all R. John Collier stories

Critical step traced in anthrax infection

70652986 — Mon, 26 Mar 2007 06:21:48 -0400

An anthrax bacterium secretes three nontoxic proteins that assemble into a toxic complex on the surface of the host cell to set off a chain of events leading to cell toxicity and death. Protective antigen (PA) is one of these proteins, and after binding to the cell, seven copies of it assemble into a specific complex that is capable of forming a pore in a cellular membrane. The pore permits the other two proteins to enter the cell interior, where the factors interfere with metabolic processes and can kill the infected individual.

The scientists demonstrated this role by investigating the channel's chemical make-up. Using cysteine-scanning mutagenesis, they identified the hydrophobic ("greasy") amino acid phenylalanine in protective antigen's pore-forming domain. Seven of these amino acids project into the lumen of the pore and form a collection of greasy residues, nicknamed "the phi- clamp" by the scientists. Because the water-filled lumen of the membrane pore is smaller than the folded lethal factor and edema factor, these proteins must first unfold before being actively translocated through the heptameric channel. The researchers demonstrated that the phi-clamp was critical to infection by mutating the region and blocking translocation of the toxin proteins.

R. John Collier, professor of microbiology and molecular genetics at HMS, and his colleagues found that the phi-clamp composes the main conductance-blocking site for hydrophobic drugs.

New ways found to fight anthrax

70652986 — Mon, 26 Mar 2007 05:29:06 -0400

John Collier, Presley Professor of Microbiology and Molecular Genetics at Harvard Medical School, began tinkering with anthrax molecules in 1989. He looked into a powerful electron microscope and, for the first time, saw a natural syringe made by an anthrax molecule. Seven individual proteins assemble themselves into a minute syringe that pierces human cells and injects a deadly poison. At first, the victim feels only flulike symptoms, but later, an irreversible sequence can start a person on the way to death. After isolating the syringe subunits, each composed of as many as 568 pieces, Collier and his colleagues were trying to find ways to prevent the syringe from working.

Novel anthrax treatments explored

70652986 — Mon, 26 Mar 2007 05:16:32 -0400

R. John Collier, Presley Professor of Microbiology and Molecular Genetics at Harvard Medical School, has been working on anthrax toxin for 15 years. He started his research because he found the workings of the anthrax bacterium interesting from a biological point of view. The events of the fall of 2001, when anthrax-laced letters killed several people in the United States and scared millions more, suddenly made his work of vital importance to the world. Working with several different research teams, Collier and colleagues have made several discoveries that could lead to new anti-anthrax treatments. The most interesting discovery involves the way that anthrax attacks healthy cells.

Anthrax toxin receptor discovered

70652986 — Mon, 26 Mar 2007 05:16:14 -0400

The first point of contact between anthrax toxin that invades the body and the cells that the toxin will eventually destroy is a protein, known as a "docking" protein or receptor. This docking protein was recently discovered by researchers at Harvard Medical School and the University of Wisconsin Medical School. Their discovery will, they hope, lead to a strategy for fighting anthax infection, even after symptoms have developed and treatment with antibiotics is no longer effective. The discovery was reported in Nature online on Oct. 23, 2001, and in the Nov. 8, 2001, print edition.

A strategy to neutralize anthrax toxin in the body

70652986 — Mon, 26 Mar 2007 05:16:12 -0400

A Harvard Medical School research team has developed a strategy to neutralize anthrax toxin in the body. So far they have tried the treatment in rats. Normally, rats die within hours after being injected with anthrax toxin. But when the toxin was followed minutes later with an injection of an inhibiting agent known as a polyvalent ligand -- itself completely innocuous -- the rats were protected from the toxin's effects. Asked if the polyvalent ligand can be tested in humans, research team leader R.

Anthrax immunity gene found in mice

70652986 — Mon, 26 Mar 2007 05:16:01 -0400

Anthrax is an often fatal disease that is caused by a bacterium. It has been considered a prime biological weapon in the arsenal of terrorists since attacks in the United States in October 2001 and reports elsewhere of anthrax spores being sent through the mail. Harvard Medical School researchers have identified a gene in mice that, in certain forms, renders mice resistant to anthrax. The new findings, which appeared in the October 2001 Current Biology, could aid the effort to defend humans against anthrax in two ways. First, the discoveries could shed light on what happens during the early stages of anthrax infection, and in particular how the lethal toxin released by the bug affects immune cells.

A potential new anthrax therapy

70652986 — Mon, 26 Mar 2007 05:12:49 -0400

A vaccine to protect humans against anthrax already exists, but since infection is rare, a widespread vaccination program is not practical. To be effective against anthrax, antibiotics must be given before symptoms actually develop, which is little use to those who are infected. An unvaccinated victim of anthrax usually dies within a few days. That makes anthrax contamination a deadly biological weapon. Researchers at Harvard Medical School, however, have made a discovery that makes possible a new preventive vaccine and a treatment. The method involves generating a mutation of a part of the anthrax toxin known as protective antigen.