Scientists who invented new ways to study how "cargo" is moved within cells and, as a result, discovered a new biological motor protein, kinesin, at the Marine Biological Laboratory (MBL) in Woods Hole, Mass., have received the prestigious 2012 Lasker Award for Basic Medical Research, the Albert and Mary Lasker Foundation announced today. The awardees are Michael Sheetz of Columbia University; James Spudich of Stanford University School of Medicine; and Ron Vale of University of California, San Francisco/Howard Hughes Medical Institute.
The Lasker Awards are among the most respected science prizes in the world, and often anticipate future recipients of the Nobel Prize. Also announced today were the recipients of the 2012 Lasker Award for Clinical Research (Roy Calne and Thomas E. Starzl) and for Special Achievement (Donald D. Brown and Thomas Maniatis). The awards carry a $250,000 honorarium for each category.
"The Lasker Awards celebrate biomedical research that has had a transformative effect on the practice of medicine, science, and the lives and health of people all over the world," says Alfred Sommer, chair of the Lasker Foundation's Board of Directors. "This year's awards are no exception, honoring fundamental biological discoveries, life-saving surgical techniques and scientific statesmanship of the highest order."
Sheetz, Spudich, and Vale opened up the study of "cytoskeletal motor proteins, machines that move cargoes within cells, contract muscles, and enable cell movements.-. The miniscule motors underlie numerous vital processes, and the landmark achievements of Vale, Spudich, and Sheetz are driving drug-discovery efforts aimed at cardiac problems as well as cancer," states the Lasker Foundation announcement.
The Lasker Foundation has provided a detailed description of the trio's discoveries. To hear Vale describe them, see this iBioSeminars video: http://www.ibiomagazine.org/issues/august-issue/molecular-motor-search.html.
A Classic MBL Collaboration
The motor protein discoveries recognized by the Lasker Award coalesced during an intense period of scientific investigation at the MBL (1983 to 1985) involving several labs. Key elements at the MBL were essential to the discoveries, including an abundance of squid, the organism in which the investigations were conducted; the landmark introduction of video-enhanced microscopy at the MBL, independently made by Robert Allen of Dartmouth College and Shinya Inou- of MBL; and an environment dedicated to risk-taking science and collaborations among researchers from all over the world.
"It was fully in the spirit of MBL, in the sense of collaborations without boundaries. The MBL gave us the opportunity to just get down and do the science," says Sheetz.
Vale first became involved in this research as a graduate student at Stanford University in 1982. At the time, Vale was interested in how material is transported inside nerve cells (neurons), which in humans can be more than three feet long. For example, Vale says, "a motor neuron that starts in your spinal cord, where its nucleus and DNA reside, extends a long, thin tube called an axon all the way to your foot, where it can stimulate a muscle to contract. Inside the axon, building blocks such as proteins that are made in your spinal cord have to be continually shipped to your foot, to keep the nerve cell alive and functional. And very little was known about this transport process in the 1980s."
Vale had been inspired by two landmark 1982 papers by Robert Allen, Scott Brady, and Ray Lasek in which they used Allen's video-enhanced microscopy to make movies of axonal transport in the squid. The squid has what Vale calls "the granddaddy of all axons," being over 100 times larger in diameter than a human axon. Video-enhanced microscopy dramatically increased the contrast of the images, allowing one to see details that could never be seen before. "What they saw was absolutely fantastic," Vale says. "All these little dots [organelles] zipping along the axon, moving between the cell body and the nerve terminal. It was really thrilling to watch."
Meanwhile, in a lab downstairs at Stanford, Spudich and Sheetz (who was on sabbatical from University of Connecticut) were successfully developing a way to study the motion of myosin-a motor protein known to cause muscle movement-in a test tube. Vale was intrigued by their research, and began to wonder if axonal transport might be explained by a similar myosin mechanism. He and Sheetz decided to test out the idea in the squid giant axon.
But 1983 was a year of El Ni-o, and not a squid was to be found in the warm waters off California. So Sheetz and Vale came to the MBL, where there was plenty of squid from the cold Atlantic. Originally they collaborated with Allen's and Lasek's labs, but by the end of the summer they had teamed up instead with Tom Reese and Bruce Schnapp of the National Institutes of Health, who had a year-round lab the MBL. All of these labs were working intently on axonal transport, and all made important contributions to the final picture. (For a detailed scientific discussion, see Salmon, ED, Trends Cell Biol. 1995 Apr; 5(4):154-8.)