The Noble Prize 2016 In Physiology or Medicine Awarded to Yoshinori Ohsumi of Japan 0 781

The Noble Prize 2016 In Physiology or Medicine Awarded to Yoshinori Ohsumi of Japan 0 782

The 71-year-old Japanese scientist won the prize on Monday for his work on how damaged cells recycle themselves — known as autophagy — and the major implications it has for health and diseases, including cancer and neurological disorders.

Degradation – a central function in all living cells
Our cells have different specialized compartments. Lysosomes constitute one such compartment and contain enzymes for digestion of cellular contents. A new type of vesicle called autophagosome was observed within the cell. As the autophagosome forms, it engulfs cellular contents, such as damaged proteins and organelles. Finally, it fuses with the lysosome, where the contents are degraded into smaller constituents. This process provides the cell with nutrients and building blocks for renewal.

But Ohsumi’s field of interest was far from the limelight when he started his career. Autophagy is a process whereby cells ‘eat themselves’ — which when disrupted can cause Parkinson’s and diabetes.

Born in southwest Fukuoka near the end of World War II, Ohsumi was initially interested in chemistry, but switched his focus to molecular biology, according to a 2012 interview. Ohsumi, the youngest of four brothers, received his PhD from the University of Tokyo in 1974 and spent several years at Rockefeller University in New York before coming back to Japan in the late 1980s. He has been a professor at the Tokyo Institute of Technology since 2009.

Yoshinori Ohsumi Japan

Winning the Nobel “was my childhood dream, but it has not been the focus of my concern since I got into research — I don’t like competing”, Ohsumi told a press briefing in Tokyo Monday evening.

“I have fun doing what others don’t do, rather than something that everybody is flocking to.”

In what the jury described as a “series of brilliant experiments in the early 1990s”, Ohsumi used baker’s yeast to identify genes essential for autophagy. His findings opened the path to understanding the importance of autophagy in many physiological processes, such as how the body adapts to starvation or responds to infection. When autophagy breaks down, links have been established to Parkinson’s disease, type 2 diabetes and other disorders that appear in the elderly. He then went on to explain the underlying mechanisms for autophagy in yeast and showed that similar sophisticated machinery is used in human cells.

“Autophagy has been known for over 50 years but its fundamental importance in physiology and medicine was only recognised after Ohsumi’s paradigm-shifting research in the 1990’s,” the Nobel jury said Monday.

Researchers first observed during the 1960s that a cell could destroy its own contents by wrapping them up in membranes and transporting them to a degradation compartment called the lysosome — a discovery that earned Belgian scientist Christian de Duve a Nobel Medicine Prize in 1974. It was de Duve who coined the term “autophagy”, which comes from the Greek meaning self-eating. Ohsumi was able to build on de Duve’s work and prove that the lysosome “wasn’t a waste dump, it was a recycling plant,” Karolinska Institute professor Juleen Zierath explained.

hsumi studied thousands of yeast mutants
In yeast (left panel) a large compartment called the vacuole corresponds to the lysosome in mammalian cells. Ohsumi generated yeast lacking vacuolar degradation enzymes. When these yeast cells were starved, autophagosomes rapidly accumulated in the vacuole (middle panel). His experiment demonstrated that autophagy exists in yeast. As a next step, Ohsumi studied thousands of yeast mutants (right panel) and identified 15 genes that are essential for autophagy.

“Mutations in autophagy genes can cause disease, and the autophagic process is involved in several conditions including cancer and neurological disease,” The jury added. Intense research is now under way to develop drugs that target autophagy in various diseases.

The prize comes with eight million Swedish kronor (around $936,000 or 834,000 euros).

“This is the highest honour for a researcher,” Ohsumi told Japan’s public broadcaster NHK. “My motto is to do what others don’t want to do. I thought (cellular breakdown) was very interesting. This is where it all begins.”

mechanism by which proteins and protein complexes promote distinct stages of autophagosome formation
Ohsumi studied the function of the proteins encoded by key autophagy genes. He delineated how stress signals initiate autophagy and the mechanism by which proteins and protein complexes promote distinct stages of autophagosome formation.

“It didn’t draw much attention in the past, but we’re now in a time when there is a bigger focus on it,” added Ohsumi. In response to questions, he said he was worried about budget cutbacks in scientific research, adding that it is fun doing research without knowing where things will go.

However, the medicine prize is awarded by the Nobel Assembly at the Karolinska Institute, which has seen a shadow cast over its reputation following a recent scandal involving Italian surgeon Paolo Macchiarini. In 2011, while working as a visiting professor at Karolinska, Macchiarini soared to fame for inserting the first synthetic trachea, or windpipe, using patients’ stem cells. His work was initially hailed as a game-changer for transplant medicine. But two patients died and a third was left severely ill.

Allegations ensued that the risky procedure had been carried out on at least one individual who had not, at the time, been critically ill, and in 2014 several surgeons at Karolinska filed a complaint alleging that Macchiarini had downplayed the risks of the procedure. Karolinska suspended all synthetic trachea transplants shortly after and fired Macchiarini. Two members of the Nobel medicine prize assembly were forced to step down in September over the scandal.

The 2016 Nobel season continued on Tuesday with the physics prize announcement, with the discovery of gravitational waves seen as a potential winner. The first observation of gravitational waves was announced in February 2016, a major research breakthrough that confirms one of Albert Einstein’s predictions in his theory of general relativity. The chemistry prize, to be announced on Wednesday, could go to classic research in the field, with speculation pointing to researchers who added new elements to the periodic table, such as nihonium or moscovium.

On Friday, all eyes will turn to Oslo where perhaps the most prestigious of the awards, the peace prize, will be announced. The Norwegian jury has sifted through an avalanche of nominations this year — a record 376, almost a hundred more than the previous record from 2014. Among those often cited as likely winners are the architects of two historic accords: The recent peace deal in Colombia between the government and the leftist FARC rebels; and the Iranian nuclear deal. But in a shock upset, Colombians on Sunday voted against the peace deal by a razor-thin majority in a referendum.

The economics prize will be announced on 10 October, and the literature prize wraps things up on 13 October.

Key publications

Takeshige, K., Baba, M., Tsuboi, S., Noda, T. and Ohsumi, Y. (1992). Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. Journal of Cell Biology 119, 301-311

Tsukada, M. and Ohsumi, Y. (1993). Isolation and characterization of autophagy-defective mutants of Saccharomyces cervisiae. FEBS Letters 333, 169-174

Mizushima, N., Noda, T., Yoshimori, T., Tanaka, Y., Ishii, T., George, M.D., Klionsky, D.J., Ohsumi, M. and Ohsumi, Y. (1998). A protein conjugation system essential for autophagy. Nature 395, 395-398

Ichimura, Y., Kirisako T., Takao, T., Satomi, Y., Shimonishi, Y., Ishihara, N., Mizushima, N., Tanida, I., Kominami, E., Ohsumi, M., Noda, T. and Ohsumi, Y. (2000). A ubiquitin-like system mediates protein lipidation. Nature, 408, 488-492

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