Proteomics Takes a Leap

Seeing spots. A nickel-coated microscope slide dotted with 6566 protein samples representing 5800 unique proteins.

In this era of high-speed biology, studying proteins can be maddeningly slow: Their complex chemistry and delicate 3D shapes make them hard to analyze. But a breakthrough may speed things up dramatically. In a paper published online today by Science, researchers report creating a protein chip that can analyze 5800 yeast proteins all at once. Such chips could aid research--and clinical diagnostics--by quickly revealing the partners with which thousands of proteins interact.

The new protein chip is a close cousin to DNA chips, postage-stamp-sized surfaces dotted with nucleic acid sequences that can track the activity of thousands of genes in a tissue at once. Although DNA chip technology is commercialized and now widely used in research labs, scientists have struggled for years to make similar chips to analyze the full proteome, the collection of all proteins in a tissue or even an organism. But most chips so far can only analyze a handful of different proteins

That record has now been shattered by Yale University biochemist Michael Snyder and his colleagues at Yale and North Carolina State University in Raleigh. To do so, they first cloned 5800 yeast genes, inserted the genes into other yeast cells, and coaxed the bugs to overexpress the proteins, which they laboriously purified and collected. They then used a now-standard DNA array robot to dab rows of tiny samples of each yeast protein atop a glass microscope slide. To find out what the yeast proteins bind to, they spritzed the slide with a solution of test proteins. Adding a fluorescent label then highlights the spots where the test proteins bound.

Using several versions of this technique, Snyder and his colleagues were able to rapidly identify the proteins that interact with the thousands of arrayed yeast proteins. And in so doing they managed to discover 33 new proteins that bind calmodulin--a widespread protein involved in calcium sensing--and 52 proteins that bind phosphotidylinositides, cell membrane proteins involved in growth, differentiation, and cytoskeletal rearrangements.

"This is a biochemist's dream, to be able to look for any activity over the entire proteome," says Eric Phizicky, a biochemist at the University of Rochester Medical Center in New York. In hopes of fulfilling more dreams, Snyder has launched a New Haven, Connecticut-based company called Protometrix to make protein chips. He will have plenty of competition. Over a dozen companies are currently racing to commercialize protein chips, laying claim to an emerging market that is estimated to grow to $500 million annually by 2006.

Related site

Michael Snyder's Laboratory Web Site

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