Structural characterisation of nutrient and innate immunity factor uptake by trypanosomes. (360G-Wellcome-102598_Z_13_Z)

Human African Trypanosomiasis is caused by the protozoan parasite Trypanosoma brucei, and is fatal if left untreated. Each trypanosome is surrounded by a surface coat of 10^8 variable surface glycoproteins (VSGs), which protect against complement-mediated lysis,and the switching of VSG expression allows evasion of the adaptive immune system. Thisproject aims to understand how the trypanosome takes up both nutrients and human immune factors in the context of the VSG coat. The project will focus on the haptoglobin-hemoglobin receptor (HpHbR), and the transferrin receptor, which allow the parasite to scavenge heme and iron respectively, in complex with human ligands. HpHbR is also involved in uptake of trypanolytic factor 1 (TLF1), a human lipoprotein particle that protects the host from numerous trypanosome species.