Challenging trypanosome antigenic variation paradigms using natural systems

Several pathogens avoid host immunity by periodically changing the proteins they express on their surface – a phenomenon called antigenic variation (AV). An extreme form of AV is exhibited by African trypanosomes, which cause human disease, although their greatest impact is through causing disease in livestock which significantly limits economic prosperity in sub-Saharan Africa. The molecular mechanisms of antigen switching in trypanosomes have been extensively studied over the past three decades providing a classic model for AV. However, several key components of this model have been challenged through recent discoveries. This includes a new appreciation of the importance of gene mosaics in generating new variants, as well as the contributions of parasite development and body compartmentation to the infection dynamic. It has become clear that the existing infection model – Trypanosoma brucei in mice – poorly reflects the dominant infections found in livestock – T. congolense and T. vivax.

We will systemically compare the contributors to AV in different trypanosome species and hosts and analyse the effects of perturbing key molecular regulators. The outputs will be integrated into a mathematical framework to highlight important parameters in the infection dynamic.

Our research findings could be used to help combat the parasite.