The "logistics" mechanism in the cell
How cells sort, package, and deliver large amounts of material during metabolism, three Nobel laureates have discovered that the key is the vesicle transport system.
Under a microscope, neurons look like tiny folds of paper crumpled and spread, and they communicate by synapses, which are the basis of what the human brain can do. Thomas Sudhof, a neuroscientist at Stanford university, is interested in figuring out how the "communication" between neurons works.
On October 7, 2013, the Nobel Prize website put the phone on Mr. Sudekhov's mobile phone while he was driving on the road in Spain. At first he thought it was his colleague calling to show him the way, so he pulled into a parking lot to answer the phone, but it turned out to be a call from Sweden.
Before that, the staff of the Nobel Prize website called the home of sudehov, but he was not at home. The phone rang three times before his wife, Chen lu, decided to go downstairs and answer it, thinking it was a Chinese relative who was confused by the time zone.
The royal Swedish academy of sciences announced the award of the Nobel Prize in physiology or medicine in 2013 to three scientists who have made outstanding contributions to the study of "cellular material transport" -- James Rothman and Randy Schekman of the United States, and Thomas Sudhof of Germany.
Although he did not work with the other two, the trio solved one of biology's big questions: "how cells metabolise large amounts of material to sort it out, package it and deliver it to the right place at the right time". The three Nobel Prize winners have shown that the problem lies in the vesicular transport system within cells.
The physical logistics network
Just as a modern logistics network can deliver goods to thousands of homes, a similar transport system is needed to transport molecules produced by cells, such as hormones, neurotransmitters and cytokines, to other parts of the cell or out of the cell.
Forty years ago, George Palade, a renowned cell biologist and Nobel laureate in physiology or medicine, discovered the intracellular transport network under an electron microscope. And what he found was that there was a tiny vesicle that was wrapped in a membrane, a vesicle. These vesicles can travel between the organelles with cellular cargo or fuse with the cell membrane to release the cargo outside the cell. The presence of vesicles effectively prevents the intermingling of different types of cellular cargo in different locations.
The discovery was quickly accepted by most scientists, but with it came a more complex question: "how do these vesicles know when and where to deliver the goods".
In 1976, shukman of the university of California, Berkeley, set up a laboratory and began to explore the problem in an unusual way. Yeast was used as a model animal to study the mechanism of material transport system in cells. At the time, some colleagues thought his research was a "stupid decision".
Through genetic screening, he found a yeast cell with a faulty transport system, in which vesicles accumulate in parts of the cell, as if the collapse of a logistics network had caused cargo to pile up. He found that mutations in certain genetic genes caused defects in the yeast cells.
Using these genes as a breakthrough, and after 10 years of research, shukman identified three genes that regulate vesicle transport at different stages, providing a new insight into the mechanisms of material transport systems.
In the earliest days, shukman's work on yeast was regarded as not only foolish by some, but often underappreciated. But his research has turned out to be extremely valuable. In the 1980s and 1990s, many drugs were developed thanks to his work on yeast. To this day, one-third of the world's insulin comes from yeast.
At the same time, rothman set up his own lab at Stanford, using mammalian cells for similar experiments. He found a protein that affects the transport of cellular material, and the gene that encodes it corresponds to the mutated gene shukman found in yeast, suggesting a common evolutionary origin of the vesicle transport system.
In addition, rossman found a protein complex that enables vesicles to dock and fuse with the membrane system of their destination. To ensure that the goods are delivered to a precise location, they will only bond in a specific way. The findings shed light on how vesicles transport to targets.
The findings have long made shukman and rothman the favorites for the Nobel Prize. In 2002, they won the American lasker prize. Many of the winners of this prize will later receive a Nobel Prize, and it is often used as a kind of pointer. The two biologists are no exception, both expecting a call from Stockholm in October of a certain year.
In a news release, the university of California, Berkeley described how, every year, shukman and rothman would call each other when the expected morning came and went, with no Swedish telephone. Shukman calls it groundhog day, to borrow a phrase from the movie. In the film groundhog day, the hero repeats the same story every day.
These days repeat for ten years. On the night of Oct. 6, 2013, shukman returned home from Germany with one of the country's highest awards in biochemistry. After lying down for a few hours, he heard his wife holding the phone and Shouting, "here comes the phone! It's a call! It was the year Sweden finally called. "Oh my god." Shukman said it was his first reaction, and "my second reaction was this, too."