New findings on how malaria parasites invade human cells yield proof of concept for new antimalarial drug

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For nearly half a century, scientists have known that malaria parasites force their way into human red blood cells through a ring-shaped structure called the moving junction. What no one could work out was what it actually does. The structure assembles, does its job and dissipates in the space of 60 seconds—gone before anyone can get a close look.

A team at Columbia University has now finally caught the moving junction in the act. By freezing parasites at the onset of invasion and lifting the intact complex straight out of the cell, the researchers have obtained the first high-resolution view of its three-dimensional structure. What they saw overturned a decades-old assumption about how the parasite gets in. Rather than a passive doorway, the moving junction turns out to be a molecular machine that actively remodels the host cell's membrane to help the parasite force its way inside.

The findings, published in Cell, detail how the team obtained the structure and then used it as a blueprint to design a mini-protein, from scratch, that blocks invasion—a proof of concept for a new kind of antimalarial drug.

Malaria still kills roughly 600,000 people a year, the overwhelming majority of them young children in sub-Saharan Africa, and the parasite is steadily becoming resistant to frontline drugs. The disease starts with a single event: a parasite breaking into a red blood cell. In an infected person, trillions of parasites are released and invade every 48 hours in synchronized waves. This rhythmic cycle of rupture and reinvasion drives the periodic fevers malaria is known for.

The same moving junction machinery is used across every species and every stage of the parasite's life cycle, which has made it one of the most sought-after targets in malaria research. Block it, and you stop infection at its source.

"We've known for decades that this structure is essential for the parasite to get into a cell, but not how it actually works," said Chi-Min Ho, an assistant professor in the Department of Microbiology and Immunology at Columbia University Vagelos College of Physicians and Surgeons and the study's senior author. "Pulling it directly out of the parasite intact let us finally ask that question directly."

The moving junction has been a puzzle since 1978, when scientists first observed a mysterious thickening of the membrane where parasite meets cell in electron microscopy images