Scientists discover parasite’s sex life could unlock human fertility secrets
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While malaria infected 238 million people in 2018, it infected 282 million people in 2024, and the number of deaths increased from 575,000 to 610,000 in the same period. Latest figures from the World Health Organization. Most of those who died were under the age of five.
These figures prompted leading science journal Nature Last week, the WHO will editorialize that its global target to end malaria epidemics by 2030 has been achieved overlooked.
But the fight to destroy one of humanity’s deadliest enemies has taken scientists to increasingly strange and hopeful places.
A foot soldier in the fight to prevent the disease, Dr. Nearly a decade ago, Claire Sayers went to the University of Melbourne’s School of Botany to start her PhD.
The ivy-covered botanical building seems like an odd place to study a disease spread by the vampire bug. What does malaria have to do with plants?
The terrifying parasite turns out to have a mysterious algal past, offering a critical new perspective on human fertility.
From ancient algae to those that destroy human blood
A single-celled malaria parasite was the reason Sayers turned to plant science. Plasmodium species – contain a critical organelle (a small cellular organ) similar to the chloroplast, the photosynthetic structure that makes leaves green.
ancient ancestor Plasmodium It was an aquatic photosynthetic algae. The tiny organ is a remnant of the parasite’s oceanic past; It no longer photosynthesizes but is critical to the growth of the malaria parasite.
“The chloroplast-type organelle has been conserved throughout evolution,” says Sayers, now a molecular biologist at the University of NSW. “That’s why my PhD advisor was at the School of Botany.”
Plant-like structure could serve as a new structure drug target In the asexual stage of malaria, when the parasite lodges in red blood cells and multiplies rapidly. Blood cells break down en masse, causing high fever, anemia, organ failure and brain inflammation.
But Sayers’ attention was soon drawn to another strange and fascinating element of malaria: the sexual phase.
To pursue this interest, she attended the Wellcome Sanger Institute in Cambridge, UK, and Umea University in Sweden, setting out on the path to finding an undiscovered key to fertility.
Zygotes, ookinetes and oocysts, oh my!
“It’s definitely underappreciated because it has such a complex biology,” Sayers says of malaria’s sex life. “But at the end of the day, the parasite produces an egg and a sperm cell, which is crazy.”
In the body of a malaria-infected person, a very small fraction (less than 0.1 percent) of the parasites produce precursor sex cells called gametocytes.
When a mosquito bites an infected person, some of these male and female gametocytes are absorbed into its intestine.
Once inside the mosquito, triggered by the drop in temperature, each male cell divides to form eight coiled sperm cells. This is one of the fastest examples on Earth of DNA replication in a complex organism: the process occurs within 15 minutes.
Sperm cells meet eggs to form a zygote, which then multiplies to form a motile cell called an ookinete. This cell anchors itself to the mosquito’s intestinal wall with a structure called an oocyst.
Within this durable cyst, thousands of infectious sporozoites form over the course of three weeks, until the cyst bursts and the tiny animals flock to the mosquito’s salivary glands, ready to infect the next host.
Disrupt this process and you stop the spread of malaria.
Genes key to malaria are also prevalent in human testicles
Sayers and his colleagues screened hundreds of the parasite’s genes to determine which ones were critical for this sexual reproduction.
They systematically excised the parasite’s genes. If they removed a gene and the resulting mutant Plasmodium If they couldn’t infect a rodent host, they knew the gene was important for fertility.
The process revealed a gene that codes for something. key protein complex.
If you disrupt this gene, “my parasites produce these sperm cells, but they don’t have nuclei,” says Sayers. Sperm cells come out wriggling and ready to rumble, but since the key DNA bundle isn’t there, they fire off the gaps.
“We are thinking about this [knocking out] “The gene stops the inheritance of the male genome, which we know is necessary for proper zygote development,” says Sayers.
It will be at least a decade before a discovery-based treatment can stop malaria transmission.
But the finding has relevance beyond the parasite. Using AlphaFold, a Google AI system that analyzes protein structures, Sayers and colleagues found that the key protein is found in nearly all sexually reproducing species, including us.
“This protein is extremely well conserved and enriched in human testicles,” says Sayers. “So what is he doing?”
Some papers show that some infertile men have disruptions in the protein gene in their DNA, confirming the idea that this may be important for human sexual health.
Male birth control pill?
In addition to shedding light on the mystery of male infertility (in many cases doctors can’t determine a cause), this finding could also spark the search for a new male birth control method. What if there was a drug that caused normal-looking sperm to fail to fertilize the egg?
Parasite can also be used to speed up other fertility studies. Most research is done on mice, which slows progress because unlike mice, which reproduce quickly, researchers have to wait for the animals to develop sexually. Plasmodium.
“We all have a common sexual ancestor that produced the first egg and sperm. The idea is that there is a core set of basic genes from which all sperm derive,” says Sayers.
“Because sperm is so important to life, we believe that even malaria sperm contains an essential set of proteins that we can use as a discovery tool to solve more complex human problems,” says Sayers.
Sayers has applied for funding to further explore these ideas.
“What we’re doing is very basic biology with these lofty blue-sky goals in mind,” he says of his unexpected finding. “This really confirms the importance of basic and fundamental sciences.”
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Angus Dalton is science correspondent for The Sydney Morning Herald.Connect with: X or email.
