Total protein scan approaches reality

 作者:辛匝     |      日期:2019-03-06 12:04:26
By Philip Cohen, San Franciso For the first time, nearly all the proteins from a single organism have been produced, purified and biochemically tested in an area the size of a postage stamp. Experts say such “proteome chips” are going to revolutionise medicine and biology. The US researchers who created the chip have already used it to study the biochemistry of 93 per cent of the proteins of brewer’s yeast Saccharomyces cerevisiae, a total of 5800 molecules. One of the study’s leaders, Michael Snyder of Yale University in New Haven, Connecticut says this type of technology will ultimately shed light on the function of our own cells. “While a lot of work needs to be done, extending this to the set of human proteins is clearly possible,” he says. Human cells contain 30,000 or more genes and may possess many times more protein species. “Doing this with so many proteins is impressive,” says Gavin MacBeath of Harvard University who is also a pioneer of protein chip technology. “I’m green with envy.” The human and other genome projects have given biologists a vast store of information about the DNA of many organisms. The next great race is to identify regions of the DNA called genes, which encode proteins, and to understand each protein’s function. The full set of proteins, or proteome, of a cell performs nearly all of its complex functions. In the yeast genome, genes for about 6200 proteins have been identified. So far Snyder’s team has managed to use genetic engineering tricks to produce 5800 of these proteins, purify them and attach each in a pair of duplicate drops. The final array fills just one half of a glass microscope slide. They then tested the ability of each protein spot to bind to a target. Seven different targets were assayed: a signalling protein called calmodulin and six greasy chemicals called phosphotidylinositides, which are also involved in cellular communication. Each experiment generated a flood of new biochemical data. For instance, six known calmodulin binding proteins were identified – as well as 33 new potential partners. By using their database of information on these proteins, the researchers were able to determine a common structure in many of the proteins that probably attach to calmodulin. In some cases, this was the first biochemical clue about the function of an otherwise mysterious protein. However, the process wasn’t perfect. For instance, four known calmodulin binding proteins were not detected because there were not enough molecules of the protein attached to the chip to generate a signal. “If they make these chips at an industrial scale, there are clearly improvements they would want to make,” says MacBeath. “But for a first demonstration, it’s amazing.” Snyder and his colleagues will soon be launching a company dubbed Protometrix to commercialise their technology. His team is also busy following up on some of the new protein biochemistry they’ve discovered. “That’s the one problem with the technology,