F
OR THEIR DISCOVERIES related to the machin-
ery that regulates the cellular transport system, which is critical to cell functioning, James E. Rothman, Randy W. Schekman, and Thomas C. Südhof were awarded the 2013 Nobel Prize in Physiology or Medicine. Cells move molecules around using tiny MOLECULAR MACHINERY Multiple proteins membrane-enclosed packages called vesicles. (orange and purple) control fusion of a vesicle (blue This year’s Nobel Laureates, who will share sphere) to a cell membrane. the $1.2 million prize, discovered how cells get those vesicles to their intended destination at the intended time. The three winners discovered different aspects of the system. Schekman discovered a set of genes required for vesicle transport. Rothman determined the proteins that allow vesicles to fuse with their targets and thus transfer materials. Südhof discovered the signals that tell vesicles when to release their cargo. totagmin-1 acts as a calcium sensor during synaptic fuSchekman, a cell biologist at the University of Calision. Complexin acts as a clamp during synaptic fusion fornia, Berkeley, developed a genetic screen of the yeast to make sure that regulated exocytosis occurs instead Saccharomyces cerevisiae to determine the genes that of the vesicle simply being incorporated into the cell regulate vesicle trafficking. By using yeast with defecmembrane. tive transport systems, he was able to determine where Glitches in vesicle transport are associated generally vesicle traffic backed up. With this information, he with some human diseases, such as diabetes. Mutations identified 23 key genes, which can be divided into three in genes associated with the protein machinery are classes that control vesicles at the Golgi complex, the involved in specific diseases. For example, mutations endoplasmic reticulum, or the cell surface. in one of the genes are involved in certain forms of Rothman, a cell biologist at Yale University, deterepilepsy.—CELIA ARNAUD
Rothman U OF CALIFORNIA, BERKELEY
prize for work on vesicle transport
Schekman LASKER FOUNDATION
AWARDS: Three U.S. researchers share
mined that proteins known as SNARE (soluble N-ethylmaleimide-sensitive factor-activating protein receptor) allow vesicles to fuse with their target membranes. These proteins had already been discovered by others, but their function was unknown. Rothman determined that these proteins interact with high specificity: The SNARE protein on a particular target membrane is able to interact with only one or a few vesicle SNARE proteins. Südhof, a biochemist at Stanford University, identified the genes that are responsible for controlling the timing of vesicle fusion, particularly those involved in the release of neurotransmitters. He discovered how calcium regulates neurotransmitter release and that two proteins—complexin and synaptotagmin-1—are key players in calcium-mediated vesicle fusion. Synap-
NOBEL COMMITTEE
2013 NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE
YALE U
NEWS OF THE WEEK
Südhof
PHARMACEUTICALS Boehringer Ingelheim to close Ohio drug-manufacturing plant Boehringer Ingelheim, the German pharmaceutical company and contract manufacturer, will close its entire Ben Venue Laboratories operation in Bedford, Ohio, by the end of 2013. In August, the firm said it would close part of the facility and cut 400 jobs. The full closure will affect 1,100 employees. One of Ben Venue’s major products is Johnson & Johnson’s anticancer drug Doxil, a nanoscale liposomal form of doxorubicin. In late September, J&J warned about likely supply shortages this fall; the shortages may now extend into
2014. The Food & Drug Administration did approve a generic version of Doxil from India’s Sun Pharmaceutical Industries in February. Boehringer has struggled to keep the Ohio site open after a series of drug quality problems and has been operating since January under a consent decree with FDA. “Despite the ongoing support of the U.S. Food & Drug Administration, the tremendous dedication of employees, and significant investments in facility upgrades, the company cannot return to sustainable production,” Boehringer says.
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Given the facility’s age and condition, further improvements would require significant additional investment beyond the $350 million already spent to “overcome the systemic manufacturing challenges.” Keeping the site open also would cost the firm about $700 million over the next five years. Boehringer says it has notified FDA of its decision and is working to minimize the impact on patients. In particular, the company is looking at ways to continue supplying sterile injectable drugs now made at the plant.—ANN THAYER
