A series of experiments in the 1990s that tested how humble yeast cells remove waste and toxic material could have started the journey that results in major breakthroughs in how cancer and neurodegenerative diseases like Alzheimer’s are treated.
Japanese biologist Yoshinori Ohsumi is the scientist who conducted those experiments, and his work earned him the 2016 Nobel Prize for Physiology or Medicine. Ohsumi’s research and its potential ramifications were the subject of the “Nobel at Noon” lunch and learn presentation by Christopher Phiel, PhD.
Phiel is a member of CU Denver’s Department of Integrative Biology. He explained how Ohsumi won the award for his groundbreaking research on how cells recycle worn out parts. The same process keeps cells healthy by removing potentially toxic proteins and waste, and its failure is a characteristic of neurodegenerative diseases and cancer. Ohsumi’s basic scientific research could lead to real-world therapies and medical treatment.
Taking out the trash
Ohsumi studies a process called autophagy. It is a fundamental part of how cells work, from single-cell molecules like yeast to human cells. The word literally means “self-eating” in Greek.
Or, as Phiel explained it to an audience of non-specialists, autophagy is the way organisms “get rid of the garbage” that builds up in cells. In more scientific terms, Phiel said it’s about how cells destroy proteins, a subject important enough that the Nobel Prize has gone to scientists working on the subject three different times.
Ohsumi has said in profiles that when he began his work in the 1980s he was looking for an area that was overlooked by other researchers. His motivation for taking up the subject wasn’t to blaze a trail that would lead to a Nobel Prize, he has said, but one born of frustration with unsatisfying work early in his career—an admission that might comfort young researchers everywhere.
Ohsumi wouldn’t be overlooked for long, though, for reasons Phiel explained. Ohsumi’s experiments on baker’s yeast identified the genes for autophagy, explained the process and ultimately showed the process was virtually identical in human cells.
“What Ohsumi has done is shine a light on what this process was and define it for us,” Phiel said. “Now we know why it happens.”
Breakthrough beyond basic science
And there’s a lot happening. As Ohsumi and others continued researching, they found that autophagy was a key part in providing energy to cells, helping them respond to stress and starvation, and eliminating bacteria and viruses. It even contributes to the development of embryos.
Nobel at Noon schedule
Oct. 28 – Chemistry
Nov. 4 – Medicine
Nov. 11 – Economics
Nov. 18 – Peace
Dec. 2 – Literature
Dec. 9 – Physics
All presentations are at noon in the Jerry Wartgow Welcome Center in the Student Commons Building, 1201 Larimer St.
The presentations are free and open to the public. Click here to reserve a spot.
But one area of research in particular has caught the attention of scientists and even the media—the apparent relationship between autophagy and diseases. The disruption of autophagy has been linked to neurodegenerative diseases like Alzheimer’s and Parkinson’s, cancer, Type 2 diabetes, and many ailments that come along with aging, according to the Nobel Prize committee.
Phiel explained that in those cases it appears that “the autophagy machinery gets overloaded.”
“There are several examples of neurodegenerative diseases, like Alzheimer’s, Parkinson’s and Huntington’s Disease, where a characteristic of all those diseases is an accumulation of misfolded or toxic protein,” Phiel said.
“It looks like the cell is trying as hard as it can to get rid of it, but there is too much, it can’t keep up, and that causes the cell to die,” he said. “Perhaps re-stimulating autophagy in these cells could be one way to treat not just one but several types of neurodegenerative disease.”
If scientists determine how to do that, it could lead a major breakthrough in how many diseases are treated.
“People have been trying to target those individual toxic proteins, but what if you could target a process that is common to all of them?” Phiel said. “That way you don’t have to be so specific, and it might be a general therapy,” Phiel said. In fact, there are currently FDA-approved drugs that have been shown to stimulate autophagy, and researchers have been investigating their use in animal models. Still, it could be years before scientists understand the exact relationship between autophagy and disease, Phiel said.