Sifting Through A Molecular Bin
Sifting through a molecular bin
When a mammalian cell is faced with a nasty or dangerous molecule, it often sends it to the “bin”: a section in the cell called the lysosome where molecules get smashed up and recycled.
But some toxins seem to get around this security measure, and a project at University College Dublin is looking to figure out why. The hope is that what they identify could help find new ways to deliver therapeutic drugs or nanoparticles into cells more effectively.
When a mammalian cell is faced with a nasty or dangerous molecule, it often sends it to the “bin”: a section in the cell called the lysosome where molecules get smashed up and recycled.
Dangerous molecules, such as ricin (a poison that was infamously injected into Georgi Ivanov Markov from an umbrella tip) and the agents in the bacteria Shigella and E coli that give us food poisoning, have ways to avoid that route to the cellular bin, says Jeremy Simpson, professor of cell biology at the SUCD. Instead, they seem to get moved into cells in a way that means they can remain active.
“The premise we are working on is that if we could understand how these toxins traffic through these pathways, then we could apply this knowledge in the drug delivery context,” says Simpson.
Plans are underway to individually knock down around 22,000 genes in human cells growing in the lab, and use an automated system to look at what subsequently happens when a safe version of an E coli toxin or else artificial nanoparticles are trafficked into cells.
“We will do all all 22,000 genes systematically,” says Prof Simpson. “Once we have got a list of genes associated with these pathways we can hopefully be a bit more intelligent about understanding which genes and proteins are responsible for how these things go inside cells. And the main driver for what we would like to do, is to use this knowledge to improve drug delivery.”
Image: Montage showing one of the toxins used at different points after internalisation into cells. In these images you can see how the toxin changes its distribution in the cell over time.
This is part of an article which was published in the Irish Times, Science Today, 23/02/12