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ScienceWise - Jul/Aug 2009

Sleep No More

Article Illustration
Image: Dean, S., Marchetti, R., Kirk, K. and Keith R. Matthews (2009) “A surface transporter family conveys the trypanosome differentiation signal” Nature 459(213-217).

A Discovery that Could Open up Doors to Prevent Sleeping Sickness

Sleeping sickness continues to be a worrying disease in many regions of the world.  Having a probable history of thousands of years, it still affects 50,000 to 70,000 people in sub-Saharan Africa, with an estimated 30,000 new victims each year. Scientists have worked to come up with cures, though few have been successful. The low success rate could be due to the lack of a full understanding of its causative parasite Trypanosoma brucei. However, hope has resurfaced from the results of research in recent years, including a ground breaking discovery resulting from a collaborative study between the University of Edinburgh and the Australian National University. 

Having made contact with each other in a conference, Professor Keith Matthews of the University of Edinburgh and Professor Kiaran Kirk of the Australian National University, together with their research students Sam Dean and Rosa Marchetti (respectively) dedicated themselves to study the proteins and signals that enable the parasite to undergo its various transmission stages. The research has resulted in the discovery of PAD (proteins associated with differentiation), and that PAD is crucial for the transmission of Tryponosoma brucei from its “stumpy-form” to its procyclic form.  The encouraging part lies in the fact that without PAD Tryponosoma brucei will not be able to transmit into the procyclic stage to proliferate in the tsetse fly and therefore cannot be transmitted to humans.

“It is an important first step that we have made, and we hope that with this piece of puzzle, we can now engage in the process of gaining a better picture of the parasite”, Rosa Marchetti said.

Trypanosoma brucei, the “sleeping sickness” parasite, is a polymorphic single celled organism that can shift its shape from a long, slender form with a flagellum – “a tail” – to a short stumpy structure with no flagellum.  The parasite depends on tsetse flies as a means of transmission, and exists in the “stumpy-form” when sucked up by the flies. When the infected Tsetse flies proceed to bite other hosts, they release T. brucei into the victim. T. brucei then shifts to its slender flagellated forms and proliferates in the blood and lymph. As the trypanosome invades the central nervous system, it sets off the chronic infection stage when the victim suffers from increasing apathy, mental dullness, paralysis or convulsions and ultimately, death.

The fight against sleeping sickness has spanned many decades. Some drugs have proved effective, though they come with damaging side effects, and the parasite has started to build up its resistance to them. As a full understanding of the parasite has not yet been achieved, there are no vaccines, and it is difficult to treat the sickness as the symptoms often occur in many other conditions.

It is hoped that this latest discovery could begin a new era for research on trypanosomes. Until now it was known that the parasite could not proliferate in its “stumpy-form” until it shifted to the procyclic form, but its intermediate mechanism was unclear. However, now that this study equips us with the knowledge of proteins (PAD) responsible for the transmission to its procyclic form, there is potential for therapeutic agents to be produced. Should the therapy work in keeping the parasite in its “stumpy-form”, it would prevent the transmission of the parasite to humans.

This collaboration has proved to be a rewarding experience for our ANU researchers – apart from the discovery, it was a thoroughly refreshing journey for Professor Kirk and Rosa, who both specialise on Plasmodium – the Malaria parasite.
Rosa appreciated the opportunity, “It was a change to be able to study another parasite. I think that Trypanosomes don’t get the same attention as Plasmodium because the sleeping sickness isn’t as common as Malaria. Thus this collaboration allowed us to contribute to helping with understanding this fascinating parasite.”

Both teams maintained communication via emails and web conferences, and the collaboration experience was further enhanced by a visit from Sam to Professor Kirk’s laboratory, having obtained a grant by the Journal of Cell Science. It was then that Rosa was able to practice her scientific communication skills.

“Apart from the research context, the lesson that I gained was on how to work with someone who is from an entirely different laboratory and would have different ways of doing things. I had to guide Sam on our procedures, and it proved to be a great teaching experience. The key for me was to have a firm idea of why we do what we do, so we can pass on a clear message to the others.”

Both groups are excited with the findings, and further collaborations have been discussed. More work needs to be done, but in the meantime we can be positive about one thing: There is a hope.

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