The Nobel Prizes are back! This week, which is Christmas for scientists (though, it must be said, only some of us), will see the awards for Physiology or Medicine, Physics, and Chemistry bestowed on some of the top scientists in the world. Given the significance of the awards and the tremendous amounts of work and insight they represent, I’d like to explain the basics of the science behind each award, starting with the prize for Physiology or Medicine.
The Swedish Academy announced Dr. Yoshinori Ohsumi as the winner of the Nobel Prize for Physiology or Medicine on October 3rd. Dr. Ohsumi discovered the genetic underpinnings of a cellular process called autophagy in the late 1980’s, an effort that led to intense research in the field which has applications from cancer to aging. To get some inside information about the process, I spoke with my friendly neighborhood autophagy researcher (autopho-bro?) Ricky Antonia, a graduate researcher at UNC Chapel Hill who studies autophagy as part of his doctoral work.
The word autophagy derives from Greek words meaning “self eating,” which is an appropriate name for a process that occurs in response to stress, particularly starvation. When starved, cells undergo autophagy, which recycles cellular components in order to fuel cell survival. To “self eat”, a cell uses membranes to envelop structures such as large aggregates of protein or even mitochondria, separating them from the rest of the cell. These membrane-bound pouches, called autophagosomes, then fuse with another cellular structure, called the lysosome. Acting as a cellular stomach, the lysosome contains acids and proteins capable of breaking down cellular structures. This results in what is essentially digestion of the cellular components contained in the autophagosome. The products of this breakdown are lipids, amino acids, nucleotides and sugars- the fuel of cellular metabolism, ready to continue building the cell.
Many human diseases involve autophagy, including cancer and neurodegenerative disorders. According to Ricky, however, its role in cancer is tough to pin down. Autophagy could be beneficial or detrimental, depending on the type of cancer in question. For example, some researchers focus on the potential of autophagy-inducing drugs in the fight against cancer, betting that setting the inherently destructive process of autophagy on overdrive could destroy cancer cells. But, this kind of manipulation is a double-edged sword: by providing tumor cells with extra energy, their growth could speed up instead of slowing down.
The role of autophagy in neurodegenerative disorders, like Alzheimer’s or Parkinson’s, is more straightforward. Alzheimer’s is a disease where large, nonfunctional blobs of protein form in neurons, eventually impeding brain function. Therefore, formation of these plaques may be related to defects in autophagy, which normally dispenses with useless aggregates of protein. Additionally, a mutation in a mitochondrial protein called Parkin causes Parkinson’s by rendering the neuron unable to dispose of nonfunctional mitochondria. As a result, DNA damage builds up, leading to breakdown of neurons.
The future is bright for autophagy. In addition to its recent receipt of the Nobel Prize, the field of autophagy is an active area of research that is broadly understood, and yet remains deeply mysterious. Asked about the most pressing questions for the autophagy field, Ricky quickly responds that the basic science is lacking. Researchers know a lot about the genes involved in autophagy, but genetic methods amount to using a sledgehammer to drive a nail, which does not make for very precise experiments. There is also a dearth of knowledge about the formation of the cellular structures that carry out autophagy, due to the difficulty in visualizing these structures in cells. Finally, simply distinguishing when autophagy “will be adaptive versus maladaptive,” would go a long way to help researchers understand its role in disease.
So far, the story of the 2016 Nobel Prizes is about the importance of basic science in fueling the creation of technology. In the case of autophagy, researchers know a lot, but the function of autophagy is still too squirrely to grasp, keeping therapeutics out of reach. Tomorrow, we’ll see that an esoteric field of math, called topology, may change the way we make electronics and use electricity.
The Inner Life of Life 