For protein researchers, all roads lead to the proteome
By Robert Levy
Jarrod Marto, PhD, director of the Blais Proteomics Center at Dana-Farber, adjusts a mass spectrometer, which measures the masses of individual molecules that have been electrically charged.
The problem could be a plane crash, a dam break, or a bridge collapse. Investigations of mechanical and structural failures generally follow two lines of inquiry: Did the mishap stem from a flaw in design or a flaw in materials (or both)? When breakdowns occur in the complex mechanical system within human tissue, as invariably happens in cancer, the investigation should be no less thorough.
For all its variety, cancer is essentially a disease of malfunctioning cells. Errors in a cell's genes, which hold the code for making proteins, cause the cell to produce the wrong proteins at the wrong time, or produce defective ones. Proteins normally involved in cell division – carrying signals to various parts of the cell, telling it when to start and stop dividing, and when its lifespan is over – become unfit for their tasks. In the past half-dozen years, new vistas have opened in the "design" side of the cancer question – in the gene blueprints for individual proteins. The mapping of the human genome, the directory of all genes in human cells, invigorated the search for gene abnormalities, or mutations, associated with cancer. Meanwhile, technological advances have made it possible to take a "group picture" of the activity levels of thousands of genes at a time. This enables researchers to compare gene-activity patterns in normal and cancerous cells, and in different types of cancer cells, leading to therapies targeted at specific mutations.
At the same time, and largely in the shadow of the genomics revolution, has come renewed attention to the "materials" aspect of molecular research – the proteins that carry out literally every aspect of cell life. Progress in this area, as in genomics, has been driven largely by technological innovation, in the development of machinery that sifts through the protein contents of cells with extraordinary speed and precision. The study of all the proteins within cells – known as "proteomics" – is also held to have unique promise for understanding the cancer process and attacking it with new therapies.
Recognition of this potential led Dana-Farber in 2004 to establish a proteomics laboratory, creating a base for large-scale protein studies. And it prompted DFCI Trustee Jack Blais and his wife, Shelley, to donate $16.5 million last fall – the largest gift from individuals in the Institute's history – to create the Blais Proteomics Center here. The center, which will take shape over the next five years, aims to make Dana-Farber a world leader in proteomics science and give DFCI scientists access to the latest technology and best expertise in the field.
"Much remains to be learned about the function of normal and cancer cells at the most basic level," says Dana-Farber's Chief Scientific Officer, Barrett Rollins, MD, PhD. "To do that, it's necessary to look at the roles proteins play in the life of cells, and how those roles become disrupted in cancer. Proteomics provides the tools."
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