Research: Trypanosome flagellum analysis provides new targets for therapies

14 March 2006

An analysis of key proteins in the trypanosome flagellum has identified numerous new targets for therapeutic intervention.

Trypanosoma brucei is a unicellular parasite endemic in sub-Saharan Africa. It causes African sleeping sickness in humans and a deadly wasting disease in cattle. There is no vaccine and few effective drugs.

To move around, trypanosomes depend on a specialised flagellum. With colleagues in Manchester and Lancaster, Professor Keith Gull, a Wellcome Principal Research Fellow at the University of Oxford, carried out a proteomic analysis of the flagellum – identifying all proteins involved in its construction and operation. Using RNA interference, they then systematically eliminated each protein in turn and assessed the impact on the flagellum and the organism more generally.

They discovered that knocking out flagellum function disrupted cell division in human bloodstream forms of the parasite, suggesting new options for targeting the parasite. In addition, they compared the make-up of the trypanosome flagellum with those of other organisms, including humans, identifying trypanosome-specific flagellar proteins that are also potential drug targets.

External links

• Broadhead R et al. Flagellar motility is required for the viability of the bloodstream trypanosome. Nature 2006;440(7081):224–7.