New gene-screen "knocks-out" pathogen targets

30 November 2009
Posted by Chris Smith.

Scientists have discovered a quick way to flush out how pathogens like bacteria and viruses target our cells.  The system could show researchers where to target their efforts in developing the next generation of antimicrobials.

DNA fragmentThe research is presented in Science by Whitehead Institute-based scientist Jan Carette and his colleagues.  The team use a human cell line called KBM7 which, unusually, contains just one copy of each chromosome (except for chromosome 8 which is present in the normal two copies).  First the researchers infect these cells with viruses which insert themselves into the cells' genetic material in random places, adding a genetic marker and simultaneously inactivating the gene into which the insertion takes place.

Next the team expose the cells to a pathogen, such as influenza. Cells that are still vulnerable to infection will succumb, leaving behind just those cells in which genes that are essential for the pathogen to gain entry or to kill the cell have been deactivated.  These genes can then be tracked down by looking for the genetic marker inserted into them previously.  The team show that the method can be used effectively to identify genes essential for influenza infectivity as well as the cellular targets of a range of bacterial toxins.

At the moment, comprehensive identifications of molecular targets are excrutiatingly difficult because scientists have to painstakingly unpick the biochemical pathways involved. With this tool, however, researchers will be able to deploy the molecular equivalent of a drag-net to find everything at once, helping them to spot new targets for rational drug design.

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