the task of various proteomes.

Q. What has changed in the past five or so years?

A. The field of genomics, with its major emphasis on sequencing the basic building blocks of the ‘central molecule,’ DNA, already has yielded highly significant information on the previously unknown secrets of living cells. The stories of newly discovered genotype-phenotype relationships and strategies for understanding genetic traits and genetic diseases now regularly flood top scientific journals and popular literature alike. In parallel with providing the blueprint of the human genome, the genomes of many bacterial species, yeast and fruit flies for instance, have been sequenced, providing a valuable resource for modern biomedical research. The mouse genome also has been completed recently. Likewise, in the area of plant sciences, some important genomic advances have been reported. Yet, only a part of genetic information is of a direct use to proteomics.

Q. How is that?

A. While the entire protein sequences are encoded in the respective genomes, numerous variations occur as well. Some proteins may remain intact as the direct products of genes, but most will undergo structural alterations due to a variety of epigenetic factors. Thus, a given proteome is not merely a protein complement dictated by a genome, but rather a reflection of the dynamic situations in which different cells express themselves under various conditions of their environment. Here lie some of the most challenging problems of contemporary proteomics—to understand the dynamics, altered structural and quantitative attributes of proteins and their effects on metabolic pathways.

Q. Proteomics seems like a huge area of study with many avenues to research. What are you and your colleagues at IU focusing on?

A. While proteomics is becoming a fiercely competitive field, the tools and methodologies are still under considerable development. The Bloomington proteomics group has a distinct advantage over most competing institutions in that our faculty have been among the world leaders in pushing the proteomics tools toward higher analysis throughput and greater measurement sensitivity for less abundant, albeit not unimportant, proteins. We have the proven capability of building new types of equipment that should keep us at the cutting edge of methodology—in summary, faster and more information-rich techniques.

Q. So technology development is an IU strength. What other areas are you working in?

A. Many proteins must become post-translationally modified to fulfill their biological roles. To assess such modifications, in a qualitative and quantitative sense, is thus at the heart of this field. Fortunately, we have been active for a number of years in studying one of the most prevalent and perhaps the most important posttranslational modification, called “glycosylation,” which is the attachment of complex carbohydrate molecules to selected sites on a protein. Glycosylation is now being increasingly implicated in a number of disease-related conditions, including cancer, cardiovascular disease, neurological disorders and a great number of other medically interesting conditions.

Also, in collaboration with members of the medical faculty in Indianapolis, we will investigate the molecular attributes of human diseases. Studying the proteomics of highly complex multicellular systems of mammals provides some unusually exciting opportunities and challenges.

Proteomics is bound to become a more ‘quantitative science’ in the future. Unlike with the negatively charged nucleic acids that are relatively easy to handle in solutions and on surfaces, many proteins suffer from surface interactions and consequently, poor recoveries. We certainly wish to improve acquisition of the quantitative profiles of proteins for different protein classes.

Q. What are some practical applications of proteomics research?

A. Due to the multilateral importance of proteins in living systems, the scope of biomedical application is apparently wide. In fine-tuned functioning of the human body, various proteins act as the catalysts of chemical reactions, cell growth mediators, molecular transporters and receptors, immune agents against microorganisms and more. Consequently, various human diseases manifest themselves in the altered concentrations or structures of proteins, so that finding protein markers of a disease can, for example, result in devising better means of diagnosis or follow-up therapy. Numerous proteins have now been used therapeutically, so that there have to be perfect ways of manufacturing quality control for such therapeutics, or even to trace their action in the human body. Pharmaceutical companies, thus, have considerable interest in proteomics. Various activities in this area also provide considerable stimulus to the instrument industry. Consequently, coming up with new ways and better means to analyze complex protein mixtures is a high priority. These are just a few examples of how proteomics can impact our future.