A Nobel for Blobel

The 1971 hypothesis, validated experimentally in 1975, that proteins find their way around the cell thanks to a molecular luggage label—the so called 'signal hypothesis'—has earned Rockefeller University professor and Howard Hughes Investigator Günter Blobel the 1999 Nobel Prize for physiology or medicine. Blobel won the Albert Lasker Basic Medical Research Award for this theory in 1993.

It is estimated that a typical cell contains around one billion proteins, which need constant replenishment. Thus, after being manufactured by ribosomes, proteins must be distributed to the appropriate location within the cell—that is, the relevant organelle. Blobel's early work focused on transport through the endoplasmic reticulum. He proposed that the amino-terminal portion of a protein—the first 20 or so amino acids to be assembled—acts as a signal sequence, permitting that protein to attach to a receptor in the membrane of the endoplasmic reticulum, where it opens a channel through which the protein can travel.

This hypothesis has been extended by Blobel and others to protein trafficking to all organelles. It has also been used to explain the molecular basis of some diseases, such as the hereditary condition hyperoxaluria, which causes kidney stones in the young, and a form of hypercholesterolemia. The phenomenon of directing proteins to organelles could also be exploited in the development of drugs that target specific components of the cell known to be faulty. Or it could be used in the production of human therapeutic proteins within complex cell models, such as yeast-biological 'protein factories'.

Blobel moved to Rockefeller University in 1967 to work as a postdoctoral fellow in George Palade's laboratory. Blobel has described Palade, who shared a Nobel Prize in 1974 with Albert Claude and Christian de Duve, as a great mentor and has said, "My work was a direct extension of the work Dr. Palade had started at Rockefeller." Blobel now works on identifying signal sequence channels in other organelles, and on elucidating the movement of large proteins, such as protein-bound RNA or DNA, into the nucleus through nuclear pore complexes.

The signal hypothesis

As with all scientists who reach the top of their field, stories about Blobel's character within the laboratory abound. Many wonder why his signal hypothesis colleague, David Sabatini, did not share the prize, and some mention Cesar Milstein's 1972 paper showing that immunoglobulin expresses a transient signal sequence. However, Blobel supporters outweigh detractors, and in addition to winning the last Nobel Prize in physiology or medicine of this millenium, Blobel is credited with having nurtured generations of scientists who will become leading cell biologists in the next millenium.