PROTEOMICS
The proteome is the protein complement of the genome . It is quite a bit more complicated than the genome because a single gene can give rise to a number of different proteins through alternative splicing of the pre-messenger RNA RNA editing of the pre-messenger RNAs
attachment of carbohydrate residues to form glycoproteins.
The dream of having genomes completely sequenced is now a reality. The complete sequence of many genomes including the human one is known. However, the understanding of probably half a million human proteins encoded by less than 30 000 genes is still a long way away and the hard work to unravel the complexity of biological systems is yet to come.
A new fundamental concept called proteome (PROTEin complement to a genOME) has recently emerged that should drastically help to unravel biochemical and physiological mechanisms of complex multivariate diseases at the functional molecular level. The discipline of proteomics has been initiated to complement physical genomic research. Proteomics can be defined as the qualitative and quantitative comparison of proteomes under different conditions to further unravel biological processes.
Proteomics is the study of all the proteins that make up an organism. Proteomics doesn t just study the proteins themselves, but also the way they interact, the changes that they undergo, and the effects that they have within the organism. The size and complexity of the human proteome is part of what makes proteomics a very complex science.
Proteomics is the large-scale study of proteins, particularly their structures and functions. The term was coined to make an analogy to genomics (the study of genes and the gene code), and together these technologies are often considered the "next step," in clinical diagnostics. Proteomics, however, is much more complicated than genomics. There are far fewer genes that code for proteins in the human genome than there are proteins in the human proteome (~22,000 genes vs. ~300,000 proteins).
And while the genome is a relatively constant entity, the proteome is constantly changing through its biochemical interactions with the genome and with other proteins. Therefore, one organism will have radically different protein expression in different parts of its body and in different stages of its life cycle. In the realm of laboratory medicine, the ultimate goal for proteomics is to link a unique protein expression with human disease and develop a test to identify the relevant protein pattern.
New developments in biotechnology products will be centered on the treatment of more complex diseases and the growing requirement for patient specificity. This trend is encapsulated in terms such as Predictive or Personalized Medicine. The appropriate technological developments to respond to these challenges must be based on global studies of biological systems. With the advent of sequencing of a variety of genomes and initial developments in proteomics we are beginning to have the tools necessary for such global studies. This lecture will concentrate on recent developments in proteomics as an example of such studies. As a definition, proteomics refers to the global characterization of the full set of proteins present in a biological sample. Also higher-order information may be required, such as localization and protein-protein interactions.
Improved high efficiency and selectivity separations will have a major contribution to the characterization of the proteome. While many of the advances in proteomics will be based on the sequencing of the human genome, de novo characterization of protein microheterogeneity will be required in disease studies. Mass spectrometry will be the preferred detector in these applications because of the unparalleled information content provided by one or more dimensions of mass measurement. As has been discovered with the combination of MALDI-TOF and 2D gel proteomics studies, the measurement of low abundance proteins is compromised by the inability to achieve good ionization of complex peptide and protein mixtures. Therefore, highly efficient separation processes are an absolute requirement for advanced proteomic studies.
Peptide mapping with multidimensional HPLC-ion trap mass spectrometry (MS/MS) procedures can allow the characterization of at least 200 proteins per hour. Another advantage of such an approach is the ability to define post-translational modifications such as glycosylation, phosphorylation and sulfation as well as the incorporation of lipid components.
Future developments in the field of proteomics will require the development of a new set of high-throughput tools for the fractionation of biological samples that allow the preparation of protein fractions suitable for the MS/MS approach. This step will allow the characterization of the complex sets of protein mixtures present in different cellular regions. This presentation will show how proteomic approaches can be of relevance to the production of new protein pharmaceuticals as demonstrated by the characterization of novel glycoproteins and other complex biological samples.
Career opportunities in proteiomics
To become involved in this area, you would first need to have a BS in biology with a strong concentration in molecular biology and organic chem and biochem. You could not begin to do research or study proteins until you had a totally solid grasp of the basic functions of cells and genes.
That means that you could go to any school that has a strong program in molecular biology. There are many schools that would qualify... just about any of the large flagship state universities such as Michigan or Wisconsin or SUNY or UC Berkeley. And any of the elite private schools, particularly UChicago, Duke, Harvard, MIT or Stanford. Then you would look for a grad program where there were researchers actively working in this area and apply to do your PhD with them.
If you have a very sound understanding of chem, bio and probably physics and stats as well, then you can go to work in this area
-it is certainly not going to go stale for many years to come.
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