How does a trypanosome change its spots? Decrypting immune avoidance in human trypanosomes

Avoidance of host immunity is crucial for the survival of any pathogen. African trypanosomes possess a well-characterised strategy for immune evasion, termed antigenic variation. Transcriptome analysis in Trypanosoma brucei suggests antigenic variation results in huge population diversity in expressed VSG mRNA, but the predominance of post-transcriptional control of gene expression and the preponderance of VSG pseudogenes means it remains questionable whether the abundance and diversity of VSG mRNAs is reflected in the surface (glyco)proteome. In the related kinetoplastid parasites T. cruzi and Leishmania, strategies for immune evasion are much less clearly understood and any link between genomic, transcriptomic and surface proteome variation due to immune pressure has not been examined. The development of methodologies to characterize the surface proteome of kinetoplastid parasites are therefore paramount and will provide transformative understanding not merely of immune evasion, but potentially other phenomena fundamental to aspects of parasite biology and control, such as host cell entry and passage through the lifecycle. We aim to use established high throughput microfluidic proteomic and next generation sequencing approaches to quantify the correspondence between surface proteome and transcriptome diversity, as well as link this diversity to underlying genome changes. We will examine this question in each kinetoplastid parasite before and after exposure to host immunity to inform our understanding of mechanisms of immune escape and ultimately vaccine design.