To survive in the human bloodstream, African trypanosome parasites coat themselves with a protective layer made of a protein called variant surface glycoprotein (VSG). Research published in natural microbiology have now identified a key protein that allows the parasite to precisely control this protective ‘mantle’.
Researchers discovered that a newly identified protein, ESB2, plays a key role in this process. It acts as a “molecular shredder”, allowing the parasite to remain hidden by cutting off selected parts of its genetic instructions as it is generated.
Understanding this highly precise mechanism allows scientists to gain new insights into weaknesses in the parasite’s life cycle. This could ultimately lead to improved treatments for sleeping sickness, which remains a major problem across sub-Saharan Africa.
Sleeping sickness is transmitted through the bite of the tsetse fly. Without treatment, the parasite can invade the central nervous system and cause severe symptoms, including disturbed sleep patterns, confusion, and coma.
“Molecular shredder” that edits genetic instructions in real time
Dr Joanna Faria, senior author of the study and head of the research group at the University of York, explained: “We found that the secret to the parasite’s ability to remain invisible lies not in what it prints, but in what it chooses to edit. By placing a ‘molecular shredder’ directly inside the ‘protein factory’, the parasite is able to edit its genetic manual in real time.”
“This suggests a fundamental shift in the way we think about infection. The survival of many organisms may depend less on how they issue their genetic instructions and more on how they are destroyed at the source.”
Solving a 40-year-old mystery of gene expression
The discovery helps explain a long-standing mystery in the parasite’s biology that has puzzled scientists for decades. The genetic instructions that create the parasite’s protective “mantle” also include several “helper genes” that support survival and immune evasion. Based on this setup, the scientists expected the parasites to produce similar amounts of each protein.
Instead, the parasite produces large amounts of cloak proteins but only small amounts of helper proteins. New findings reveal that this imbalance is no coincidence.
By identifying ESB2, the research team showed that the parasite does not simply control gene production, but rather regulates gene production by disrupting specific instructions.
Precise control inside the expression site body
ESB2 is located within the parasite’s protein production center known as the expression cytobody. When genetic instructions are processed, ESB2 acts like a “molecular blade”, instantly cutting through the helper gene section, but leaving the cloak-related instructions intact.
This real-time editing allows the parasite to produce exactly what it needs to avoid detection by the host’s immune system.
Breakthrough results from a research team at the University of York
The discovery is the first major result from Dr Faria’s new laboratory at the University of York and contributes to the city’s growing reputation as a center for life sciences research.
The project was funded by the Sir Henry Dale Fellowship, a partnership between the Wellcome Trust and the Royal Society, and brought together researchers from the UK, Portugal, the Netherlands, Germany, Singapore and Brazil.
“When we first saw the molecular shredder being located in the microscope, we knew we had discovered something special,” said Leanne Lansink, lead author of the study.
Dr Faria added: “This discovery is a true full-circle moment for me. The mystery of how this parasite manages the asymmetric expression of its genetic manual has been a cold case that has been at the back of my mind since my postdoctoral years. “It’s incredibly rewarding to finally be able to solve it now, as the lab’s first major result. It’s a testament to what a fresh lab and a diverse group of scientists can accomplish when they look at an old problem from a completely new perspective.”
