Parasitic fungi can take over the brain for their own benefit. It gets worse.

A fly buzzes, buzzes here, buzzes there, but then it starts behaving strangely. His movements become sluggish, and his stomach swells. His body sprouts white fluff.

At sunset, there is a sudden burst of movement as the fly climbs — or “climbs” — to an elevated spot, such as the top of a small plant or stick, and extends its mouthparts. It spits out sticky slime that attaches it firmly to the perch, then lifts its wings and dies.

Down below, other unsuspecting flies are struck by a shower of white spores that fly from the corpse of a dead fly. And the cycle begins again.

The white substance that absorbs these flies is called fungus Entomophthora muscaewhich translates as “insect killer.” It is an obligate pathogen that is completely dependent on its host and infects flies and turns them into “zombies” who do his will.

Discovered more than 160 years agothe actions of the fungus are as awesome as they are creepy. Scientists have long wondered how mushrooms manage to control flies brain? How does he “know” to do this at a certain time of day? What genes in his genome help him become a master manipulator?

Today, a flurry of experiments is beginning to unravel the science behind this eerie mind control.

Deadly necrophilia

Henrik H. De Fine Licht, an evolutionary biologist at the University of Copenhagen, is one of the few people in the world who works with zombie houseflies. Homemade musk. Although at first I was drawn to the fungus E. muscae Because he wanted to study obligate pathogens, “of course I was also fascinated by aspects of behavioral manipulation and how it works,” he says.

These details are like fodder for a horror movie. After the fungus infects the fly, it does not directly enter the vital organs, but first begins to consume fats and other nutrients, gradually starving the fly to death but keeping it alive. Only when it runs out of non-vital organs to gnaw on does it begin to control the behavior of the fly, thus ensuring its continuity: by forcing the fly to seek a certain height and get stuck there, it ensures the widespread distribution of its spores.

De Fine Licht was particularly intrigued by the reports describing how the fungus manipulates flies, making the carcasses of female flies attractive to healthy males. Males fly in and try to mate with infected corpses — and immediately become infected themselves. To delve into the nature of this fatal attraction, De Fine Licht and his team chopped up infected and uninfected fly corpses to extract and analyze chemicals, and analyzed the air around the corpses. In 2022, they reported that the fungus releases volatile chemicals which lure males.

But it’s not entirely clear whether the volatiles attract male flies with the promise of sex or food, says De Fine Licht. The working hypothesis is that they may simply be attracted to them because they think it’s food. “But when they get up close, they start to smell some of the less volatile compounds in the corpses — and that triggers sexual behavior.”

Annette Jensen, a biologist at the University of Copenhagen, also noticed something intriguing about how other insects responded to the smell of dead flies. She and one of her students discovered that earwigs—an insect that feeds on other insects—are attracted to the corpses of spore-bearing flies that are infected E. muscae and prefers to feed on them rather than uninfected corpses or corpses infected with other types of fungi. The scientists came to their conclusions after conducting experiments in which earwigs were placed between two types of corpses and could choose which one to move towards.

“There could be something with volatile substances Entomophthora muscae it also attracts predators,” says Jensen, who wrote the review fungi pathogenic to insects in Annual Review of Entomology. “It must be extremely nutritious!”

Fruit flies join the list of victims

Most of the work on zombie flies has focused on houseflies, but Harvard molecular biologist and zombiologist Carolyn Ela focused her research on fruit flies after accidentally discovering some zombified flies in her yard while she was a graduate student at the University of California, Berkeley. She laid out the rotten fruit as bait to catch wild fruit flies for experiments and was surprised to see the dead flies with their wings up in such a frank position with white fluffy spores on their bellies. She quickly sequenced some of the DNA from the spores and confirmed her guess: these fruit flies were the victims E. muscae.

Elya went to infect Drosophila melanogastera well-known laboratory model that has been studied by researchers around the world for over a century. With this E. muscae-D. melanogaster systemshe seeks to use the powerful fruit fly genetic toolkit and study the brain of a fly to understand how the fungus performs its manipulations.

In a 2023 report, Elya and her colleagues showed that the fungus can secrete something into the fly’s “blood”—its hemolymph— which helps manipulate neurons in flies. When she injected the hemolymph of infected flies into uninfected ones, the latter began to behave as if they had been zombified.

Elya also found that the fly’s circadian neurons—the ones that help it keep track of its daily rhythms—may be involved in the time-sensitive behavior of height-seeking. Silencing specific sets of these neurons in the brain suppressed spike activity in infected flies.

Elya also wants to understand this mind control from a fungal perspective—and to that end, she, De Fine Licht, and others recently sequence of huge E. muscae the genome. Focusing on the strain that infects fruit flies, the scientists reported the discovery of genes similar to one called white collar 1which contains instructions for making a blue light sensor in a mold called Neurospora crassa. in N. crassa, white collar 1 plays a role in circadian rhythms, so scientists hypothesize that this gene may be involved in determining the exact timing of infected flies’ peak behavior around sunset, followed by their death.

The scientists also discovered many genes that can help the fungi make full use of the fly’s tissues and nutrients. These include specialized genes that code for trehalase enzymes, which digest trehalose, the main sugar in hemolymph; proteins such as chitinases that break down chitin in the fly exoskeleton; and lipases, which break down fats.

“That makes sense, doesn’t it? Because these fungi are very specialized in the way they use their hosts—not killing them first and then eating them, which is a strategy used by many generalist pathogens—they instead grow inside insects,” Elya says. “It’s important to be able to specifically target every last tissue in your host.”

The search for new clues continues, and researchers are moving beyond the static genome to study the RNA copies of genes that are produced when certain genes are active. In a research paper that has not yet been peer-reviewed, Sam Edwards, a doctoral student at Wageningen University in the Netherlands, De Fine Licht and colleagues reported their analysis of RNA in the heads of houseflies at various points in time after an E. muscae infection. By finding out which fly and fungal genes were active in the fly’s head, they hoped to gain insight into how the fungus manipulates the fly’s behavior.

The team discovered the activity of a fungal gene similar to the one called e.g which is present in some zombifying viruses. These viruses, like E. muscae, force their infected victims—in this case, caterpillars—to move to higher groundand in a movement more terrifying than that of their fungal counterparts, cause the caterpillars to molt and release the viral particles beneath them. The e.g gene plays a role in the virus-induced behavior of the apex caterpillarso the researchers now want to know if the gene in E. muscae is the key to induce apex in infected flies.

In a further twist, both the De Fine Licht preprint and a recent UC Berkeley study co-authored by Elya find it E. muscae may not work independently. Fungus appears to be infected with a virus at the same time that it parasitizes house and fruit flies. However, whether this fungal virus helps control the fly remains to be seen.

Elya, De Fine Licht and others still want to know how the mushroom begins to manipulate itself. One of the hypotheses is as follows E. muscae directly releases a chemical that activates the neurons involved in the fly’s behavior on top. However, another hypothesis is that the all-consuming presence of the fungus and the resulting physiological changes in the flies prompt the flies’ own neurons to release chemicals to start the process.

De Fine Licht wants the zombie-fly-mushroom system to be taught in schools to attract young science enthusiasts. He and Edwards recently published guidelines for how to observe a zombifying fungus in the laboratory. “It might encourage high school teachers and others to try it if they want to,” says De Fine Licht.

Some of these include collecting fly corpses from the field and isolating the fungus from them.

“Or you can try to infect a few healthy flies in the lab by placing them with the corpse,” says De Fine Licht. “This could be the most fun, right? Trying to observe the behavior of zombies in a small box.”

This article was originally published in Knowable magazineindependent journalistic initiative Annual Reviews. Subscribe to newsletter.