13 February 2006

Proteomics and Genomics: A Synergistic Pairing

Understanding what is going on inside the living cell is becoming both easier and harder. It is becoming easier because of the tremendous advances achieved in genomics, such as the human genome project. Similarly, knowledge of non-coding RNA and of the dynamic protein environment of the cell is increasing.

I remember a former professor of biochemistry lamenting a number of years ago, how it seemed that everyone he knew had gone to genomics, leaving him virtually alone to study proteins. I doubt that he would say the same thing now. Proteonomics is taking on an ever more pivotal role in the study of cellular function.

What is proteonomics? From this research lab at Aberystwyth University in Wales:

For those who are not familiar with proteomics, it is the investigation of the protein complement of an organism instead of the genetic material which is used in genomics. The genome of an organism is generally static, whereas the proteome is largely controlled by protein expression and can be changed by any number of factors. An organism will have a fixed number of genes (no doubt there are a few exceptions), a certain number of which will be expressed at a given time. Using proteomics we can look at the products of these genes and thus focus on the proteins that are actually present in that organism at the time of sampling. In this way we can investigate the response to different stimuli or compare, for instance, a disease condition to a control. Proteomics has a number of key advantages over other techniques such as microarrays that are also used for this kind of work. Using proteomics we look at the proteins present in the cell, not the mRNA from which it is translated. Thus we are looking at the true picture of what is happening inside an organism and not at what might be happening. Another fundamentally important advantage of proteomics is that it is possible to identify proteins that have been post-translationally modified. The modification of proteins plays a key role in the function of many proteins, therefore, our ability to look at and identify changes in these proteins can be of key importance. Many proteins are activated by phosphorylation, or are expressed in an inactive form (proproteins, preproteins or preproproteins) and must be cleaved before they become active. These modifications will produce changes in the size, the pI or both and can be identified on 2 dimensional gels by the anomalous migration of the protein under investigation.

While genomics startups have been getting venture capital for about thirty years now, proteomics startups are fewer, and may have to scrap a little harder for the money and respect. Here is a description of a recent funding for a proteomics based drug discovery company:

Lectus’s mission is to discover and develop first and best in class next-generation ion channel drugs to treat pain, urinary incontinence and angina. The new funds will be used to advance the company’s existing programs initiated though exploitation of its proprietary proteomics research engine (LEPTICS) and to provide opportunities for commercial partnerships with pharma companies. Lectus was founded with seed funding from the Sulis Seed Corn Fund, which is managed by Quester.

Ion channels are proteins that control the flow of ions, such as sodium, calcium and potassium, into and out of mammalian cells. They are integral to muscle movement, nerve impulse transmission and cardiovascular function. Historically, drugs targeting ion channels have been very successful and still generate well in excess of $6 billion in sales per annum. In recent years however, efforts at identifying novel ion channel therapeutics have focussed on targeting the pore forming domains of ion channels and despite billions of dollars spent in R&D, this approach has not yielded further significant clinical success. This is believed to be mainly because of the side effects associated with the lack of specificity of this approach. Lectus’s next-generation ion channel therapeutics, selectively targeting ion channel accessory proteins, are anticipated to have a significantly enhanced safety profile with resultant therapeutic and economic benefits.

For those interested in the history of proteomics, this interesting blog entry provides some historical background.

Protein receptors are a very hot research topic, since these proteins act as interfaces between biological compartments, controlling the passage of signals from cell to cell, hormones to cell, etc. Other proteins are enzymes, structural proteins, cellular motors, etc. Proteomics opens up another huge continent of study for researchers, providing opportunities for breakthroughs unimaginable at the present.

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