Malaria research: Scientists discover parasite’s sex life could unlock human fertility secrets
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Malaria infected 282 million people in 2024, compared with 238 million in 2018, and the death toll climbed from 575,000 to 610,000 over the same period, according to the latest World Health Organisation figures. Most of the dead were younger than five.
Those numbers prompted leading science journal Nature to editorialise last week that WHO’s global goal of ending malaria epidemics by 2030 has slipped out of view.
But the fight to vanquish one of humanity’s deadliest enemies has led scientists to increasingly strange and hopeful places.
One footsoldier in the battle to foil the disease, Dr Claire Sayers, walked into the University of Melbourne’s School of Botany about a decade ago to begin her PhD.
The botany building, wreathed in ivy, seems a strange place to study an illness spread by a vampiric bug. What does malaria have to do with plants?
It turns out the horrid parasite has a mysterious algal past – and offers a critical new insight into human fertility.
From ancient algae to human blood-buster
Sayers was drawn to plant science because the malaria parasite – a single-celled Plasmodium species – contains a critical organelle (a teeny cellular organ) similar to chloroplast, the photosynthetic structure that makes leaves green.
The ancient ancestor of Plasmodium was a water-dwelling photosynthetic algae. The tiny organ is a relic of the parasite’s oceanic past; it no longer performs photosynthesis but is critical for the malaria parasite’s growth.
“It’s maintained the chloroplast-type organelle through evolution,” says Sayers, now a molecular biologist at the University of NSW. “That’s why my PhD supervisor was in the School of Botany.”
The plant-like structure could serve as a new target for drugs during malaria’s asexual stage, when the parasite worms into red blood cells and rapidly replicates. The blood cells rupture en masse, inflicting high fevers, anaemia, organ failure and inflammation of the brain.
But Sayers’ attention was soon snatched by another odd and fascinating element of malaria: its sexual stage.
She travelled to the Wellcome Sanger Institute in Cambridge, UK, and on to Umea University in Sweden to pursue that interest – and stepped onto the path to finding an undiscovered key to fertility.
Zygotes and ookinetes and oocysts, oh my!
“It’s totally underappreciated because it’s complicated biology,” Sayers says of malaria’s sex life. “But at the end of the day, the parasite does make an egg and sperm cell, which is crazy.”
Within the body of someone infected with malaria, a tiny proportion of the parasites – less than 0.1 per cent – produce precursor sex cells, called gametocytes.
When a mosquito bites an infected person, some of those male and female gametocytes are sucked into its gut.
Triggered by the drop in temperature once taken into the mosquito, each male cell divides to create eight wriggly sperm cells. It’s one of the fastest instances of DNA replication on Earth within a complex organism: the process takes place in 15 minutes.
The sperm cells meet with the eggs and create a zygote, and then that replicates to form a mobile cell called an ookinete, which fixes itself to the wall of the mosquito’s gut in a structure called an oocyst.
Within this hardy cyst, thousands of infectious sporozoites form over three weeks, until the cyst bursts and the tiny beasties swarm into the mosquito’s salivary glands, ready to infect the next host.
Disrupt this process and you stop malaria transmission.
Genes key to malaria – and rife in human testicles
Sayers and her colleagues screened hundreds of the parasite’s genes to pinpoint which ones were critical to this sexual reproduction.
They systematically snipped out genes from the parasite. If they removed a gene and the resulting mutant Plasmodium couldn’t infect a rodent host, they knew that gene was important to fertility.
The process revealed a gene that codes for a key protein complex.
Disrupt that gene, Sayers says, and “my parasites produce these sperm cells but they have no nucleus”. The sperm cells come out wiggling and ready to rumble, but with no key bundle of DNA, they’re firing blanks.
“We think that [knocking out] the gene is stopping inheritance of the male genome, which we know is essential for proper zygote development,” Sayers says.
It will take at least a decade before a treatment based on the discovery might work to halt malaria transmission.
But the finding has relevance beyond the parasite. Using AlphaFold, a Google AI system that analyses protein structures, Sayers and her colleagues found the key protein exists in almost all sexually reproducing species, including us.
“This protein is extremely well-conserved and it’s enriched in human testes,” Sayers says. “So what is it doing?”
Some papers show some infertile men have disruptions to the protein’s gene in their DNA, which validates the idea it could be important for human sexual health.
A male contraceptive?
As well as shedding light on the mystery of male infertility (for most cases, doctors cannot establish a cause), the finding could spark a hunt for a new male contraceptive. What if there was a drug that resulted in normal-looking sperm incapable of fertilising an egg?
The parasite could also be harnessed to fast-track other fertility studies. Much of the research relies on mice, which slows progress because researchers must wait for the animals to sexually develop, as opposed to the fast-replicating Plasmodium.
“We’ve all got this common sexual ancestor that produced the first egg and sperm. The idea is that there’s this core set of fundamental genes from which all sperm has arisen,” Sayers says.
“Because sperm is so important to life we believe that there is a fundamental set of proteins even in malaria sperm that we can use as a discovery tool to get at more complicated human issues,” Sayers says.
Sayers has applied for funding to further explore these ideas.
“What we do, it’s very fundamental biology, with these lofty blue-sky aims in mind,” she says of her unexpected finding. “It really validates the importance of basic and fundamental sciences.”
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Angus Dalton is the science reporter for The Sydney Morning Herald.Connect via X or email.
