Health - Sleeping sickness tests may identify better therapies

Sleeping sickness is a formidable foe, killing thousands in Africa every year. There are only five drugs to combat the parasite, which is carried by tsetse flies, and they can have severe side effects. Worse, the parasite is becoming resistant.

"If we knew how the drugs work, we could perhaps design better ones," says David Horn of the London School of Hygiene and Tropical Medicine.

To investigate, Horn's lab exploited a phenomenon called RNA interference (RNAi) – the ability of certain small RNA molecules to block the activity of individual genes.

Horn's team used a previously created DNA library, in which the parasite's genome was cut into chunks, and these were put into bacteria in a way that generated the interfering RNAs. Each of these inactivated a parasite gene with the corresponding genetic code.

The researchers then exposed parasites to all of the interfering RNA molecules as well as each of the five drugs. If the parasites survived, it meant that the RNA sequences that had bound to them must have blocked a gene or genes needed for that drug to work. They then mapped those RNA sequences in the parasite's DNA.

Crucial genes

This revealed 55 genes that the drugs interact with – a step towards working out how they kill the parasite and finding safer drugs with the same effect.

The parasite has many genes that code for surface proteins, and Horn says he also hopes to use RNAi to probe the way the parasite turns on only one of these genes at a time. This allows it to don hundreds of new protein coats during the course of infection, so the immune system never learns to recognise it. Stopping that process might help defeat the parasite.

Journal reference: Nature, DOI: 10.1038/nature10771

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