A fly goes about its business, buzzing here, buzzing there, but then it starts behaving strangely. His movements become slow and his abdomen swells. Its body produces white down.

At sunset, there is a sudden movement as the fly climbs – or “tops” – to a high place, such as the top of a small plant or stick, and extends its mouthparts. It spits out a sticky ooze that attaches it firmly to its perch, then it raises its wings and dies.

Below, other unsuspecting flies are hit by a shower of white spores bursting from the dead fly’s corpse. And the cycle begins again.

The white substance that engulfs these flies is a fungus called Entomophthora muscaewhich translates to “insect killer.” It is an obligate pathogen — entirely dependent on its host — which infects stolen and transforms them into “zombies” who carry out his will.

Discovered over 160 years agothe mushroom’s actions are as mind-boggling as they are macabre. Scientists have long wondered: how does the fungus manage to control the development of the fly? brain? How does he “know” to do it at a specific time of day? Which genes in his genome help him become a master manipulator?

Now, a series of experiments are beginning to unveil the science behind this strange 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 working with “zombie” houseflies, Domestic musca. Although initially attracted to the mushroom E. muscae Because he wanted to study obligate pathogens, “I was of course also fascinated by aspects of behavioral manipulation and how it worked,” he says.

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

De Fine Licht was particularly intrigued by reports describing how the fungus manipulates flies by making female fly carcasses attractive to healthy males. The males fly in and attempt to mate with the infected corpses – and quickly become infected themselves. To delve deeper into the nature of this deadly attraction, De Fine Licht and his team mixed infected and uninfected fly carcasses to extract and analyze chemicals and analyzed the air surrounding the corpses. They reported in 2022 that the the fungus releases volatile chemicals which attracts males.

However, it is not entirely clear whether the birds attract male flies with the promise of sex or nutrition, explains De Fine Licht. A working hypothesis is that they might simply be attracted to it because they think it’s food. “But when they get closer, they start to smell certain less volatile compounds from the corpses – and that elicits sexual behavior.”

Annette Jensen, an organismal biologist at the University of Copenhagen, also noticed something intriguing about how other insects reacted to the smell of dead flies. She and one of her students discovered that the earwig, an insect that feeds on other insects, is attracted to the corpses of sporulating flies infected with E. muscae and prefers to feed on them rather than uninfected corpses or corpses infected with other types of fungi. The scientists arrived at their conclusions after conducting experiments in which earwigs were placed between two types of corpses and were able to select which one to move towards.

“There could be something with the birds of Entomophthora muscae it also attracts predators,” says Jensen, who co-wrote an overview on fungi pathogenic to insects in the Annual Review of Entomology. “It’s probably super nutritious!”

Fruit flies join the list of victims

Most work on zombie flies has focused on houseflies, but Carolyn Elya, a molecular biologist and zombiologist at Harvard, set her sights on fruit flies after accidentally discovering zombified flies in her garden while she was a doctoral student at UC Berkeley. She had used rotting fruit as bait to capture wild fruit flies for experiments and was surprised to see dead flies with raised wings in this telltale pose, with white, fluffy spores on their abdomens. She quickly sequenced some DNA from the spores and confirmed her intuition: these fruit flies were victims of E. muscae.

Elya continued to infect Drosophila melanogastera well-established laboratory model that researchers around the world have studied for over a century. With that E. muscae-D. melanogaster systemshe wants to take advantage of the powerful Drosophila genetic toolbox and study the fly’s brain to understand how the fungus carries out its manipulation.

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

Elya also discovered that the fly’s circadian neurons, those that help it follow its daily rhythms, might be involved in time-sensitive altitude-seeking behavior. Silencing specific sets of these neurons in the brain inhibited summation activity in infected flies.

Elya also wants to understand this mind control from the mushroom’s perspective – and to that end, she, De Fine Licht and others recently sequenced the enormous E. muscae genome. Focusing on the strain that infects fruit flies, scientists reported discovering 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 – and so scientists hypothesize that this gene may be involved in the precise timing when infected flies ascend to the top at sunset, followed by their death.

Scientists also discovered many genes that could help the fungus fully utilize the fly’s tissues and nutrients. These included specialized genes encoding trehalase enzymes, which digest trehalose, the main sugar in hemolymph; proteins like chitinases that break down chitin in the fly’s exoskeleton; and lipases, which break down fats.

“That makes sense, right? Because these fungi are very specialized in how they use their hosts – not by killing them first then eating them later, which is a strategy used by many generalist pathogens – but instead, they develop inside insects. Elya said. “It’s important to be able to specifically target each tissue in their host.”

The search for additional clues continues, with researchers moving beyond the static genome to study the RNA copies of genes created when specific genes are active. In a research paper that has not yet been peer-reviewed, Sam Edwards, a postdoctoral researcher at Wageningen University in the Netherlands, De Fine Licht and colleagues reported their analysis of RNA in housefly heads at different times after a E. muscae infection. By determining which fly and fungus genes were active in the fly’s head, they hoped to gain insight into how the fungus manipulates the fly’s behavior.

The team detected the activity of a fungal gene similar to one called For example which is present in certain zombifying viruses. These viruses, like E. muscae, forcing their infected victims – in this case, the caterpillars – to move to high placesand in a motion more gruesome than that of their fungal counterparts, melt the caterpillars and release the virus particles beneath. THE For example embarrassed plays a role in this virus-induced summation behavior of caterpillarsthe researchers now want to know if the gene present E. muscae is the key to inducing the top of infected flies.

In a further twist, the pre-publication of De Fine Licht and a recent UC Berkeley study co-authored by Elya find this E. muscae may not work alone. The mushroom appears to be infected with a virus at the same time as it parasitizes house flies and fruit flies. It remains to be seen whether this virus helps the fungus control the fly.

Elya, De Fine Licht and others still want to know how the mushroom begins to be handled. One hypothesis is that E. muscae directly releases a chemical that activates the neurons involved in the fly’s behavior at the top. However, another hypothesis is that the all-consuming presence of the fungus and the resulting physiological changes in the fly trigger the fly’s own neurons to release chemicals to restart the process.

De Fine Licht wants the fly-zombie-mushroom system to be taught in schools in order to attract young science enthusiasts. He and Edwards recently published instructions on how to observe the zombifying fungus in the laboratory. “This could encourage secondary school teachers and others to try this if they wish,” says De Fine Licht.

Part of this operation involves collecting fly corpses in the field and isolating the fungus from them.

“Or you can try to infect healthy flies in the laboratory by associating them with the corpse,” explains De Fine Licht. “That might be the most fun, right? I’m trying to observe zombie behavior in a very small box.

This article was originally published in Knowable Magazinea journalistic enterprise independent of Annual Reviews. Register at newsletter.