Jerusalem, 5 February, 2026 (TPS-IL) — Scientists have discovered a hidden step that helps the deadliest malaria parasite survive and multiply — a finding that could lead to new ways to fight the disease, Hebrew University of Jerusalem announced. The parasite relies on a brief but crucial phase, dubbed the “Crown” stage, to ensure a key internal structure is passed on correctly when it divides.
“By tracking both DNA replication and apicoplast development in real time, we found the details of these events and what controls them,” said Dr. Anat Florentin, who led the research at the university’s Kuvin Center for the Study of Infectious and Tropical Diseases and the Department of Microbiology and Molecular Genetics. “There are both signals from the nucleus and intrinsic organelle cues at play. These mechanisms could provide a new opportunity for drug development: if, for example, we can interrupt the communication between the nucleus and the apicoplast, we will stop the parasite from multiplying.”
According to World Health Organization figures, there were an estimated 250–300 million cases of malaria worldwide in 2023. Most cases and deaths occur in sub-Saharan Africa, which accounts for about 95% of malaria deaths. Children under five are especially vulnerable, making up the majority of fatalities.
The study focused on Plasmodium falciparum, the parasite responsible for most severe malaria cases worldwide. A tiny structure inside the parasite called the apicoplast, which humans do not have, is essential for its survival. Originally derived from a photosynthetic ancestor, the apicoplast now acts as a mini chemical factory, producing molecules like fatty acids and isoprenoids that the parasite needs to grow inside red blood cells.
Using a new live-imaging system that tracks subcellular structures across the parasite’s 48-hour life cycle, the scientists identified four stages in apicoplast development: Elongation, Branching, Crown, and Division. The Crown stage, lasting roughly one hour just before the parasite divides, was found to be a critical checkpoint. During this phase, the apicoplast stretches across multiple nuclei and attaches to centriolar plaques, structures that help organize cell division. This connection ensures that each daughter cell receives a complete, functional apicoplast.
The discovery points to practical ways to fight malaria. By targeting the Crown stage, future treatments could block communication between the parasite’s nucleus and its apicoplast, preventing it from multiplying inside red blood cells and reducing the severity of infection.
The study also revealed a “delayed death” effect: when daughter parasites are produced without a functioning apicoplast, they cannot survive. Exploiting this weakness could allow therapies to gradually eliminate the parasite over multiple generations.
To better understand what controls this process, the team used drugs that block specific replication steps. When nuclear DNA replication was inhibited with aphidicolin — a drug that prevents cells or parasites from copying their DNA and dividing — the researchers saw that apicoplast development stalled almost immediately.
The scientists then blocked the apicoplast’s own DNA replication with the antibiotic ciprofloxacin. They found that while the organelle elongated and branched, it failed to form the Crown structure. Without the Crown, the apicoplast could not attach to the centriolar plaques, and daughter cells were produced without it.
“This leads to what is known as ‘delayed death,’” explained Florentin. “The first generation of parasites may survive, but the next generation cannot, because without the apicoplast, the parasite is missing a structure it needs to make essential molecules and stay alive.”
According to the researchers, the newly uncovered Crown stage represents a promising target for future therapies. “By targeting the signaling mechanisms that coordinate the parasite’s DNA replication and apicoplast development, we could disrupt parasite reproduction and help stop malaria by preventing it from multiplying in the first place,” Florentin said.
The team hopes that these insights will pave the way for a new generation of drugs aimed at halting the parasite early in its life cycle.
The study was published in the peer-reviewed Journal of Cell Biology.
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