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| fug. 1 - Crystal structure of the Anthrax Protein |
Proteomics, the study of proteins, is an extension
of genomics. It recognises the significant role proteins play in all cellular
activities.
Most
metabolic activities are regulated by proteins (see fig.1), in the form of
either enzymes, neurotransmitters, antibodies or control elements in cellular
reproduction and gene expression. Founders of the Human Genome Project realised
the importance of proteins and their relationship to the genes that code for
them.
The
Project therefore set out to map all the genes in the human genome, deduce the
DNA sequence of each gene and to identify disease-causing genes, in an attempt
to gain knowledge about cellular functions, possible causes of disease and to
use this knowledge to identify possible drug targets .The Human Genome Project
was effectively completed in 2000.
The Need for Proteomics
Knowledge
of the human genome alone, however, cannot tell us everything we need to know
about cellular activities. This is because although proteins are expressed by
genes through the processes of transcription and translation, there are far
more intracellular proteins throughout the life of an organism than there are
genes coding for them.
One
reason for the fact that there is a greater number of proteins than genes is
the ability of proteins to undergo 'post translational modifications' after
they have been expressed. Post translational modifications (PTMs) occur when
proteins undergo various modifications after or during the translation stage of
protein synthesis. It has therefore become necessary to develop 'Proteomics', a
new discipline that studies the expression, function, identification,
interaction and structure of proteins.
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| Fig.2 - Proteins in a 1D Gel Electrophoresis |
Proteomics and the Study of Disease
Proteomics
has become a useful tool in the study of disease. When proteins are isolated on
electrophoresis
gels (see fig. 2), those involved in a particular disease are often either over
or under-expressed. These proteins are known as 'biomarkers'. Once these
biomarkers have been identified, they can be targeted with drugs or used as
drugs themselves if they are found to be absent in diseased tissue.
In
sufferers of prostate cancer, for instance, the protein biomarker PSA is over
expressed. This information can therefore prove useful in diagnosing sufferers
of this disease. Another example can be seen in the recent discovery of a
protein that occurs in people who suffer toxic reactions to chemotherapy drugs.
Because it has been identified, the development of a drug targeting this
protein is now possible.
A
non-invasive screening method for breast cancer is now also feasible because of
the discovery, through proteomic techniques, of a protein in human tears
(lacryglobin).This protein is identical to one that is over expressed in breast
cancer.
Other Applications of Proteomics
Another
application of proteomics is in the identification of biomarkers in heat
tolerant varieties of wheat. When subjected to heat stress a certain wheat
variety called 'Fang' expresses proteins that are thought to be responsible for
its heat resistant qualities. The identification of these proteins and the
genes responsible for them provides breeders with the information needed to
cultivate wheat varieties with this desirable characteristic.
Proteomics
also provides scientists with information about protein-protein interactions.
Knowledge of these interactions is of great relevance because they are often
the basis of complex chemical signaling pathways in cells. In addition,the
location of a particular protein within a cell can be determined using
proteomic techniques. This is important because it often indicates the type of
metabolic processes the protein is involved in.
Proteomics in Industry
Numerous
proteomics companies have emerged in the last decade as a response to the need
to identify and characterise proteins associated with disease or other
metabolic manifestations of interest. Matritech, for instance, uses proteomic
techniques to develop diagnostic tests for breast, bladder, cervical and prostate
cancers. Its NMP22 bladder cancer test is FDA (Food and Drug Administration)
approved and is currently being used by urologists.
Companies
such as MDS Proteomics operate in conjunction with pharmaceutical organisations
to discover drug targets that can be treated with small molecules or
antibodies. Although still in the pre-clinical trial stage for many of their
products, these organisations are providing the technology needed to achieve
effective therapeutic solutions in the near future. Some of this technology
includes electrophoresis and mass spectrometry systems, coupled with advanced
computing and drug screening techniques.
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| Fig. 3 - PTM Showing Phosphorylation |
The
applications of proteomics are extensive: not such a surprising revelation when
the significance of proteins in cellular metabolism is considered. Moreover,
proteomics offers a more efficient pathway towards drug discovery than
genomics, as it studies the proteins responsible for disease rather than the
genes that code for them. Continued expansion of this rapidly growing area of
biotechnology is therefore to be expected.
References
Graves,P.
and Haystead,T., 2002, 'Molecular Biologist's Guide to Proteomics',
mmbr.asm.org, accessed 12/5/2010
Fuji-Keizai,
2003, 'Post Genome Project Era Proteomics R&D Competition', fuji-kezai.com,
accessed 10/5/2010
Protein
Science.com, 2007, 'Companies', proteinscience.com, accessed 13/5/2010
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