The Parasite’s Weakest Link

A New Weak Spot in a Deadly Disease

Wake up—literally. A groundbreaking discovery about a long RNA molecule may offer new hope in the fight against sleeping sickness, a fatal disease caused by a single-celled parasite. The molecule, identified as crucial to the parasite's development inside the tsetse fly, could disrupt the transmission chain to humans and other mammals.

A research team led by Prof. Shulamit Michaeli of Bar-Ilan University's Faculty of Life Sciences, has discovered that interfering with the molecule’s function halts the parasite’s growth inside the tsetse fly, effectively blocking its ability to infect. Michaeli, who has spent years studying this family of parasites, hopes the new finding could lead to a future treatment.

A Threat That Crosses Continents

Sleeping sickness threatens humans and livestock in rural areas of Africa, and has also been reported in Asia—and more recently, in the West via infected travelers. It’s caused by the trypanosome parasite, which is transmitted through the bite—or rather, the bite—of the tsetse fly. In its later stages, the disease attacks the nervous system, causing immense suffering and severe economic damage by killing cattle and other mammals.

There is currently no effective treatment or vaccine, as the parasite has developed resistance to available medications. But hope may lie in identifying a weakness in its life cycle—specifically, in the gut of the tsetse fly.

From Parasite to Parasite Hunter

Prof. Michaeli, of Bar-Ilan’s Faculty of Life Sciences and the Institute for Nanotechnology and Advanced Materials, has long studied the trypanosome family. This group also includes the parasite that causes Chagas disease, which attacks the digestive system and heart, and leishmania ("Jericho Rose"), a skin disease common in the Middle East.

Her research aims to identify the parasite's vulnerabilities by exploring the internal mechanisms that control its development in the host body. According to Michaeli, trypanosomes make for a fascinating model system because their gene expression is largely controlled after the transcription stage.

It All Happens Inside the Fly

In a recent study, Michaeli’s team uncovered the key role of a long RNA molecule named TblncRNA-23 in the trypanosome’s development. Although the molecule doesn’t code for protein, it regulates critical developmental processes in the parasite. Using CRISPR to delete  the gene or by overproducing  the gene encoding TblncRNA-23, the team uncovered several of its functions:

• It regulates the social motility of the parasite, which enables it to migrate within the fly’s body and eventually reach the salivary glands—ready to infect a mammal via a bite.
• It controls the transformation of the parasite into its metacyclic form, the stage that is infectious to humans.
• Silencing the gene entirely blocks the transmission of the parasite, effectively cutting off the infection cycle.

A First in Parasite RNA Research

The study involved detailed biochemical and molecular characterization of molecules regulated by TblncRNA-23, and identified a protein that binds with it. This marks the first study to define the role of a long non-coding RNA in the differentiation process of parasites during their complex life cycle.

Prof. Michaeli believes this research will pave the way to discovering similar RNA molecules that regulate parasites in human hosts, including  in relatives like leishmania and even the malaria parasite.

Her fascination with the trypanosome stems from both its complex post-transcriptional regulation and the urgent need for treatments and vaccines, which currently do not exist. “The only practical way forward,” she says, “is to silence or eliminate RNA molecules like the one we studied.”