Research & Discovery

In Beer Yeast, UVA Scientists Find Potential Path to Starving Cancer

New cancer treatments could be on the way, thanks to a surprising discovery involving yeast used to brew beer.

University of Virginia School of Medicine scientists and collaborators at the European Molecular Biology Laboratory in Germany discovered a never-before-seen adaptation that allows yeast cells to go dormant when nutrients are scarce. This ability to hibernate during stress mirrors cancer’s ability to survive nutrient shortages that accompany the cancer cells’ unchecked growth.

The unexpected findings could lead to new strategies for making cancer cells more vulnerable to starvation and easier to treat, said researcher Ahmad Jomaa of the School of Medicine’s Department of Molecular Physiology and Biological Physics.

“Cells can take a break when things get tough by going into deep sleep in order to stay alive, then at a later point, they seemingly just come back,” said Jomaa, part of UVA’s Center for Membrane and Cell Physiology. “That’s why we need to understand the basics of adaptation to starvation and how these cells become dormant to stay alive and avoid death.”

Surviving Stress

S. pombe is a type of yeast used for centuries to brew beer. It’s also an invaluable research tool for scientists because of its similarity to human cells. By better understanding S. pombe, researchers can better understand fundamental cellular processes in healthy and cancerous cells.

Ahmad Jomaa of the School of Medicine’s Department of Molecular Physiology and Biological Physics says studying the yeast cells gives clues how cells “can take a break when things get tough by going into deep sleep in order to stay alive, then at a later point, they seemingly just come back.” (Contributed photo)

Working with Simone Mattei and colleagues at the European lab, Jomaa and his team, with support from the Searle Scholars Program, the American Cancer Society and UVA’s Department of Molecular Physiology and Biological Physics, discovered that when the yeast cells’ batteries hibernate to avoid stress, they wrap themselves in an unexpected blanket. The surfaces of these batteries, called mitochondria, become coated with deactivated ribosomes, cellular machinery that normally make proteins.

It remains a mystery why these inactive ribosomes attach themselves to the mitochondria. “There could be different explanations,” Mattei said. “A starved cell will eventually start digesting itself, so the ribosomes might be coating the mitochondria to protect them. They might also attach to trigger a signaling cascade inside the mitochondria.”

Free Tuition for Virginia Households making <$100K, Learn More

Researchers were able to visualize how the ribosomes attach to the mitochondria down to the molecular level using powerful single-particle cryo-electron microscopy and cryo-electron tomography. They were surprised to discover the ribosomes had attached themselves “upside down,” using a small subunit of their anatomy. This type of interaction had never been seen before and could help decipher the secret of how cells enter and wake up from hibernation.

S. pombe, pictured in an electron microscope image, is a type of yeast used for centuries to brew beer. It’s also an invaluable research tool for scientists because of its similarity to human cells. (Photo by Michael Purdy)

“We knew that cells would try to save energy and shut down their ribosomes, but we were not expecting them to attach in an upside state on the mitochondria,” said Maciej Gluc, a graduate student in Jomaa’s lab and co-first author of a new scientific paper describing the discovery.

Cancer cells face perpetual nutrient shortages because of their unchecked growth, and they often slip into dormancy to survive and escape detection by the immune system. Understanding how they do this could lead to new ways to target those cells, improve patient outcomes and prevent relapses.

During stress, mitochondria in the yeast cells become coated with deactivated ribosomes, cellular machinery that normally make proteins, but they attach in an unusual “upside-down” manner. (Illustration by Isabel Romero)

“For the next steps, we aim to understand not only how cells regulate entry into dormancy, but also how they awaken from this deep sleep. For now, we will use yeast because it is much easier to manipulate. We are now also investigating this in cultured cancer cells, which is not an easy task,” Jomaa said.

“Ultimately, I hope that my group’s research will lay the foundation for discovering new markers to track dormant cancer cells. These cells are not easily detected in diagnostic settings, but we are hopeful that our research will generate more interest in helping us reach our goal.”