Wellcome Centre for Integrative Parasitology

The parasites that cause African sleeping sickness are masters of disguise. They can hide from our immune system by replacing the proteins on their surface, constantly changing to avoid being recognised and destroyed. This process (a phenomenon known as antigenic variation or AV) has been studied by scientists for over forty years and its molecular details are well known, at least for one species of the parasite, Trypanosoma brucei. However, this is not the most important trypanosome species in sub Saharan Africa, and most of our knowledge is based on laboratory studies that may not well represent how the parasite operates in the real-world.

Now, a team of scientists, including researchers from the WCMP, has been awarded over £2 million by the Wellcome Trust to find out how the most prevalent trypanosomes, Trypanosoma congolense and Trypanosoma vivax, establish infections and survive in animals, where they cause enormous economic hardship through a livestock disease in Africa called ‘nagana’. This name is derived from the Zulu word for ‘useless’, highlighting the devastating impact the parasite has on afflicted cattle. The teams, based in Edinburgh, Glasgow, Liverpool, Lisbon, Heidelberg and Baltimore, will pool their expertise to compare human and livestock parasites and discover how they establish long term infections through immune evasion and maximise their chances of spread.

This new research will systemically compare AV in different trypanosome species and hosts, and analyse the effects of key molecular regulators. The outputs will be integrated into a mathematical framework to highlight important parameters in the infection dynamic, information that we anticipate could be exploited to help combat the parasite and may be relevant for other pathogens that use AV for survival. 

Lead researcher, Professor Keith Matthews, based at the University of Edinburgh, says “We think these important livestock trypanosomes are doing things very differently. Our collaboration has the possibility to identify vulnerable points in the parasite’s defences that could be targeted using drug therapy or even vaccines – something previously considered impossible. The consequences for economic improvement in sub Saharan Africa could be enormous.’

The WCMP's Dr Richard McCulloch says ‘Since the first descriptions of how trypanosomes switch their surface proteins, a huge range of genetic tools have been developed in Trypanosoma brucei, revealing how gene rearrangements and expression changes direct immune evasion. However, most of these studies have been in cell culture and recent work, including in Glasgow by Dave Barry, who until recently directed WCMP, has raised important questions about how surface protein changes operate in long term infections and contribute to parasite host-to-host transmission. In addition, we have limited genetic understanding of immune evasion by nagana-causing trypanosomes. By deploying genome-wide genetic approaches, underpinned by mathematical modelling directed by Dr Christina Cobbold at the University of Glasgow, we will address these large-scale questions of a crucial host-parasite interaction’.

 

 

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First published: 5 September 2017