Chapman appointed Howard Hughes Investigator

Edwin Chapman, a professor of physiology at the Medical School, has been named an investigator of the Howard Hughes Medical Institute (HHMI), the institute announced today (March 21).

Chapman and 42 others were chosen from among some 300 scientists in a nationwide competition of candidates who demonstrate “exceptional promise within four to 10 years of their becoming independent scientists.”

Appointment to the HHMI is considered to be one of the most prestigious in biomedical research. Chapman joins three other researchers who are HHMI investigators: Sean Carroll, professor of genetics; Judith Kimble, professor of biochemistry and medical genetics; and Paul Ahlquist, professor of molecular virology and plant pathology.

“This is a great honor for Ed and for the university,” says Chancellor John Wiley. “Howard Hughes Medical Investigators are highly coveted appointments that help researchers make bold advances their fields. We look forward to seeing more great work from Chapman’s lab.”

Chapman has been a physiology professor at UW since 1996. He studies elements of the synapse, the junction between pre-synaptic neurons, which store and dispatch messages in the form of chemical neurotransmitters, and post-synaptic neurons that receive them. In addition to being essential to interaction between nerve cells, synapses also are responsible for communication between nerve cells and muscle cells and for the release of hormones.

The largest private philanthropy in the United States, the Howard Hughes Medical Institute is a medical research organization based in Chevy Chase, Md. Founded in 1953 by the aviator-industrialist for whom it is named, HHMI has an endowment of approximately $12.8 billion. It spent $573 million on biomedical research in 2004.

Scientists have known that an influx of calcium into a pre-synaptic cell triggers a process called exocytosis, which leads to the release of neurotransmitters. In the process, tiny bubble-like neurotransmitter-filled packages, called vesicles, move toward the pre-synaptic cell membrane, where they fuse with it, form a pore and then empty their contents into the synaptic cleft. From there, neurotransmitters diffuse to receptors on the post-synaptic cell membrane.

Chapman has spent a decade studying the biochemistry, structure and function of several proteins that promote exocytosis and fusion pore formation. The tail endings of some of these molecules ordinarily intertwine in a loose braid connected to both vesicle and membrane. In elegant experiments, Chapman’s team has shown that when one of the proteins, synaptotagmin, senses bursts of calcium, it intertwines increasingly tightly with the other molecules. This tightening is thought to pull the vesicle closer toward the pre-synaptic cell membrane.

Building on this and additional knowledge, Chapman has managed to construct in a test tube the molecular machine that allows calcium to trigger exocytosis-an ideal system for studying the process.

Toxins such as botulinum, one of the deadliest poisons known to humankind, also interact with these synaptic proteins. The poisons bind to nerve endings and prevent exocytosis, paralyzing muscles and leading to death.

Last year, Chapman’s group identified the mechanism by which botulinum enters cells. Most recently, they developed two assays that vastly improve on current technologies to detect the deadly poison.

One assay–a rapid, real-time test–could potentially be deployed to protect the food supply, soldiers on the battlefield, or used by emergency responders dealing with an unknown agent. The other, a cell-based assay, helps provide a glimpse of the toxin inside living cells. The researchers are hopeful that the test can be used to screen for millions of chemicals to see which might inhibit the paralyzing effects of the toxin.

HHMI investigators typically hold faculty appointments at universities and other research organizations. The Institute enters into long-term agreements with those institutions, and HHMI scientists conduct their research in HHMI laboratories located on the various campuses. Nearly 300 scientists already are HHMI investigators.