Structural and functional dissection of the molecular machinery responsible for singular antigen expression and immune evasion in African trypanosomes

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In the host-pathogen arms race, antigenic variation is one of the most sophisticated virulence mechanisms. Some of the deadliest parasites, like African trypanosomes and malaria parasites, are able to systematically alter the identity of proteins displayed to the host immune system, causing high mortality and morbidity among the world's poorest populations. Trypanosomes are masters of disguise, expressing their variant-surface-glycoprotein in a monogenic fashion from thousands of possible genes - a fine example of extreme biology and a great model system. The pursuit for the machinery responsible for singular-antigen-expression has been a 50-year long quest and had remained elusive in every organism. Its recent identification in trypanosomes ((PMID: 31289266; 33432154) represents a timely opportunity to crack this long-standing mystery. This project aims to:-purify this novel protein complex and solve its tridimensional structure by cryoEM, which will be critical to understand its mechanism of action.-identify key post-translational modifications and characterise their functional/regulatory role. Therefore, the successful applicant will be trained on several cutting-edge technologies, including gene editing (CRISPR/Cas9), mass-spectrometry, next-generation sequencing, protein purification in native conditions and cryoEM. Notably, understanding the molecular mechanisms underpinning antigenic variation is invaluable, as it greatly challenges vaccine development against several organisms.