To survive in the human bloodstream, African trypanosome parasites wear a “cloak” made of a protein known as variant surface glycoprotein (VSG). This research natural microbiologyidentify proteins that allow the parasite to fine-tune this “mantle.”
The newly discovered ESB2 protein acts as a ‘molecular shredder’, allowing parasites to evade detection by destroying specific parts of their genetic instructions with surgical precision during production.
Understanding how the parasite does this with such precision has allowed researchers to identify new vulnerabilities in its life cycle. This opens the door to future treatments for sleeping sickness, which continues to have a devastating impact on communities in sub-Saharan Africa.
Infected by a tsetse fly bite and left untreated, the parasite invades the central nervous system and causes neurological problems, including severe sleep disturbances, confusion, and coma.
We discovered that the secret to keeping parasites invisible is not just what you print, but what you choose and edit. By installing a “molecular shredder” directly inside a “protein factory,” the parasite can edit its genetic manual in real time.
This signals a fundamental shift in the way we view infections. The survival of many organisms may depend less on how they issue their genetic instructions than on how they are destroyed at their source. ”
Dr Joanna Faria, senior author of the study and leader of the University of York research group
The discovery provides an answer to a strange quirk in the parasite’s biology that has puzzled scientists for 40 years. The “cloak” genetic manual also includes several “helper genes” necessary for survival and immune evasion. Logic suggests that if the parasite follows these genetic instructions, it should produce the same amount of each protein. However, the parasite somehow produces large amounts of the mantle protein, but only small amounts of the helper protein.
By identifying the ESB2 protein, the York team discovered that this parasite controls its genetic messages through destruction as well as production.
ESB2 is located directly inside the parasite’s protein factory known as the expression cytobody. While the genetic manual is being printed, the ESB2 acts as a “molecular blade”, instantly shredding the helper section while leaving the cloak’s instructions intact. This real-time editing ensures that the parasite expresses exactly what it needs to keep hidden from the host’s immune system.
This breakthrough is the first major result of Dr Faria’s new laboratory at the University of York and signifies the city’s growing reputation as a global hub for life sciences.
The project was funded by the Sir Henry Dale Fellowship, a partnership between the Wellcome Trust and the Royal Society, bringing together expertise 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 achievement. It’s proof of what a fresh lab and a diverse group of scientists can accomplish when they look at an old problem from a completely new perspective.”
sauce:
Reference magazines:
run sink, rim, Others. (2026). Specialized RNA degradation fine-tunes the expression of single-gene antigens in trypanosomes brucei. natural microbiology. DOI: 10.1038/s41564-026-02289-4. https://www.nature.com/articles/s41564-026-02289-4
