Disease research kneads yeast

Kate Thackrey

The humble baker’s yeast, Saccharomyces cerevisiae, is one of the best-studied organisms on the planet. By 1996, scientists had sequenced the entire yeast genome and have been using it as a model for similar types of cells for decades.

While the similarities between humans and yeast might not be immediately apparent, we share nearly 4,000 genes due to a common ancestor from around a billion years ago.

Researchers Aashiq Kachroo and Jon Laurent from the Marcotte Lab at the University of Texas have spent the past few years using these similarities to their advantage. They replaced 414 genes in yeast cells with their human counterparts in 2015, jumping up to almost 900 genes with their current research on E.coli and plant genes.

One of the biggest impacts of replacing genes in the yeast cells, Kachroo said, is the opportunity it presents in the world of disease research.

“You can imagine hundreds of these genes involved in important processes in humans, these have disease implications,” Kachroo said. “By putting these genes in yeast cells, we can now test if mutations can
cause disease.”

To figure out whether the yeast cells would survive with human genes, the pair chose only genes that the cells needed to survive, such as those that spark development.

“We restricted our tests to those genes that are essential,” Laurent said. “If we put the human gene in and the yeast then grows, then we know the human gene is functioning.”

After testing they found that 47 percent of the yeast cells grew healthily with human genes.

The pair also discovered how to predict which genes would work and which would fail. It turns out that of the 104 different variables that could affect the genes, the most important ones deal with interactions between the proteins made by genes.

“The most predictive properties have to do with the network of proteins that a gene or protein interacts with,” Laurent said. “That suggests that these proteins, rather than losing the ability to replace [other proteins] alone, lose the ability to replace as a module of similar proteins.”

Over the past year, Kachroo and Laurent have also been working to meld yeast with the bacteria E.coli, along with some types of plants.

“Nearly every organism has some common feature with every other organism.”  Kachroo said. “It’s surprising that the bacterial genes which diverged nearly two billion years ago function the same way.”

The team also found preliminary data that supports their first paper’s findings, with a success rate of roughly 50 percent in transplanting E.coli genes into yeast cells. Kachroo said the new report will be published soon.

“This speaks to the universality of these core genes, which are able to swap despite the context being different in the cell.” Laurent said.

Yeast cells can also divide every 90 minutes, as opposed to the days it takes some human cells, meaning researchers can carry out their experiments faster.

“Yeast has been used in science for a long, long time,” Kachroo said. “It’s incredibly fast and efficient. You can do not only one mutation but billions of mutations.”

By using yeast cells, researchers would no longer have to jump through the ethical hoops of gaining human samples.

“We don’t have to work in human cells anymore, we don’t have to go to patients.” Kachroo said. “It’s a completely isolated system.”

Eventually, Kachroo said he hopes to use the method to predict how mutations will affect human cells, in order to prevent diseases from occurring.