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Caprion s John Bergeron Seeks Payoff in Subcellular Compartments



Name: John M. Bergeron

Position: Chief Scientific Officer, Caprion Pharmaceuticals, Montreal, Quebec

Age: 55

Prior Experience: Chairman of the Department of Anatomy and Cell Biology, McGill University

In a typical proteomics discovery experiment, the general protocol might go something like this: take extracts from diseased and healthy tissue or body fluids, lyse the cells, separate the proteins, and identify the proteins that differ in expression level using mass spectrometry.

So besides the details, what’s missing?

John Bergeron, chief scientific officer of Caprion Pharmaceuticals, would say the experiment lacks a way to determine where those proteins originated in the cell. His Montreal-based company has staked its reputation on the belief that separating a cell into its distinct compartments, or organelles, such as Golgi bodies, phagosomes, and peroxiosomes, before analyzing the proteins will allow his scientists to identify more proteins, and more quickly identify each protein’s cellular function.

Bergeron puts it this way: “If you took any one of our organelles, say the plasma membrane, and put it on a 2D gel you’d have few hundred spots. If you now matched those spots from the purified organelle to those of the total cell lysate, you’d find that 90 percent of the spots in the organelle don’t hit anything in the total cell lysate. The reason is that the dynamic range of protein [concentration] on the 2D gel from the cell lysate is far below that of the proteins as they exist in the cell.

“Consequently, the organelle concentration method provides a tremendous concentration of low abundance proteins. In addition, in each of these organelles we find a large number of unassigned or novel proteins, and since we know the functions of most of the organelles in the cell it gives us great insight into what [the protein’s] function might be.”

Although Bergeron didn’t found Caprion, a 1998 spin-off from a company called Advanced BioConcepts, his credentials as a cell biologist are solid. He studied under 1974 Nobel laureate George Palade, and currently serves as chairman of the Department of Anatomy and Cell Biology at McGill University in Montreal.

As a result, Caprion’s approach to proteomics, a suite of technologies known as CellCarta, includes a number of traditional cell biology techniques specific to subcellular research. To isolate the individual organelles, and maintain the structure and orientation of membrane-bound proteins that make up the boundaries of those organelles, Bergeron and his team treat their samples with classical density gradients, centrifugation, and magnetic and silicon beads. Caprion researchers also use electron microscopy to study the number of contaminants found in specific samples as a method of quality control.

Bergeron’s approach to separating the proteins found in each compartment involves the use of 1D and 2D gels, as well as liquid chromatography-based separation techniques. However, the group uses 2D gels merely “as a complementary tool as opposed to an analytical tool” because 1D gels provide the maximum sampling of the proteins in an experiment, he said.

To identify the novel proteins that Bergeron claims CellCarta produces in such quantities, his team at Caprion has assembled a squadron of 9, and soon to be 16 mass spectrometers that run 24 hours a day, seven days a week analyzing proteins. “Tandem mass spectrometry is our workhorse” but the company also uses triple quadrupole, ion trap, and MALDI mass spectrometers he said. Caprion has an early-access agreement with Micromass, but is not restricted to buying instruments from one vendor, Bergeron added.

The company also has alliances with Sun Microsystems, Oracle, and CGI to develop databases and protein interaction maps to archive and validate the experimental results. In fact, Caprion is in the process of submitting a patent on a method for quantitatively measuring the relative abundances of tryptic peptides using “an inherent property of the mass to charge ratio of each tryptic peptide,” Bergeron said.

As for the pharmaceutical part of Caprion’s full name, the company currently has relationships with Idexx Laboratories and Johnson & Johnson to develop antibody diagnostics for the prion protein, but Bergeron is reluctant to say how deeply the company plans to involve itself in developing small molecule compounds. “We’re just overwhelmed by this unexpected aspect of having so many novel proteins fall into our lap,” Bergeron said. “Just trying to make sense of all this, with the size that we are, is keeping us fully occupied right now.” —JSM

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