Characterising Trypanosoma tissue tropism: new perspectives for variant surface glycoproteins

ended

African trypanosomes (Trypanosoma brucei, T. congolense, and T. vivax) are extracellular parasites responsible for animal African trypanosomiasis, a livestock disease in Africa and South America that results in frequent epidemics, substantial animal mortality and economic loss. Parasites evade the host immune system through the sequential replacement of their surface coat of variant surface glycoproteins (VSGs). In T. congolense, the VSG super-family is divided into 15 phylotypes, which may have new functions beyond immune evasion. In this fellowship, we propose that VSGs may be important in tissue tropism. Despite being considered blood parasites, African trypanosomes colonise other tissues. The extent of extravascular colonisation and its impact in parasite development remain poorly understood, even though tissue distribution is linked to disease severity and may contribute to the large phenotypic variability observed in clinical cases. In this fellowship, I aim to study antigenic expression in distinct tissue reservoirs. First, I will characterise tissue tropism of T. congolense and T. vivax by comparing gene expression patterns of their extravascular populations. Subsequently, I will investigate the role of individual T. congolense VSG phylotypes in tissue colonisation and disease progression. To achieve this, I will establish Clustered regularly interspaced short palindromic repeats (CRISPR)-associated gene 9 (Cas9) genome editing technology for the first time in T. congolense. I propose a multi-disciplinary approach combining computational, cell, and molecular biology to reveal species-specific adaptions to tissues and the impact that particular VSG phylotypes may have in establishing or maintaining those niches. I will show that VSGs, well known proteins in trypanosomes, play important roles in disease that go beyond the classical antigenic variation dogma.