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Cell research paves way to treatment

This year, the Nobel Assembly has awarded the 2016 Nobel Prize in Physiology or Medicine to Japanese researcher Yashinori Ohsumi.

His remarkable work focused on understanding how cells eat themselves. Cells are the tiny building blocks that form the tissues and organs that make up our bodies. Using generic baking yeast, he identified the genes responsible for this self-eating process at a cellular level. From there, he worked to understand the different components of the autophagy system and how they work together.

Yeasts have similar but much simpler cellular processes to animals. His work in the humble yeast made it possible to understand autophagy in animals and people, which are infinitely more complex and challenging to study.

The process of self-eating is central to many normal functions in the body. For example, cells ramp up autophagy during times of distress. When the body is going into a state of starvation, autophagy is a way for nutrients to be recycled. By breaking down non-essential cell components, autophagy allows these to be repurposed. It is a survival step that can function as an intermediary or alternative to cellular death.

This process is highlighted by critters that hibernate like bats, bears, and squirrels. Autophagy likely plays a key role in maintaining muscle mass during the long months these animals spend inactive and not eating.

Within cells undergoing self-eating, non-essential components, infectious agents and other cellular waste are wrapped in a membrane. These fuse with other packages containing enzymes and acid, which break down whatever is inside for re-use elsewhere in the cell.

By keeping this all within a membranous package, the cell avoids harming normal components that are functioning well.

Autophagy plays a key role in normal physiological processes. At the end of their lactation, cows undergo a remarkable transformation within their mammary glands. From producing litres of milk to being completely dried off, all those tissues have to change from secretion to regression. Autophagy has an important role in this process.

Optimum changes during the dry period are essential to setting up the mammary gland for high milk yield in the next lactation.

Autophagy has a duel role in infectious diseases. Self-eating can effectively eliminate infectious agents like viruses and bacteria from individual cells. But in some cases, the pathogen can also highjack the autophagy process and use the machinery for its own purposes to enhance infection.

For example, influenza A (the type that infects people, birds and pigs and is responsible for the winter flu season), manipulates the self-eating process by first triggering it but then preventing the recycling step.

This allows viral components to accumulate within the cell and leads to more virus being produced, ultimately enhancing infection. Responses to other infections like bovine viral diarrhea, bovine respiratory disease of feedlot cattle and equine strangles all likely involve the autophagy process.

In cancers, which affect both people and animals, autophagy may have a crucial role in preventing cancer formation. Self-eating recycles damaged proteins and stressed components, which could trigger cancer if allowed to accumulate. But once tumours develop, autophagy may be essential for allowing cancerous cells to survive and proliferate. The environment within a tumour is stressful for cells because there is poor blood supply, yet very fast metabolism that rapidly generates waste.

Self-eating in this situation keeps the cancerous cells alive and well. Autophagy may also explain why some cancers become resistant to chemotherapy.

In human medicine, researchers have linked abnormal autophagy to a suite of neurodegenerative diseases including Alzheimer’s, Huntington’s and Parkinson’s diseases.

These are a few examples of how this discovery has implications for human and animal health. As we learn more about this fundamental biological process, researchers may discover new ways to treat disease and infections.

Dr. Jamie Rothenburger is a veterinarian who practices pathology and a PhD student at the Ontario Veterinary College. Twitter: @JRothenburger

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