Stan Fields uses the yeast genome to study the functions of proteins

Stan Fields

The yeast may be the same, but you won't find the research Dr. Stanley Fields conducts on these single-celled organisms happening in any of our fine local breweries.

Yeast cells are relatively simple. They contain chromosomes in a nucleus and a typical cell membrane, which makes them a good target for investigators who want to study interactions between molecules inside the cell.

But yeast cells are fungi. So, aside from a loaf of bread or occasional trips to the local pub, what do they have to do with us?

"The fundamental processes in a yeast cell and a human cell are evolutionarily conserved," explains Fields, a professor of genetics and medicine and an investigator for the Howard Hughes Medical Institute.

This means the genetic material in yeast and the essential functions of its proteins have been around for a long, long time, perhaps close to one billion years. Now, with its 6,000 genes compared to our 80,000 to 100,000, yeast wasn't quite the same speed demon on the evolutionary scale, but at some point we did share a common biological ancestor.

Thus, yeast genes and sequences bear a resemblance to our own. The similarity allows researchers who use a broad range of techniques to study the functions of yeast proteins to eventually apply that knowledge to humans, Fields said.

"Our approaches to yeast should be applicable to humans in a few years," he said.

Fields will give a Science in Medicine lecture on his research, titled "Genomic Approaches to Protein Function: Yeast and Beyond," from noon to 1 p.m on Friday, March 20, in room T-625 of the Health Sciences Center.

A major advance that set the stage for the future of this field of research was the sequencing of all of the yeast's 6,000 genes, completed by a worldwide collaboration of laboratories in 1996. Fields and the investigators in his lab are taking that work to the next level by trying to understand some of the functions of the proteins produced by these genes.

"So far, approximately half of the proteins have been assigned functions," Field said. Those functions include important roles in DNA repair, DNA replication and the cell's ability to metabolize glucose.

Each protein in our body serves a specific purpose, whether as an enzyme, hormone or a lipoprotein. That purpose, or function, is determined by the molecular structure of the protein, which in turn is derived from the structure of the gene that encodes it.

But putting a finger on a protein's function is no easy task, nor do researchers find out the exact roles at once. Fields may in fact be best known for developing the most common technique used for taking one of the first steps toward functional analysis. Called the two-hybrid system, the technique allows researchers to determine whether two proteins will interact.

The interactions between proteins allow researchers to gain important clues about their functions. Finding an interaction of a novel protein with a protein that exists in the nucleus may tell us something different about function than finding an interaction with a proteinin the cell membrane, Fields said.

When all of the interactions between the proteins are identified, a "protein linkage map" will have been developed that will help usher in major advancements in understanding the functions of the same proteins in humans.

"But it's early days for this research," Fields says. "It's a continuing process."

In other words, it will evolve.

Fields earned a Ph.D. in molecular biology from the Medical Research Council Laboratory of Molecular Biology and Cambridge University in England in 1981. He has been a professor of medicine and genetics at the UW School of Medicine since 1995; in 1997, he became an investigator for the Howard Hughes Medical Institute. ¶

Will Morton