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Anthrax Researcher Collier To Give Kinyoun Lecture, Oct. 7

By Jeff Minerd

Dr. R. John Collier, a leading expert on anthrax toxin and other bacterial toxins, will deliver this year's Kinyoun Lecture, sponsored by the National Institute of Allergy and Infectious Diseases. His talk, titled "Anthrax Toxin: Structure, Activity, and New Inhibitors," will take place on Monday, Oct. 7 at 9 a.m. in Lipsett Amphitheater, Bldg. 10.

Collier, the Maude and Lillian Presley professor of microbiology and molecular genetics at Harvard Medical School, has dedicated his distinguished career to understanding how bacteria cause disease. He elucidated the molecular structure and activity of many important bacterial toxins and has applied this knowledge to create new strategies for treating and preventing bacterial illness.

Dr. R. John Collier
Early in his career, Collier discovered that diphtheria toxin crosses the cell membrane and directly inactivates a cellular protein called elongation factor-2, thereby hindering the cell from making new proteins. This research was the first to show that a bacterial protein toxin could breach the protective mammalian cell membrane. His finding was crucial to later discoveries that many major toxins — including cholera, pertussis, tetanus, botulinum and anthrax toxins — enter mammalian cells and target particular molecules within them.

In recent years, he has focused his research on understanding how such intracellular toxins invade cells. His studies have revealed two distinctly different types of molecular machinery that toxins use to penetrate membranes, one employed by the diphtheria toxin, the other by the anthrax toxin.

In the case of anthrax toxin, Collier's research has proved timely. Well before September of last year, he and his coworkers developed novel strategies to block anthrax toxin, based on new information about its structure and activity. One strategy introduces mutations in the subunit of the toxin that forms an entryway, or pore, in the cell membrane. These mutations convert the pore-forming subunit into a potent "dominant negative inhibitor" (DNI) of toxin action. The DNI combines with normal pore-forming subunits produced during anthrax infections and renders it inactive, ultimately blocking entry of the toxin into cells.

In a second strategy, working with Dr. John Young of the University of Wisconsin, Collier identified the long-elusive anthrax toxin receptor, or ATR, on the surface of animal cells. ATR is the molecule the toxin uses to gain cell entry. The researchers then found the specific region of ATR where the toxin binds. With this information, they produced a "decoy" molecule to divert the anthrax toxin — a shortened, free-floating version of the receptor that binds to the toxin before it attaches to cells.

In the laboratory, the DNI and decoy molecules completely protected animal cells from the toxin. These two toxin inhibitors, plus a third one developed by Collier and colleagues, will soon be tested in animal models as potential anthrax therapies.

Collier holds a B.A. from Rice University (1959) and a Ph.D. from Harvard (1964), both in biology. After postdoctoral study at the University of Geneva, he joined the faculty of the department of microbiology (then called bacteriology) at the University of California at Los Angeles. In 1984, he moved to Harvard, where he served 6 years as graduate dean, followed by a year as acting chair of the department of microbiology and molecular genetics.

Collier received the Eli Lilly Award in Microbiology and Immunology in 1972, the Paul Ehrlich Prize in 1990, and the Selman Waksman Award in 1999. He was elected to the National Academy of Sciences in 1991. Since 1967, his research has been supported primarily by NIAID.

The Kinyoun Lecture honors Dr. Joseph Kinyoun, who, in 1887, founded the Laboratory of Hygiene from which NIH evolved. The lecture highlights research advances in the understanding of infection and immunity. All are invited to a reception in the Lipsett lobby after the talk.

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