The Nobel Prize for Medicine this year went to Dr. Yoshinori Ohsumi of the Tokyo Institute for Technology for his work on autophagy, the process of digesting unneeded or damaged cellular components. This process plays a role in many central cellular activities, with applications ranging from genetic to infectious diseases in microbes, plants, and animals. Dr. Ohsumi’s work to uncover the genes required for autophagy has relied on many model organisms, including the model microbe Saccharomyces cerevisiae. His work was published broadly, including in journals published by ASM. Some of these publications uncovered novel mechanisms or interactions. We spoke with Dr. Roger Davis, the Editor-in-Chief of Molecular and Cellular Biology, about the importance of Ohsumi’s research, and the role of basic research in medical applications:
ASM: The first question is a hot topic. Is it auto-phagy or au-toph-agy?
Roger Davis: That’s the million dollar question! I’ve actually never figured that one out. I use both: I usually use au-toph-agy, but there’s no universal consensus.
ASM: Please tell me the importance of autophagy, what it is, and why this work is deserving of the Nobel Prize?
RD: The work absolutely deserves the Nobel Prize! This is really fundamental cell biology. It’s the way the cell has of doing quality control of the makeup of the cell, of getting rid of bad parts or bad organelles of the cell.
Autophagy is something that applies to many diseases. For example, during infection, autophagy is one of the methods the cell uses to get rid of bacteria from the cell.
It’s also involved in neurodegenerative disease. In many diseases, like Alzheimer’s and Parkinson’s, there are problems with quality control within the cell – either getting rid of aggregates or getting rid of things like mitochondria (the powerhouses of the cell that drives metabolism of the cell). When that goes wrong, you end up with neurodegeneration and autophagy is really part of those mechanisms.
Autophagy also involved in diabetes and metabolism in general, not only in fitness of mitochondria but also the way we metabolize fats in the liver. Autophagy is one of the ways we digest and metabolize our fats, so it’s very important for situations like diabetes.
Finally, for cancer, there are many tumor cells that actually require autophagy as a way of surviving. Not for all types of cancer, but for some types of cancer, drugs that can interfere with autophagy are actually sufficient to kill tumor cells. Many individuals are now working on autophagy as a way of curing cancer.
I think it’s incredible that a very basic finding in cell biology was discovered subsequently to be relevant in numerous diseases. Autophagy is currently a very active area of research.
ASM: How did microbes help to uncover some of these processes?
RD:Dr. Ohsumi exploited a genetically tractable model system – bakers yeast – to understand mechanisms of protein degradation. His early work published in the Journal of Bacteriology on the yeast vacuole set the stage for subsequent genetic analysis of autophagy. The finding that the yeast genes that control autophagy are highly conserved in humans validates the importance of microbial studies for providing insight into human disease.
For my own journal (Molecular and Cellular Biology), we focus on cell biology. The work that MCB has published has been in Dr. Ohsumi’s original fundamental work in defining the genetics of autophagy in yeast and discovering all the genes involved in this pathway; it turns out there are a large number of them! Subsequent work he did has demonstrated the work that came from the original microbiology with yeast also applies to mammalian cells, to human cells, and that work has appeared in MCB.
ASM: What do you think the prize says about the role of basic research?
RD: I think winning the Nobel Prize for this particular research reinforces the notion that basic research is really the foundation for medical science. It’s very difficult to predict where the roles of basic research are. For example, in the case of autophagy, it wasn’t known that autophagy was really important for all of these human diseases. It was really the groundbreaking work of Dr. Ohsumi to define the genetics of the pathway that really allowed the work to be applied to humans that it then became apparent.
This is something that is true in many Nobel Prizes awarded, that the basic research has been fundamental to what has come afterward. I’m thinking a few years ago, at my own institution, there was a Nobel Prize awarded for the discovery of small RNA regulators of gene expression, RNAi, and that set up a whole field of using RNAi-based approaches for therapy directly in humans. I think the work that was originally done without anticipation that this would be an application, but without the basic research, none of these advances would be made.
ASM: Beautifully said.
RD: When I heard Ohsumi had won the Nobel Prize, I was very excited about it. I think it is wonderful that somebody who did really pioneering work on the genetics of the process in yeast can actually win the Nobel Prize based on the fundamental importance of that contribution and how it applies to an entire field. I think it’s rewarding to know that these pioneering individuals are really being recognized for the contributions that they’re making. It made me very excited when I heard the news. I am also really happy that ASM was able to support the publication of some of this pioneering research.