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African Trypanosomes Use a Molecular Shredder to Avoid Detection in the Bloodstream
In mammalian hosts, the African trypanosome parasite replicates freely in the bloodstream, despite being fully exposed to the immune system. To do this, the pathogen relies on the stochastic switching of a Variant Surface Glycoprotein (VSG) for immune evasion.
Now, a study presents the newly discovered ESB2 protein—an active RNA endonuclease—which acts as a “molecular shredder,” allowing the parasite to avoid detection by fine-tuning expression of virulence genes through specialized RNA decay.
Transmitted by the bite of the tsetse fly, if left untreated, the parasites invade the central nervous system, causing neurological issues including severe sleep disruptions, confusion, and coma. This understanding of a previously undescribed mechanism of how the parasite avoids detection with incredible precision may allow researchers to identify new vulnerabilities in its life cycle. It may open the door for future treatments for sleeping sickness—a disease that continues to have a devastating impact on communities across sub-Saharan Africa.
This work is published in Nature Microbiology in the paper, “Specialized RNA decay fine-tunes monogenic antigen expression in Trypanosoma brucei.”
“We’ve discovered that the parasite’s secret to staying invisible isn’t just what it prints, but what it chooses to redact,” noted Joana Faria, PhD, leader of the research group at the University of York. “By placing a ‘molecular shredder’ directly inside its ‘protein factory,’ the parasite can edit its genetic manual in real-time. This suggests a fundamental shift in how we view infection: survival for many organisms may depend less on how they issue genetic instructions and more on how they destroy them at the source.”
The discovery provides an answer to a lingering question in the parasite’s biology that has challenged scientists for 40 years. The genetic manual for the VSG also contains several genes needed for survival and immune evasion. Logic suggests that when the parasite follows these genetic instructions, it should produce equal amounts of each protein. However, the parasite somehow produces a mountain of cloak proteins but only a tiny amount of helper proteins.
By identifying the ESB2 protein, the York team discovered that the parasite controls its genetic messages through destruction rather than just production. ESB2 sits directly inside the parasite’s protein factory, known as the Expression Site Body (ESB). ESB2 acts as a “molecular blade,” ensuring the parasite expresses exactly what it needs to remain hidden from the host’s immune system.
The researchers applied TurboID-mediated proximity labelling mass spectrometry (PL-MS) to “map the ESB post-transcriptional network, identifying three new components: ESB-
associated protein 1 (ESAP1) and ESB-specific proteins 2 and 3 (ESB2 and 3).” They then characterized ESB2 as an RNA endonuclease that negatively regulates ESAG transcripts.
Crucially, they write, they demonstrate that “ESB2 recruitment depends on both its own catalytic activity and a hierarchy involving VEX2, ESAP1, and ESB3.”
“This discovery is a real full-circle moment for me,” added Faria. “The mystery of how this parasite manages the asymmetric expression of its genetic manual has been a cold case in the back of my mind since my days as a postdoc. To finally solve it now, as the first major output of my own lab here at York, is incredibly rewarding. It’s a testament to what a fresh lab and a diverse group of scientists can achieve when they look at an old problem from a completely new angle.”
The post African Trypanosomes Use a Molecular Shredder to Avoid Detection in the Bloodstream appeared first on GEN – Genetic Engineering and Biotechnology News.
You know when you are at the eye doctor getting an updated prescription, and suddenly the world snaps into sharper focus? Physicists at the University of California (UC), Berkeley, have now done something similar for electron microscopy. By introducing phase contrast into a cryo‑electron microscope, they have delivered dramatically sharper images of some of biology’s smallest and most elusive proteins.
The advance comes from a new laser phase plate (LPP), described in the paper “Laser phase plate improves structure determination of small proteins by cryo‑EM,” which was published recently in Science. Led by physicist Holger Mueller, PhD, of UC Berkeley and Lawrence Berkeley National Laboratory, the team demonstrated that a laser‑driven phase plate can overcome one of cryo‑EM’s most persistent limitations: poor contrast for small proteins.
Cryo‑EM has transformed structural biology over the past decade, earning a Nobel Prize in 2017 for enabling high‑resolution structures without crystallization. But despite its impact, the technique still struggles with proteins below ~70 kilodaltons—a size range that includes about 90% of the human proteome. “Because of signal-to-noise limitations, the majority of human and animal proteins are too small to be analyzed by these methods [cryo-EM and cryoelectron tomography]. The increase in signal-to-noise ratio provided by this laser phase plate is expected to overcome these important limitations.”
The new LPP begins to address that problem. The LPP uses an intense, continuous‑wave laser to shift the phase of the electron beam itself. This produces true phase contrast without dimming or destabilizing the beam. Mueller described the laser focus as “75 kilowatts focused to a few microns… That’s more powerful than what you use for welding. It has more power than a military laser. It builds up the brightest continuous laser focus ever.”
Installed in a custom Thermo Fisher Titan Krios, the LPP immediately improved the clarity and resolvability of small proteins, including hemoglobin, which sits at the lower limit of what today’s cryo‑EM instruments can handle. As the authors wrote in the abstract: “Here, we show that the laser phase plate (LPP)… enhances the resolution in single-particle reconstruction of small proteins by improving specimen-motion correction, recovery of information from the early frames, as well as particle visualization, 3D classification, and alignment.”
These improvements were achieved using standard defocus ranges and reconstruction workflows. “For the most challenging cases—small particles, bad specimens—the laser produces a very considerable advantage,” Mueller said.
The impact extends beyond single‑particle analysis. Cryo‑electron tomography (cryo‑ET), which assembles multiple angular views of a molecule or protein into a three-dimensional image, stands to benefit even more. “With cryo-ET, we’re looking at small, very complicated cellular material that’s incredibly crowded inside the cell,” said Bridget Carragher, PhD, founding technical director of imaging at Biohub. “It’s like a forest of trees, and you’re trying to find one leaf on one tree in there. Cryo-ET needs a dramatic step forward in contrast, so we can start to see what’s going on inside the cell. That’s what the laser phase plate promises to give us.”
Biohub is developing a dual‑laser version of the system, designed to reduce component wear and minimize aberrations. Meanwhile, Mueller’s team is pushing toward imaging proteins as small as 17 kilodaltons, a threshold that would open access to vast regions of the human proteome previously invisible to cryo‑EM.
“This technology is a step function change for biology,” said Stephani Otte, PhD, Biohub’s vice president of imaging science. “What was once invisible will become visible—and that changes everything about how we understand disease.”
“The bottom line is, if you have a large protein and a really good sample—a fresh one or one frozen without bubbles, for example—you may not need the phase plate to get a single, high-quality image. But for a small protein and a bad sample, laser-on is best,” Mueller said. “This could fill an enormous gap in our knowledge of protein structures that can’t be crystallized or are too small for today’s cryo-EM. And it will be revolutionary for cryo-ET.”
The post Laser‑Driven Phase Contrast Enhances Cryo‑EM Resolution of Small Proteins appeared first on GEN – Genetic Engineering and Biotechnology News.
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STAT+: Updated: Tracking RFK Jr.’s promises to remake health in America
Updated June 11, 2026
WASHINGTON — A pledge to “Make America Healthy Again” earned Robert F. Kennedy Jr. his job atop U.S. health agencies a year and some change ago. He’s now had the opportunity to turn his words into action, with mixed results.
“All one needs” to prove the health secretary’s attentiveness is to “review my unprecedented list of accomplishments on a wide range of issues, all of which I drove,” Kennedy posted on X on Wednesday in response to a journalist.
Updated June 11, 2026
WASHINGTON — A pledge to “Make America Healthy Again” earned Robert F. Kennedy Jr. his job atop U.S. health agencies a year and some change ago. He’s now had the opportunity to turn his words into action, with mixed results.
“All one needs” to prove the health secretary’s attentiveness is to “review my unprecedented list of accomplishments on a wide range of issues, all of which I drove,” Kennedy posted on X on Wednesday in response to a journalist.
Can any of the new obesity medications in development stand out from the pack? Which company just broke records with its IPO? And will the Food and Drug Administration allow greater access to experimental peptides?
We discuss all that and more on this week’s episode of “The Readout LOUD,” STAT’s biotech podcast.
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