Researchers at the University of York have identified a protein called ESB2 that acts as a molecular shredder, enabling the African trypanosome parasite to evade the human immune system. The parasite, which causes sleeping sickness, uses ESB2 to precisely edit its genetic instructions in real time. This breakthrough solves a 40-year mystery in the parasite's biology.
The African trypanosome covers itself with a protective layer of variant surface glycoproteins, or VSG, to survive in the human bloodstream. However, it produces far more of these cloak proteins than the helper proteins encoded alongside them. Dr. Joana Faria, head of the research group at the University of York, explained that ESB2, located in the parasite's Expression Site Body, cuts apart instructions for helper genes while sparing those for the VSG cloak, as genetic instructions are processed there. The study, published in Nature Microbiology, reveals this mechanism allows the parasite to remain undetected by the host's immune system. Lianne Lansink, first author, said: 'When we first saw the molecular shredder localised in the microscope, we knew we had found something special.' Dr. Faria called it a full-circle moment, noting the puzzle had lingered since her postdoc days. The work, funded by a Sir Henry Dale Fellowship from the Wellcome Trust and Royal Society, involved researchers from the UK, Portugal, the Netherlands, Germany, Singapore, and Brazil. Sleeping sickness, transmitted by tsetse flies, can lead to confusion, disrupted sleep, and coma without treatment, affecting sub-Saharan Africa.