Medicine and Phisiology
James E. Rothman
Randy W. Sheckman
Thomas C. Südhof
H. Goren. © HHMI
© Yale University
© S. Fisch
Imagine a cell. It is almost like a city with organelles acting as important buildings with the nucleus as city hall. The roads that keep the cell together are the microtubules and along them drive the cars. Until very recently humans did not know much about these microscopic cars called vesicles, and much of our newfound knowledge comes from this years Nobel Prize winners in Medicine.
The Nobel Prize for Medicine and Physiology went jointly to 2 American professors, and one German professor. Dr. Rothman, Dr. Schekman, and Dr. Südhof.
Vesicles, “storage compartments” made out of membrane, are part of a complicated process of the delivery of molecules, which the cells need. Vesicles carry enzymes and hormones to the surface of the cell, and are also responsible for the activation of nerves. The cell's cars travel on microtubules which are self constructing roads which zip together to form pathways for these vesicles. Before the seventies, the inner workings of this complicated transport system were mostly unknown. Key questions included what genes were responsible, how the vesicles ended up in the right place, and how they docked with target membranes.
Dr. Schekman identified those genes controlling vesicle traffic using a brilliant technique. He used yeast cells as models and looked at cells where vesicles had gone astray and were not reaching target areas. He then compared the genes of those cells to the genes of cells where vesicle traffic was smooth. He pinpointed certain genes which controlled the traffic and even went so far as to identify 3 specific groups of genes which controlled different parts of the traffic system. The biotechnology community quickly utilized his research to genetically modify yeast cells to produce larger amounts of substances like insulin.
As a child Schekman’s dad ,an engineer, got him interested in science and math, and soon Schekman was wining science fairs . He caught a bug for competitive science; however, it was his sister's death from leukemia which drew him close to biology. After college at UCLA he earned a Phd. at Stanford University under the guidance of Arthur Kornberg a famous biochemist. In 1967 his quest for the Nobel Prize began in 1976 when he started his research on yeast cell vesicles at Berkeley. He eventually discovered over 50 genes responsible for vesicle traffic. He moved to Howard Hughes Medical Center in 2002. It was just a few months ago when he received the call from the Nobel Foundation before work. He says he was sleeping when he received the prize and soon after started dancing and saying “Oh My God, Oh My God!” His discoveries were with yeast cells but many of the genes also are in human cells as confirmed by later research.
Dr. Rothman a biology professor at Yale. Studied the proteins which allow for the docking of vesicles while working at Stanford. Rothman found that when vesicles and target membranes meet, the proteins, on both lock together to allow passage of molecules between the two. Similar to antibodies the two proteins on the vesicle only “click” with certain proteins on the “target” membrane and allow the transfer of molecules essential to all life.
Rothman was obsessed with theoretical physics when he was a teenager but near the end of high school he discovered his love for biology. He eventually found a home at Stanford where he followed in the footsteps of Rothman and studied vesicle transport. He says that at the time when he started the research people thought he was nuts, and that it it was impossible to uncover the mysteries of cellular machinery. He continued to pursue his research because of inspiration he got from Arthur Kornberg (Rothman's Mentor) who was there with Rothman at Stanford. Rothman likes to imagine the cell as a complicated machine. “One of the major lessons in all of biochemistry and cell biology is that when proteins operate at the subcellular level they behave in a certain way as if they were mechanical machinery. Its absolutely fascinating!”
Thomas Sudhof was also working at Stanford when he made some of his discoveries that won him the Nobel Prize. He looked at vesicles in the brain and the molecules which are transported between neurons. Before his discoveries, there were very rough details on how the brain moves molecules between cells. He discovered the molecules that trigger the movement of vesicles between the cell. Calcium binds with certain proteins of the neurons which triggers vesicles to transfer between cells.
This is not the first time Sudhof worked on a Nobel Prize discovery. As a postdoc he worked under Michael Brown and Joseph Goldstein who won the Nobel medicine prize in 1985 for discovering receptors involved in cholesterol metabolism. His reaction to the prize was the most priceless as he repeatedly exclaimed “are you serious” to Nobel Media and was almost brought to tears driving in Spain.
The complex machinery which Sudhor, Rothman, and Schekman discovered is essential to understanding the cell. Without vesicles it would be impossible for molecules essential to life to reach where they are needed. Without transportation we can’t have a city and without vesicles you can’t have a cell.