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In the early 1990s, Tom Stevens found himself on a tangent—a tangent that led to one of the most exciting discoveries of his career. Roughly ten years after establishing a chemistry lab at the UO associated with the Institute of Molecular Biology, Stevens’ research on protein targeting took an interesting turn. The lab had been focusing on the mechanism by which proteins within a cell are directed to their appropriate destinations. But while working on a particular yeast protein involved with targeting, the researchers noticed that a protein sequence had removed itself from the protein construct and that the neighboring protein sequences had reconnected. This “splicing” process usually occurs at the RNA level. Stevens says, “We now see it throughout the microbial world but it doesn’t appear very often in the eukaryotic world.” The lab had stumbled upon the first discovery of protein splicing, which they continued to work on for the next five years, from 1990 to 1995.
During this time, researchers from Stevens’ lab also continued their work on understanding protein targeting, sometimes called protein sorting. Stevens compares this mechanism to a railway system: “The sorting process begins in a compartment called the endoplasmic reticulum. From the ER, proteins are translocated to a number of different destinations. [The ER] is similar to a train station… some things never leave, some things leave and go to the next compartment, some things go to the next compartment and keep going.” Each protein has its own targeting signals; Stevens and his fellow researchers have spent years working to understand these signals and how they are recognized by the “machines” that stamp the protein’s ticket and figure out which train the protein is supposed to take.
Like scientists around the world, Stevens uses yeast as a model system. “It’s one of the premiere simple, straightforward eukaryotic cell model systems,” Stevens says. “Invariably we find that the same network of proteins that works in a particular way in yeast, works the same way … in humans to do very similar functions. So the economy of information that one gets by studying these simple model systems is immense.”
Stevens describes his field as an “interface between chemistry, biochemistry and molecular genetics, understanding how nature [and cells] work … at the biochemical, mechanistic level.” He works to apply the quantitative aspects of science to the biological sciences, to better understand the chemistry of life.
—SB
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