Yale University researcher Michael Snyder and his colleagues have created the first microchip able to analyze virtually all yeast proteins, the chemicals that carry out the activities necessary for life.
The new protein chip holds promise for significant advances in the study of the function of proteins in other organisms beside yeast, including humans. "Most development occurs through the interactions among proteins," said Snyder, professor and chair of the Yale Department of Molecular, Cellular and Developmental Biology. "Diseases can arise when proteins do not interact properly. This technology allows us to get at the function of many of the different proteins far faster than current methods. This is opening up whole new areas that have never been approached before."
Besides increasing knowledge about how proteins function, the new protein chips could speed the development of new diagnostic methods, advancements in drug discovery, and improvements in therapies for diseases.
Announcement of the development of the new protein chip came in the July 26 online version of the journal Science and appeared in an article published in the September 14 issue.
Development of the new protein chip was based on previous knowledge of the identity of all 6,200 genes in a yeast cell. Each gene encodes for a protein, which interacts with other proteins to develop and sustain cell life. Prior to the Yale scientists' discovery, studying proteins on a large, nearly complete scale had never been done, and many scientists believed it was not possible.
Snyder, who is also co-director of the recently announced Yale Center of Excellence in Biomedical Computing, directed the study, which involved the collaboration of Heng Zhu, a post-doctoral fellow in his laboratory, and other Yale colleagues, along with investigators from North Carolina State University. They cloned and purified 5,800 different yeast proteins, representing 80 percent of the entire proteome, or complete protein make-up, of yeast. They then utilized robotic technology for systematically spotting the proteins within a postage stamp-size space on a nickel-coated, glass microscope slide, a so-called microarray chip. The chip is capable of holding more than double that number, which allows the researchers to duplicate the pattern of the proteins to check for accuracy in experiments.
Utilizing laser scanning equipment and computer analysis programs already commonly used in the study of gene microarray chips, the scientists looked at the interaction of the proteins with other proteins that had been tagged with fluorescent colors that glow when one protein binds with another. The initial study identified many previously unknown protein functions.
Snyder has begun work to apply the same technology to create a human protein chip. He said that humans very likely have proteins that number in the hundreds of thousands or more. By focusing on one protein produced by each of the few thousand genes that are already known, Snyder believes such a chip may lead to rapid advances in the understanding of human biology. "It is a very large, challenging effort that requires the collaboration of many scientists," he said.
Yale University has licensed the technology behind the protein chip to a recently established New Haven-area biotechnology company, Protometrix, Inc., which will seek to use the chips for commercial purpose. The possible uses include study of protein functions in virtually all living organisms. Snyder, who is a scientific advisor to the new company, said, "We anticipate that the technology will become widespread within the academic community and will prove to be a valuable tool for the pharmaceutical and other industries."
Journal
Science