Nobel Laureate GŁnter Blobel Visits NIH
By Dr. Harrison Wein
Dr. GŁnter Blobel, the 1999 Nobel Laureate in Physiology or Medicine, began his talk in the NIH Director's Wednesday Afternoon Lecture Series on Mar. 1 with a history lesson. By way of explanation, he said that much of the work that led to his Nobel Prize is not on the Internet and may be hard for younger people to trace. "I thought some people in the audience may say, 'Well, what the hell did he get the Nobel Prize for?'"
It is doubtful that many in the packed house were asking that question. Blobel's discoveries opened the door for a flurry of research that biologists and biomedical researchers now make use of every day. The biotechnology industry owes a great debt to him as well, routinely using his discoveries to enable medicines to be manufactured within cells. Blobel and his team were able to answer one of the fundamental questions of cell biology: how are proteins in the cell delivered to their final destinations?
Back in 1971, he first proposed the "signal hypothesis" to explain how the cell directs its proteins across the membranes of its various internal compartments (the endoplasmic reticulum, the nucleus, mitochondria, etc.). He explained his hypothesis, "In the protein, there is a discrete sequence, an intrinsic signal built into the protein which directs the protein across these various membranes." Blobel's hypothesis turned out to be correct, and he has now spent almost 30 years studying signaling sequences, along with the molecules that recognize them and that help the proteins containing them to reach their destinations.
His laboratory began by studying how proteins cross the membrane of the endoplasmic reticulum. The first protein discovered in this process was the signal recognition particle (SRP). The SRP recognizes a unique signal sequence in a protein and then brings it to the surface of the endoplasmic reticulum, where it binds a protein called the signal recognition particle receptor. There the protein then moves through a protein-conducting channel into the endoplasmic reticulum.
"The endoplasmic reticulum work has sort of been the catalyst for all the other organelles," Blobel said. Signal sequences were subsequently found for entering into mitochondria and into peroxisomes. Now, Blobel explained, "there is a whole group of signal sequences that have been discovered which address the proteins to these various membranes."
He is now focusing his efforts on examining how proteins are transported into and out of the nucleus, and he spent much of his talk describing this process. Small proteins can diffuse into and out of the nucleus without a signal sequence, but larger proteins need help getting through what is called the nuclear "pore." Yeast serves as a good model system for these studies and many, if not all, of the proteins that make up the yeast nuclear pore complex have now been identified. A host of molecules that assist in nuclear transport and recognize its signal sequences have been identified as well. While many scientists refer to these molecules as "importins" and "exportins" depending on their function, Blobel prefers the more general term "karyopherins," since some of these molecules seem to be involved in both nuclear import and export.
Blobel concluded his talk by describing how he is using his $960,000 in Nobel Prize money. "I've devoted my Nobel prize to the reconstruction of two monuments in Dresden," he explained. Only 4 days after Blobel's mother had shown him the architectural beauty of Dresden, he watched from afar as Allied forces bombed the city in 1945. He was only 8 ½ years old, and the sight made a deep impression on him. Now, in addition to his scientific contributions to the world, he is finally helping, he said, to "restore the grandeur of the Dresden skyline."
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