Researchers First To Catalogue Interactions Of An Organism's Proteins

Now, a team of scientists at North Carolina State University has played a key role in the first analysis of the function of all of an organism's important proteins, the main building blocks of all living organisms. That peer-reviewed research, headed by a team of scientists from Yale University, is described in the July 27 edition of the journal Science.

Proteins are the complex molecules created to carry out the instructions in an organism's genes, encoded in DNA, for how that organism grows and functions. Research on how those proteins work, called "proteomics," is an emerging field of scientific study.

The Yale-NC State proteomics project analyzed how 5,800 proteins in yeast interact with each other, with DNA and with lipids, the molecules that make up the membranes surrounding cells.

"This project is very exciting because up to now we haven't been able to look at how the proteins interact for an entire organism," said Dr. Ralph A. Dean, NC State professor of plant pathology. "We're now able to tell what the important proteins of an organism do."

Dean directs the Fungal Genomics Laboratory at NC State, which helped create the process that makes it possible to quickly analyze an organism's "proteome," or roster of proteins. That procedure separates individual yeast proteins and prepares each for analysis on matchbook-sized "proteome chips." Fungal Genomics Lab scientists also organized the vast amount of data that went into analyzing 93.5 percent of yeast's 6,200 proteins, and assisted in the data analysis.

Dean said this new "high-throughput" procedure, which took only six months to develop for the yeast proteome, could be used to prepare 40,000 important human proteins for analysis. Additionally, it could quickly determine how chemicals, such as pharmaceuticals, interact with human proteins. "It's probably the most powerful tool developed for the pharmaceutical industry to screen drugs," he said.

The researchers chose to analyze the proteins of yeast because yeast's genome was sequenced in 1996, and because yeast is the simplest form of life most closely related to humans. Yeast is a eukaryote, or single-celled organism with a well-defined nucleus.

"Much of the machinery that's in yeast is inside us, in terms of the basic biology that makes the cell work," Dean explained.

During their research, the scientists at Yale and NC State discovered a variety of previously unknown protein interactions that will require further examination. Among these is the interaction between proteins and certain genes, which could allow scientists to better understand the function of those genes. During this project, for example, the researchers were able to describe for the first time the biochemical activities of 69 yeast genes for which they did not know the function.

Scientists will use the results as a launching point for research on the function of proteins of more complex organisms, from plants to humans. The NC State Fungal Genomics Lab will attempt to extend the research to fungi that cause disease in crops and animals.