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Yeast: From the bakery to the bench

by Anissa Anderson Orr

The nuclei of these blue-stained yeast shine brightly. Image courtesy of James Huang, PhD, Baylor College of Medicine.

Since they are sold in little packs in your local grocery store, and often stashed in the back of the pantry for years, it is easy to forget that yeast is not only a baking ingredient, but also a living organism.

This staple of breads and baked goods makes an ideal model organism for researchers because it is eukaryotic just like humans, meaning it has a nucleus containing chromosomes. Yeast cells also divide in a manner similar to human cells.

“Yeast is an extremely good model because the decisions yeast makes in regard to cell division and the response to DNA damage are very similar to how human cells make decisions,” said Sharon Plon, MD, PhD, associate professor of pediatrics and molecular and human genetics. “And working with yeast is simpler than human cells. It grows more rapidly, and is much easier to grow.”

What is yeast?

Budding yeast growing on a plate

Yeasts are a one-cell, or unicellular, type of fungi. They multiply as single cells that divide by budding, as with budding yeast (Saccharomyces cerevisiae) or direct division, as with fission yeast (Schizosaccharomyces pombe).

S. cerevisiae is commonly used as baker's yeast and for some types of fermentation. Both yeasts have long been used to ferment the sugars of rice, wheat, barley, and corn to produce alcoholic beverages and in the baking industry to expand, or raise, dough.

Research scientists have used yeast as a model organism for decades, because it is easy and cheap to replicate. The average cell cycle for yeast is just 90 minutes. In comparison, the average cell cycle for human cells is about 24 hours.

Yeast rises in importance

The sequencing of the S. cerevisiae yeast genome in 1996 solidified its importance to the scientific world, and revealed its genetic similarity to humans. The yeast genome is just over 12 million base pairs in length and contains about 6,000 genes. About 20 percent of human disease genes have counterparts in yeast.

“The genomics of yeast have allowed us to conduct research on a different scale,” said James Huang, MD, assistant professor of pediatrics. “It is ideal for use in making comparisons with the genomes of more complex organisms.”

In 2001, the Nobel Prize in physiology or medicine was awarded to Lee Hartwell, PhD, of the Fred Hutchinson Cancer Research Center in Seattle and Paul Nurse, PhD, of the Imperial Cancer Research Fund London, United Kingdom for their pioneering work in yeast genetics. Their insights provided the foundation for understanding how normal cells divide. Research scientists today credit these scientists for expanding their knowledge of the mechanisms leading to the uncontrolled growth of cancer cells.

“There has been a longstanding tie between yeast genetics and cancer research, because of the many similarities in how the cell reacts to DNA damage,” Plon said.

Similarities yield clues to human disease

Plon is director of the Baylor Cancer Genetics and Neurofibromatosis clinics. Her lab is using yeast to study how human checkpoint genes work in normal cells and their role in growing tumors. Mutations in checkpoint genes have been found in a large percentage of human tumors and in people who are predisposed to certain cancers.

“Our lab has two goals: to understand why some patients have a genetic susceptibility to developing cancer and to better understand the mechanism behind checkpoint genes to improve therapy, either making cancer cells more sensitive to cancer treatment or to protect normal cells during treatment.”

Yeast research plays a central role in helping her lab meet these goals, Plon said. For example, a gene that has a similar version in yeast causes a rare cancer genetic syndrome called Rothmund-Thomson Syndrome.

Huang is studying yeast to understand the regulation of the cell cycle in relation to cancer and blood disorders. He is currently using yeast to study a rare blood disorder called Schwachman-Diamond syndrome.

The gene was cloned in humans last year, but its function is unclear. All eukaryotes also carry the gene, which suggests that it has a function important enough to be conserved throughout evolution

“Given all the advantages of yeast, we thought we could get some answers about what the gene does more quickly by studying it in yeast,” Huang said.

Other researchers at BCM using yeast as a model organism include Shelly Sazer, PhD, associate professor of biochemistry and molecular and cellular biology who is investigating several aspects of eukaryotic cell cycle progression in S. pombe; Vicki Lundblad, PhD, professor of molecular and human genetics and biochemistry and molecular biology, who is studying telomere biology in yeast; and Eric Chang, PhD, an assistant professor of molecular and cellular biology and a researcher at the Breast Care Center, who is using S. pombe to study the relationship between Ras proteins and tumorigenesis.

“The yeast community is a wonderful, extremely collegial community of investigators that encourage sharing between labs,” Plon said. “As a model organism, yeast is a wonderful opportunity for tudents starting out in research. It gives them a lot of independence in thinking about experiments and how to plan them.”

Other sources of information about yeast can be found at http://www.yeastgenome.org/

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