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Biochemist Peter Walter Receives 2018 Breakthrough Prize in Life Sciences

By Pete Farley | | December 3, 2017

Biochemist Peter Walter Receives 2018 Breakthrough Prize in Life Sciences

Peter Walter, PhD, professor of biochemistry and biophysics at UC San Francisco, has been named winner of a 2018 Breakthrough Prize in Life Sciences, for his research on a biological mechanism that normally protects cells, but can cause disease if not functioning properly.

The Breakthrough Prizes, now in their sixth year, were founded by Sergey Brin; Yuri and Julia Milner; Mark Zuckerberg and Priscilla Chan; and Anne Wojcicki. The Prizes are “dedicated to advancing breakthrough research, celebrating scientists and generating excitement about the pursuit of science as a career.” They are given each year in Life Sciences, Fundamental Physics, and Mathematics. As many as five prizes are given in each field, and each prize carries a cash award of $3 million.

Walter, 62, was recognized for “elucidating the unfolded protein response, a cellular quality-control system that detects disease-causing unfolded proteins and directs cells to take corrective measures,” according to the award citation.

Kazutoshi Mori, PhD, a leading researcher at Kyoto University in Japan who has shared many major scientific awards with Walter, also received a 2018 Breakthrough Prize for his work on the unfolded protein response.

Kazutoshi Mori and Peter Walter speak during the Breakthrough Prize ceremony
Peter Walter (right), PhD, and Kazutoshi Mori, PhD, receive their 2018 Breakthrough Prize in Life Sciences during an awards ceremony Sunday night.

“As cell biologists, we decipher the fundamental principles of life,” Walter said while receiving the award at a Breakthrough Prize gala hosted by actor Morgan Freeman at the NASA Ames Research Center in Mountain View, Calif. “It’s a fascinating job to figure out how living cells accomplish these amazing tasks – and from that, we can learn what goes wrong in disease and what goes wrong as we age. Our work increases knowledge with the goal to reduce human suffering. I really thank the founders of this amazing award for shining the spotlight on the value of discovery.”

UCSF Chancellor Sam Hawgood said, “This is an exciting day for Peter Walter and for the University. Over the course of a research career spanning more than three decades, Peter has made seminal discoveries about cellular quality-control mechanisms and the diseases – from cancer to diabetes to Alzheimer’s disease – that may result if these basic processes go awry.

“His work is a perfect example of how decoding the basic principles of life can fundamentally improve our understanding of human health and the critical importance of such fundamental research to our society.”

The Unfolded Protein Response

Proteins, the basic building blocks of the body, start out in the cell as simple, linear chains of amino acids that must be folded like origami into proper three-dimensional shapes before they can be sent off to do their job. Protein folding occurs within a maze-like structure called the endoplasmic reticulum (ER), which also serves as a checkpoint: well-folded proteins exit the ER and are shuttled to their destinations, but malformed proteins – a hallmark of many serious diseases – are targeted for destruction.

screenshot of video
Watch a video explainer, "What is the Unfolded Protein Response?"

If too little ER is present to handle the number of proteins being synthesized – a state known as ER stress – a logjam of unfolded proteins accumulates. Working with yeast in his UCSF laboratory, Walter and colleagues discovered that sensor molecules in the ER membrane detect such stress and trigger the unfolded protein response (UPR), a suite of parallel signals that instruct genes to temporarily slow down protein synthesis while simultaneously increasing the abundance of ER.

But because accumulated unfolded proteins can be a menace, this compensatory role of the UPR has a built-in time limit: If a balance between ER abundance and protein synthesis cannot be restored quickly, the UPR shifts its signaling toward pathways that cause the cell to self-destruct.