No vaccine exists for human African trypanosomiasis (sleeping sickness), and few drugs are available. But the recent publication of the genome sequence for Trypanosoma brucei, the parasite responsible, has increased our understanding of the parasite's biology and has boosted the search for drug targets.

One promising target is the flagellum – the 'tail' that propels the parasite through the bloodstream. Professor Keith Gull at the University of Oxford and colleagues have shown that the flagellum plays a critical role in cell division and is, therefore, essential for parasite survival. They have identified flagellar proteins that, being unique to the trypanosome, have potential as drug targets.

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Other studies have revealed further chinks in the trypanosome's armour. Trypanosomes use an unusual mechanism to regulate gene activity, in which messenger RNAs are held by RNA-binding proteins until they are needed. By interfering with this system, Dr Ed Hendriks and Dr Keith Matthews were able to alter a specific step in differentiation – the first time this process has been genetically modified in trypanosomes.

Exploiting a naturally occurring parasite transporter, Professor Ian Gilbert and colleagues showed that nitroheterocycle compounds attached to melamine were effective against the parasites that give rise to human African trypanosomiasis.

Lastly, Professor Alan Fairlamb, whose Wellcome Trust Principal Research Fellowship was renewed this year, is searching for candidate molecules to screen in a dedicated drug discovery programme at the University of Dundee. He and his team are focusing their search on a molecule called trypanothione – unique to trypanosomes and Leishmania parasites – and its associated enzymes.

Image: A malformed trypanosome after cell division has been disrupted; Helen Farr and Keith Gull

External links

• Broadhead R et al. Flagellar motility is required for the viability of the bloodstream trypanosome. Nature 2006;440(7081):224–7.
• Hendriks EF, Matthews KR. Disruption of the developmental programme of Trypanosoma brucei by genetic ablation of TbZFP1, a differentiation-enriched CCCH protein. Mol Microbiol 2005;57(3):706–16.
• Baliani A et al. Design and synthesis of a series of melamine-based nitroheterocycles with activity against Trypanosomatid parasites. J Med Chem 2005;48(17):5570–9.
• University of Dundee Tropical Disease Initiative