Bulletin

Issue: January/February 2004

Research in Action

Combating anthrax as a weapon of terror

'We could imagine sampling the air around major events that may be targets for bio-terrorists by using a peptide to sense the presence of these spores. Ultimately the test should be simple and cheap - a bit like a pregnancy test.'

La Trobe University scientists are using their own unique peptide 'library' containing a thousand million molecular sequences in a project aimed at eliminating anthrax as a potential weapon for terrorists.

The 'library' should enable them to identify molecules which potentially can be used in two ways. One is to prevent the spread of anthrax by detecting the presence of its spores before they enter a human. The other is to stop anthrax carrying out its often fatal work after infection.

One molecule they have found, code named T1, has the right characteristics. It will hopefully eliminate the aspect that makes anthrax so deadly once it enters the human body. This is the fact that by the time the disease is diagnosed as anthrax - rather than the common cold or other viral infections which have similar symptoms in their early stages - it is usually too late to save the victim's life.

Even though infection caused by anthrax spores may do little harm initially, by the time symptoms are diagnosed, they have already produced the deadly anthrax toxin which kills cells in the immune system.

The research aims to identify and put to use a suitable molecule which will prevent the active part of the toxin from causing this carnage within human cells.

The La Trobe team, headed by molecular biologist Dr Mick Foley, is working with researchers at the Defence Science & Technology Organisation (DSTO), CSIRO and the project is being carried out within the national Cooperative Research Centre for Diagnostics, of which La Trobe is a member.

A 'library' of one thousand million molecular sequences, developed to assist malaria glandular fever research by La Trobe University senior researcher, Drs Joanne Casey and Andy Coley, has become the vital tool in the anthrax research.

Joint La Trobe and DSTO doctoral student, Mr Ross Weston - working with his La Trobe supervisor, Dr Foley and DSTO colleague Dr Malcolm Alderton - says that Bacillus anthracis, which causes anthrax, was one of the most potent and potentially damaging biological warfare agents.

Toxins are often found in fatal concentrations before diagnosis, and currently there are no therapeutics against the toxin. One of three proteins which comprise the toxin, LF (lethal factor) is the problem. After an anthrax spore enters the body, LF can bind to cells of different parts of the body, including the skin, lungs or intestines via a 'receptor' - a protein on the surface of a cell that usually binds to some normal protein in the body. Once inside, it acts like a pair of molecular shears, cutting an important protein, causing the cells to crash.

This is where the 'peptide collection' comes into operation. Called a 'phage display library', it is a collection of peptides housed on the surface of bacteriophage - a virus that infects bacteria. A whole library can fit in a single drop of water, which can be 'panned' to find 'ligands', molecules that display an affinity with another molecule by attaching itself to it.

Dr Foley says the system enables the researchers to pass millions of molecules over a desired target like, for example, the anthrax toxin LF to find any that might bind tightly to it. By this method Mr Weston found that T1 binds to LF.

'Indeed T1 seems to bind to the business end of the toxin - the so-called 'active site' that the toxin uses to slice its protein target - suggesting that it might be a useful compound in the search for an anthrax therapy. Work continues to find other ligands as each has different characteristics that might be of value.

'We now need to work with T1 and any other suitable peptides we can find to ascertain whether we can use them to develop both a diagnostic device or ?screen? to detect the presence of anthrax spores, and a therapeutic drug which can be administered immediately somebody displays anthrax symptoms to stop the toxin from doing its is work. This would be a very cheap drug as the T1 peptide can be easily and economically synthesised.'

Dr Foley explains that the T1 peptide, or molecules derived from it, would bind to the anthrax toxin and act like a 'spanner in the works' protecting cells that would normally be killed.

'Other peptides that bind to anthrax spores could be used to detect spores in air or in suspicious letters, as happened in the US in September 2001.

'We could imagine, for example, sampling the air around major sporting events that may be targets for bio-terrorists, like the Olympics, and using a peptide to sense the presence of these spores.

'The test could give a colour signal if spores are detected and no colour if they are absent. Ultimately the test should be simple and cheap - a bit like a pregnancy test.'

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