A SYSTEMATIC APPROACH TOWARDS UNDERSTANDING INNATE IMMUNITY AGAINST TRYPANOSOMES. (360G-Wellcome-085481_Z_08_Z)

The project aims to provide a cellular and molecular view of innate immunity against trypanosomes. Despite recent findings a detailed structural explanation of the events occurring at the molecular and cellular level is missing. Specifically, inter-related and complementary aims are to: (1) Follow the morphologically distinct stages from uptake of the lytic factor to trypanosome cell death by generating cryo-electron tomograms, i.e. high-resolution 3-dimensional descriptions of organelle architecture and arrangement under native conditions. (2) Generate the first 3-dimensional description of this endocytic pathway under native conditions. (3) Investigate the molecular architecture of APOL1 and SRA, the molecular nature of their interaction and the structural changes that APOL1 undergoes upon integration into the lysosomal membrane. For this I will also initiate structural studies on the whole APOL family, complementing functional work on these proteins conducted in the laboratory of Professor Etienne Pays. The structural and biophysical studies will be in direct relation to functional work conducted in the laboratories of Professor Pays and Professor Keith Gull.