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The whole picture

April 9, 2009

Feature

Uncategorised

In Depth

Proteomics – where has it come from and where is it going? Dr Glen Kemp gives us a glimpse into the future of proteome research.

'PROTEOMICS' as a term was only coined around 14 years ago, making it a relatively new science. It was developed to address a key limitation in classical protein biochemistry. In the traditional approach a single protein or a small number of proteins are separated out from all other proteins in the cell or organism and studied in great detail. Although this approach remains very valuable it misses out some important information. Proteins do not exist in isolation from each other, so although studying pure proteins removes interference from other proteins it also reduces a lot of the complexity and interaction which is actually a key part of how proteins work.

Proteomics aims to redress this by embracing the complexity of a large number of different proteins in the same sample. Just as the human genome project allowed the genetic 'plan' of human beings to be deciphered, so proteomics, one day, aims to provide a means to map out all the proteins in any given cell or organism, at a given time. Once you can do this it enables you to truly understand how the chemical building blocks of life truly interact.

In a way the genome is rather like a dictionary which contains a list of all the possible words in a language. The proteome is more like the individual books in that language – they do not contain all the words, only those needed to tell the story. The way in which those words interact dictates how the story is shaped but unlike a book the proteome is not fixed in time, it is constantly changing as it ages and even in response to changes from outside and within.

For example if you could compare the proteins in a fit healthy cell from those in a diseased cell, you will see some small but vital differences. These different proteins may just be a symptom of the disease, in which case they could help diagnose the disease much earlier, and thus improve the prognosis for the patient. Alternatively, the different proteins may be the cause of the disease, in which case they could act as targets against which new drugs can be developed.

Since different cell types can be characterised by their own unique proteome

"Much was promised from the earliest days of proteomics, and it has to be said, the results so far have not lived up to expectations"

fingerprint, proteomics can be used to study how embryonic stem cells can develop into any one of many different cell types. It can also look at the changes that occur in cells as they age to give us important insights in the aging process as a whole. So there are scientific questions proteomics can help us answer, literally from cradle to grave.

What is more, since proteomics can be applied to any living organisms, it is increasingly being used in agricultural biotechnology to help develop better food crops and more efficient biofuels and in microbiology to both fight microbes and to harness their amazing diversity.

Of course much of this was promised from the earliest days of proteomics, and it

Battle of the 'omes.

• Genome
– This is largely static over time
– Non site-specific
– The Human genome was mapped in 2001

• There are around 22,000 genes
– PCR can be used to amplify DNA

• Proteome
– Dynamic over time
– Site-specific
– Human proteome has not been mapped

• There are around 400,000 proteins
– No equivalent of PCR for proteins

has to be said, the results so far have not lived up to expectations. This is in part because the technology has had to catch up with the theory. Some of the equipment used for proteomics, such as high resolution mass spectrometers, have improved greatly over the last decade, and now allow researchers to discover more proteins, more accurately and more quickly than ever before.

The amount of computing power required to handle the immensely large and complex data generated by this research has also increased exponentially over the decade. And finally, but perhaps most importantly, the people working in the field have had to develop and perfect new techniques and methods to allow them to generate and interpret robust reliable data.

In many ways proteomics has finally caught up with itself, that is not to say there are no more challenges to overcome, but we are now in a better position than ever before to finally reap the rewards of this young and exciting field of science.