The complete interaction between Trypanosoma brucei and mammalian host proteins (360G-Wellcome-217138_Z_19_Z)

African trypanosomes have remarkable cell surfaces which mediate their interactions with the molecules of infected mammals. These surfaces are packed with a dense layer of the variant surface glycoprotein (VSG), allowing a population survival strategy based on antigenic variation. Within thisVSG coat operate receptors for mammalian ligands such as transferrin and haptoglobin-haemoglobin. We have shown how these receptors have evolved to bind ligands while minimising exposing of the trypanosome to the adaptive immune system. We have also shown that trypanosome receptors bind to complement components, identifying and characterising receptors for factor H and complement C3. This latter work validated a bioinformatics screen that identified a further 25 putative receptors. The aim of this proposal is to now identify the complete receptor repertoire used by Trypanosoma bruceito exploit and survive within its host. We will assess whether receptors are virulence factors and whether they represent new biology. We will understand the molecular basis for their action. We will also determine what causes the distribution and dynamics of different receptor types within the cell. This will produce detailed mechanistic insight into the cell and molecular biology of trypanosome receptors, yielding a greater understanding of both the trypanosome and the disease.