More than two decades of research into protein folding have led to a Lasker award for Arthur L. Horwich, M.D., HS ’78, Sterling Professor of Genetics and professor of pediatrics, and his colleague Franz-Ulrich Hartl, M.D., of the Max Planck Institute of Biochemistry in Germany. In September the two were named co-winners of the 2011 Albert and Mary Lasker Basic Medical Research Award for their discoveries of how proteins are assisted in folding in the cell.
Proteins, which emerge single-file in a chain of amino acids from cellular structures called ribosomes, are crucial to the function of all life but become biologically active only when they fold into complex, origami-like structures that depend on their amino acid sequence. Scientists used to think that proteins assumed the correct shape on their own. In the late 1980s, Horwich and Hartl began the research that showed that proteins fold in the cell with the assistance of specialized proteins called chaperonins.
Improper folding, scientists now know, can cause proteins to clump together, a process implicated in such neurodegenerative illnesses as Parkinson disease, Alzheimer disease, Huntington disease, mad cow, and amyotrophic lateral sclerosis.
“We had a hard time believing there was such a thing as a folding machine when our initial genetic work suggested it in the late 1980s, but 20 years of work have allowed us to see the chaperonin machine at X-ray structural resolution and dissect how it works,” said Horwich, a Howard Hughes Medical Institute investigator. “Nature has come up with something amazingly beautiful to help proteins fold inside the cell.”
This is not the first honor for Horwich. He received the Gairdner International Award in 2004, the Wiley Prize in Biomedical Sciences in 2007, the Rosenstiel Award for Distinguished Work in Basic Medical Science in 2008, and the Louisa Gross Horwitz Prize in 2008.
The Lasker awards, which carry an honorarium of $250,000 for each category, were presented at a ceremony on September 23 in New York City. Since the inception of the Lasker Awards in 1945, 80 Lasker laureates have gone on to win the Nobel Prize.
“Art is a spectacular researcher with an extraordinary commitment to science,” said Dean Robert J. Alpern, M.D., Ensign Professor of Medicine. “His keen intellect led us to a new understanding of one of biology’s basic questions: How do proteins fold into their precise shapes?”
In addition to Horwich, two current Yale faculty members have won Laskers: James Rothman, Ph.D., the Wallace Professor of Biomedical Sciences, professor and chair of cell biology, and Vincent DeVita, M.D., the Joseph and Amy Perella Professor of Medicine at Yale Cancer Center. Both men were honored while working at different institutions.
For more on Arthur Horwich and protein folding, see “Getting the right fold,” Yale Medicine, Fall/Winter 2004.