Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod

African sleeping sickness Endemic to sub-Saharan Africa Caused by the parasite Trypanosoma brucei Transmitted by the tsetse fly Lives in the bloodstream of humans and livestock Ineffective treatments Photos: Brun et al. (2010); Prof. Michael Duszenko, Universität Tübingen

African sleeping sickness Endemic to sub-Saharan Africa Caused by the parasite Trypanosoma brucei Transmitted by the tsetse fly Lives in the bloodstream of humans and livestock Ineffective treatments Photos: Brun et al. (2010); Prof. Michael Duszenko, Universität Tübingen

How does the parasite avoid detection in our bloodstream and destruction by our immune systems?

Avoiding the immune system Immune attack 1Immune attack 2 Grey destroyed Yellow survive and multiply Yellow destroyed Red survive and multiply Process continues for many years The parasites constantly change their surface coat

How, then, can we target these parasites?

Close-up of parasite surface Parasite surface: a weak spot Known surface proteins that take up essential nutrients from the bloodstream Unknown surface proteins

Known surface proteins that take up essential nutrients from the bloodstream Unknown surface proteins Close-up of parasite surface Parasite surface: a weak spot

Aim of PhD To determine the function of these surface proteins in order to obtain a complete understanding of the molecular interaction between the parasite and the host

Identifying novel surface proteins Human and cattle bloodstreamTsetse fly Factor H

Importance of discovery Factor H-binding protein is the first discovery of a direct interaction between the host immune system and this parasite Blocking the interaction between Factor H and the parasite may prevent its survival in the host Two additional surface proteins have been discovered that bind components in the bloodstream Factor H

Commercial application Progress with company in Cambridge Producing monoclonal antibodies against two trypanosome surface proteins Could lead to a targeted treatment against African sleeping sickness

Commercial application Progress with company in Cambridge Monoclonal antibody competes/interferes with Factor H binding Parasite death Factor H

Acknowledgements Carrington Lab Members Lab FundingPhD Funding Magdalene College University of Cambridge Cambridge Society for the Application of Research