Guest Lecture: Dr. Sebastian Zoll
Dr. Zoll will give the talk, "Trypanosomes' magic bullet - Understanding the structural basis of SRA-mediated immune escape in Trypanosoma brucei rhodesiense"
Dr. Sebastian Zoll is a Postdoctoral Research Associate in the Higgins Group at the Department of Biochemistry at the University of Oxford.
Only two trypanosome subspecies are able to cause sleeping sickness in humans. To establish an infection in human blood they must overcome the innate immune system by resisting the toxic effects of the trypanolytic factors TLF1 and TLF2. These lipoprotein complexes contain an active component, apolipoprotein L1, ApoL1, a pore-forming protein that causes trypanosome cell death by a yet not well-characterised mechanism.
One of the two human infective subspecies, Trypanosoma brucei rhodesiense, differs from non-infective trypanosomes solely by presence of serum resistance-associated protein, SRA, which binds directly to ApoL1 and blocks its pore-forming capacity. Since this interaction is the single critical event that renders T. b. rhodesiense human infective, detailed structural information that allows identification of binding determinants is crucial to understand immune escape of the parasite. The structure and function analysis presented here gives molecular insight into the SRA-ApoL1 interaction, which is at the heart of human sleeping sickness and reveals adaptations in SRA that occurred as it diverged from other trypanosome surface molecules to neutralise ApoL1.