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Gnat Your Average Fly: Aale Agans ’25 Explores New Gene Editing Technique on Fungus Gnat

By Rebecca Goldfine
The senior is finessing a procedure to better study the genetics of the darkwinged fungus gnat, Bradysia coprophila, and possiby open the door to future biomedical breakthroughs.

Gnat Gnursery

Agans is doing cutting-edge research in experimental genetics as a lab assistant and honors student in Jack Bateman’s lab. They plan to attend graduate school next year to continue working in chromosomal genetics, specifically in a burgeoning field that Agans is hoping could contribute to new cancer therapies.

Fungus Gnats
Agans with some of their fungus gnats. They received a summertime Fellowship in the Life Sciences and a Fall Research Award from ºÚÁϳԹÏÍø±¬ÍøÕ¾ to fund their senior year honors project.

Yet one of the first topics to come up in a recent conversation with Agans was not exciting findings into intricate cell mechanisms. Rather, Agans described the tender way they care for the gnats in the lab.

Both Agans and Bateman do their best to ensure that their gnats—which are smaller than an eyelash and only live for four or so weeks—do not suffer.

“We make sure they live full lives, even though that is only for a month,” Agans said. “We give them all the food they want, they reproduce, and they’re not being injured.” (See the box at the end of the story for details about the lab's approach to fly care.)

Weird Gnats

Last summer, Agans started working with Bateman on the fungus gnat, a species new to the lab. Agans described the insect as an “up-and-coming model system for experimental genetics.” 

There is a reason the lab is fascinated with the fungus gnat. “They’re weird,” Agans said. For one, “they reject the paternally inherited chromosomes, essentially throwing them out so they only inherit the maternal genes. Why? We have no idea, because they’re losing genetic diversity and wasting energy.”

Despite not fully understanding this quirk, scientists recognize that it is unique in the world of insects (and certainly mammals). However, it is shared by one important entity—cancer.

Aale Agans ’25 with Jack Bateman
Agans and Linnean Professor of Biology Jack Bateman.

The fungus gnats eject their paternal genes in a process that is similar to cancer cell division and replication. Normally during cell division, chromosomes move to two opposite locations in the cell, creating a bipolar system. In fungus gnats—and in cancer cells—this process is monopolar, meaning all the chromosomes except the eliminated ones move into one pole before the cell divides.

“This [the fungus gnat] is one of the only species known to do this in non-cancerous cells,” Agans explained, making it a good natural system to study. Though scientists are not yet clear on how cancer cells, or fungus gnats, create “monopolar spindles,” trial drugs are being designed to target this system.

Cancer research has shifted its focus in recent years to drugs that take aim at particular genetic mechanisms. This way, treatments might avoid radiation and chemotherapy, which “impact everything in the body and which is why they have such strong side effects and make patients very ill,” Agans said. 

Weird Science

Weird gnats are right up Bateman's alley. He described himself as a big fan of “weird science.”

“My lab is drawn to phenomena that challenge our textbook views of how genes and chromosomes are supposed to behave,” he explained. “This species of fungus gnats is like a dream in that regard, they do so many things that they’re not supposed to do according to what we know from other species.”

Agans has been “a kindred spirit in their love for Bradysia,” Bateman continued. In addition to experimenting with DIPA-CRISPR, Agans is following up on research by former students in the lab—Sarah Conant ’24, Esther Ajibola ’27, and Gabe O’Brien ’26—on the gnats' early embryonic development, “which, as we’ve come to expect, is also super weird.”

“Aale is a really talented scientist,” Bateman said, “and I hope they are able to continue exploring oddballs of biology in the future.”

Molecular Scissors and Knitting Needles

While the gnat's developmental processes hold secrets that scientists would like to better understand, Agans said that “due to [it] being a new model species, modern experimental techniques have largely not been applied to the system.” This means the Bateman lab has had to come up with new technques.

To find a more efficient way to scrutinize gnat genetics, Agans last summer began experimenting with a new method to alter the genes not just of a maternal gnat, but also of her many babies. The only problem is it hadn't been tested on fungus gnats.

Generational Science

Not only does Agans love following the winding scientific path to new discoveries, they also enjoy teaching. They’re looking forward to one day working with the next generation of scientists.

Agans is the first in their family to attend college and identifies as LGBT. “I want to show young people, especially those who might be intimidated, that this is a job for you, that it isn’t just limited to a select group of people,” they said.

Next fall, they'll start a PhD program in molecular and cellular biology at the University of Connecticut.

Agans is using a technique that's a spinoff of CRISPR, the revolutionary, Nobel Prize-winning discovery that enables the deletion or insertion of genes, and which is opening the door to cures for a range of complex disorders, from cancer to Alzheimer’s disease.

“Through CRISPR, the underlying genetic mechanisms for phenomena can be tested, enabling the difficult jump from correlation to causation for implicating genes in being responsible for specific physical responses,” Agans said.

But the typical way researchers use CRISPR—injecting many tiny, individual embryos with a gene-editing molecular reagent—can be challenging, time consuming, or costly, especially if a lab is working with a species outside mainstream science, like the fungus gnat. Fruit flies, for instance, are much more common in research labs.

Agan's approach, using , involves injecting adults instead of embryos—which, when successful—is simpler, more efficient, and creates many more test subjects.

The first step Agans took last summer was a pragmatic one: they spent several weeks designing a miniscule but sturdy glass needle that could efficiently inject the tiny insects without harming them.

Then they scoured old scientific articles published in the 1920s and 1930s, when original research into fungus gnats first began. Gnat research dropped off after the ’30s (losing out to the fruit fly, which became the model system) and only recently has been revitalized. 

(To track down these journals, Agans received assistance from ºÚÁϳԹÏÍø±¬ÍøÕ¾’s Interlibrary Loan service. “They’re amazing!” Agans said, praising the librarians. “Within days, I’d get something from across the world.”)

The papers' authors revealed helpful insights into the development of the small flies. With guidance from these gnat pioneers, Agans began injecting maternal gnats, finally landing on a process that works—with many thanks to one uncooperative gnat that wouldn’t turn over to allow a jab into its belly area. This led Agans to discover that the best site for an injection, one that ensured a 95 percent survival rate, was in the back.

While this marked a step forward, offspring from these injected gnats did not inherit the edited genes. (The gene Agans wants to snip, as if with a “molecular scissor,” turns the insect’s normally black eyes to white, making it easy to see if the DNA has been affected.)

Close-up of the gnats
Adult gnats in their lab lair.

Agans returned to the old scientific journals. They found their answer in an article published in Czechoslovakia in 1921 about a closely related species. “Based on this paper, I found that I should try injecting the gnats four hours after they become adults,” Agans said. 

With this new information, Aale initiated a new round of injections, and now waits in anticipation for white-eyed gnats to hopefully emerge in large and consistent numbers. Some early results "show that the technique has potential, which is amazing! We just have to tweak it to make it work more often,” they said.

One tweak requires Agans and Bateman build a tool that increases the likelihood that the gnat's developing eggs accept the CRISPR reagent. Agans likes the tool to knitting needles, as it's a “three-dimensional DNA nanostructure” that wraps around the reagent. The nanonstructures can then be tagged with a little marker that “says, ‘Hey, I’m this native protein, you can take me in!’” Agans explained.

If Agans can make this process work consistently, it could open the door to new research avenues, both with fungus gnats and other insects, “like the barley midge, which destroys millions of dollars’ worth of crops.” The fungus gnat, too, is a common agricultural pest.

After graduating in May, Agans will start a PhD program at University of Connecticut's Department of Molecular and Cell Biology to continue exploring the world of fungus gnats, their monopolar spindles, and other genetic curiosities of non-model systems.

“I love science a lot. I want to understand how things work,” they said. “And it needs to be done, so why not me?”

Letting Gnats be Gnats

The Bateman lab tries to take care of its fungus gnat test subjects. During their three-week larval stage, the young squirmy grubs are fed organic shiitake mushroom powder mixed with yeast, for protein. “If the shiitake had any pesticides, that would affect them,” Agans said, explaining the gourmet meal.

Once the gnats metamorphose into mouthless adults, the little creatures are intent on one mission only: to reproduce, which Agans is happy to let them do, since it leads to bountiful testing subjects for the lab.

If Agans needs to stab a gnat with a needle, they anesthetize them with carbon dioxide to prevent possible discomfort. “We don’t know if they feel pain,” they said. “But we know they respond to negative stimuli.” Agans’s job then is to move fast, since the gnat’s health declines if it’s over exposed to CO2.

“Biomedical ethics is giant,” Agans said, explaining why the lab takes these steps. Though testing on mammals and insects is necessary to help find cures for human diseases, they argue that scientists should not forget they are working with living creatures.