The 2016 Nobel Prize in Physiology or Medicine highlights a process that is integral to aging, cancer, and infectious disease, but has not been well known outside of cell biology.
On 7 December 2016, Professor Yoshinori Ohsumi from the Tokyo Institute of Technology received the Nobel Prize in Physiology or Medicine. Ohsumi was honored for research on autophagy, a ubiquitous cell process that previously received little public attention. Since the Nobel announcement, Ohsumi received a Life Sciences Breakthrough Prize from the technology pioneers and funders of Facebook and Google.
After the Nobel announcement, Ohsumi talked with Adam Smith, chief scientific officer of Nobel Media, about the growth in the field. “When I started my work,” he said, “probably every year, 20 or less papers appeared on autophagy. Now more than 5 000 or something like that. It’s a huge change within probably these 15 years or so.”
What autophagy is and why it matters
Autophagy, from the Greek words for self and eating, is often described using terms like “garbage” and “recycling.” It is, however, a vital service provided by the cell’s vesicular system for the entire organism. Autophagy breaks down organelles such as mitochondria, rescuing their components to construct other cell parts. Autophagy destroys pathogens. It sacrifices nonessential enzymes to supply amino acids for essential proteins.
In praising Ohsumi, basic and applied scientists noted that autophagy touches on human conditions from cancer to cognitive impairment. Understanding this process is critical for understanding aging. Cell biologists said that when Ohsumi began, he certainly never expected that his research would have such diverse implications. For an example of how Ohsumi’s work advances basic and clinical research, see our report in this issue on work by Steven Goldman, including a study about Zika and autophagy.
Earlier Nobel winners inspire a career change
Ohsumi was born in 1945 in Japan and earned a PhD from the University of Tokyo. He did postdoctoral work at Rockefeller University in New York and the University of Tokyo, later moving to the National Institute for Basic Biology, Okazaki, Japan. He is now at the Tokyo Institute of Technology. He began his award-winning work, which is a combination of classic genetics and innovative cell biology, during his postdoctoral period.
Ohsumi works on yeast, a common model organism with strengths in genetic manipulation but weaknesses in microscopy because of its small cell size. Ohsumi used yeast mutants that allowed him to use microscopy to view autophagy. He applied standard yeast genetic methods to identify genes that direct autophagy. He was not always a yeast geneticist, however.
The Nobel Prize is “richly deserved” and “wonderful recognition” for Ohsumi, says S. Michal Jazwinski, director of the Tulane Center for Aging and professor of medicine at Tulane University. He adds that the award helps balance difficulties that Ohsumi experienced early in his career. Jazwinski and Ohsumi were postdoctoral fellows together in the 1970s in Gerald Edelman’s group at Rockefeller University. Edelman was awarded a 1972 Nobel Prize for work on the immune system.
Jazwinski says that when he arrived in the lab in 1975, Ohsumi was already there. “At that time in the Edelman lab,” Jazwinski says, “we were all focusing on how cells interact with other cells. One of models was recognition of egg by sperm, but Yoshinori was the only person working on that project. It was a bit of a struggle and wasn’t terribly exciting for him.” For his own project, Jazwinski took a new direction that changed his career and Ohsumi’s.
Jazwinski’s original project was studying how agents that bind to the surface of tissue culture cells trigger a series of responses that lead to DNA replication. “We now call that ‘signal transduction,’” he says. Seeking better methods, Jazwinski recalled a seminar by Lee Hartwell, who won a 2001 Nobel Prize for characterizing the cell cycle using yeast mutants. The Edelman lab didn’t work with yeast, so Jazwinski set up yeast genetic experiments from scratch, starting with store-bought yeast.
Ohsumi and Jazwinski now shared a bond – their differences. “We didn’t have much in common with others in lab or each other,” Jazwinski says, “but we were doing something different from everyone else, so I think that’s why we gravitated to each other.” Ohsumi and his wife and toddler son lived in the same building as Jazwinski, so the two scientists also socialized.
“I introduced him to working with yeast,” Jazwinski says, “and he enjoyed it. A year or two later he went back to Japan, got more experience with yeast, and started working on autophagy.”
Jazwinski learned of the Nobel when a Japanese reporter surprised him by calling for comments on the morning of the announcement. He was “delighted” and “elated” for his friend. “The work Yoshinori did was extremely important,” Jazwinski says. “The work Yoshinori did was extremely important,” Jazwinski says. “People saw autophagy by microscopy in the 60s and 70s but didn’t know what was going on. Yoshinori opened up autophagy as field of study and exploited tools that he created to define the molecular mechanism. That’s a big deal.”
Applications of autophagy
The human applications of a process discovered using yeast are hard to imagine. Jazwinski’s research, though, is a prime example of the connection between yeast and human cells. Jazwinski’s group works on aging, applying both yeast genetics and analyses of human population-based data. Although Jazwinski does not directly study autophagy, he uses Ohsumi’s yeast autophagy mutants to identify what limits a cell’s ability to divide indefinitely, a critical factor in human aging.
Ohsumi himself shows no signs of stopping. In the Nobel Media interview, he said, “I believe there are fundamental functions of the cells should be conserved from yeast to mammals.” He hinted that he’ll continue researching those similarities. “Still we have so many questions,” he said. “Even now we have more questions than when I started.”
Award: Nobel Prize in Physiology or Medicine
Born: 1945, Fukuoka, Japan
Affiliation at the time of the award: Tokyo Institute of Technology, Tokyo, Japan
Career: Undergraduate student, the University of Tokyo (1963-1967), Graduate student, Department of Biochemistry, the University of Tokyo with Prof. Kazutomo Imahori (1967-1972), Research Fellow, Department of Agricultural Chemistry, the University of Tokyo (1972-1974), Postdoctoral Fellow, Rockefeller University (1974-1977) with Prof. Gerald M. Edelman, Research Associate, Department of Biology, the University of Tokyo (1986-1988), Associate Professor, Department of Biology, the University of Tokyo (1988-1996), Professor, Department of Cell Biology, National Institute for Basic Biology (1996-2009), Professor, The graduate university for advanced studies (2004-2009), Professor, Advanced Research Organization, Tokyo Institute of Technology (2009-2010), Professor, Frontier Research Center, Tokyo Institute of Technology (2010-2016), Honorary Professor, Tokyo Institute of Technology (2014-present), Professor, Institute of Innovative Research, Tokyo Institute of Technology (2016-present).