Sunday, October 13, 2024

The fruit fly revolutionized biology. Now it’s boosting science in Africa

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When Amos Abolaji returned to Nigeria from a year abroad, he brought home a strange souvenir — two jars full of fruit flies.

The biochemist had been conducting postdoctoral research at the Federal University of Santa Maria in Brazil on the health effects of certain pollutants. He had used laboratory rodents while working on his Ph.D. in Nigeria and wasn’t previously exposed to the use of fruit flies. But when Abolaji joined toxicologist Joao Batista Teixeira da Rocha’s lab in Brazil, “he told me he stopped the use of rodents for research.” Rocha had switched to using the fruit fly Drosophila melanogaster.

After working with Rocha, Abolaji understood the fruit fly’s power. “The fly has a high degree of advantages compared with rodents, especially in resource-limited regions,” Abolaji says. They’re cheap, easy to raise, require little lab space and can bring fast results — and they’re poised to boost biomedical research across Africa.

When Abolaji returned to Nigeria in 2014 and became a professor at the University of Ibadan, he took his jars and converted his office into a miniature fly lab. He’s now a key figure in a growing movement to establish fruit fly research across Africa, where rodents are still the go-to subject in studies of genetics, developmental biology, toxicology and other fields of biomedical research.

In Africa, fruit fly studies can help address urgent public health needs, connect local scientists with the global research community and build research capabilities across the world’s second-largest continent.

“We use [the fruit fly] as a tool to be able to carry out not just research,” Abolaji says, “but to raise [the] next generation of scientists.”

The history of the fruit fly in the lab

Studying animals to gain insights into human biology and medicine goes back millennia, at least as far back as the ancient Greeks. By the 12th century, Arab physician Ibn Zuhr was testing surgeries on animals before performing them on humans. In the mid-19th century, the Norway rat became a mainstay of lab research because the ubiquitous pest was easily acquired and survived well in captivity.

The fruit fly didn’t enter the lab until 1900, when Harvard entomologist Charles Woodworth began breeding them en masse for reasons that are not entirely clear. He recommended them to researchers studying genetics — a field still in its infancy at the time — and from there the potential of the fruit fly spread through word of mouth.

The Drosophila boom took off in earnest around 1910, after Thomas Hunt Morgan set up his famous Fly Room at Columbia University. Cluttered with flasks full of fruit flies and bunches of bananas dangling from the ceiling, the Fly Room hardly compares to the sleek and sterile labs of today. But in that room, Morgan made the groundbreaking discovery that genes are passed down to the next generation on chromosomes (SN: 2/7/22).

Thomas Hunt Morgan (inset) set up the famous Fly Room at Columbia University (shown below in 1918). As a model organism, fruit flies helped launch the field of genetics in the early 20th century.American Philosophical Society

The fruit fly’s short life cycle allowed the field of genetics to take flight. Although rats reproduce fast for mammals — pregnancy is typically 21 days and females reach sexual maturity two to three months after birth — they have nothing on fruit flies. They can produce a whole new generation in just 10 days. This, plus their small genomes, makes the fruit fly a powerful tool for studying how genes and traits are passed down from one generation to the next (SN: 5/17/19).

Drosophila are also used to study how embryos develop into adults and to test the biological effects of chemicals. (Because rodents are even more closely related to humans, they remain popular model organisms for studying mammal-specific traits and in clinical drug testing.) Over the last century, nine scientists have won Nobel Prizes based on work done with fruit flies.

Abolaji’s Drosophila lab is in Ibadan, the third-most populous city in Nigeria and capital of the southwestern state of Oyo. When I reached him over Zoom, he presented a slide show of his history with Drosophila. “I thought it would be good if I just share it like a story,” he told me.

Several years after bringing fruit flies back from Brazil in 2014, Abolaji was approached by DrosAfrica, an organization founded in 2013 to expand the use of Drosophila by African biologists. A trio of Spanish researchers started DrosAfrica after a workshop in Uganda on using insects in neuroscience research. Physiologist Sadiq Yusuf, who was then the deputy vice chancellor of Kampala International University and later went on to found a charity supporting research development in Africa called TReND, had organized the workshop.

He made many significant contributions, including discovering that embryonic cells cluster together based on what anatomical structure they develop into, with their fate controlled by certain genes. García-Bellido, it’s been said, “put Spain on the scientific map.”

The Spanish group had recognized that African researchers were primed to use fruit flies to accelerate the continent’s research, which is what had happened in Spain a few decades earlier.

A photograph of Amos Abolaji
Amos Abolaji, a biochemist at the University of Ibadan in Nigeria, is a key figure in a movement to establish fruit fly research across Africa.DRTC

From Morgan’s Fly Room, D. melanogaster spread quickly to other research labs in North America and Europe. But not every country caught fly fever. In Spain, virtually no one worked with the fruit fly until Antonio García-Bellido returned to his native country after finishing a research fellowship at Caltech in the 1970s. Once home, the developmental biologist established a Drosophila lab.

“Then he trained three people, and then these three people trained other people,” says María (Lola) Martín-Bermudo, a geneticist at Pablo de Olavide University in Seville and a DrosAfrica cofounder. “Now there are lots of Drosophila labs in Spain.”

To jump-start a similar spread of knowledge in Africa, Abolaji and DrosAfrica organized a workshop at the University of Ibadan in 2017, which brought in experienced fruit fly researchers from as far as Spain and the United Kingdom to teach attendees Drosophila biology and how the fruit fly can be used to study neurodegeneration, cancer and toxicology, as well as help with drug discovery. “That workshop was one of the major turning points in my research,” Abolaji says.

The workshop hosted participants from elsewhere in Africa, including Uganda, Rwanda and Ghana. One participant, a young woman from northern Nigeria named Rashidatu Abdulazeez, traveled 18 hours over two days to attend.

Meeting Africa’s urgent public health needs

Long before arriving at that workshop, Abdulazeez had already become hooked on fruit flies. But she didn’t have a jar of flies from another lab to start her work — she had to catch them herself.

She’d read that the flies could be trapped outdoors, but nothing she tried had worked. While earning a master’s degree in population genetics, Abdulazeez stayed with her auntie while trying to catch flies in the city of Kaduna in northwestern Nigeria. “[Perhaps] they don’t want to stay far from humans,” her auntie suggested.

Thinking the flies might prefer human trash to other lures, Abdulazeez left out a bowl of rotten fruit overnight. “I had a dream that I caught lots of Drosophila,” Abdulazeez recalls with a laugh. In the morning, her dream had come true.

In 2016, after solving the fly-catching problem, she published an analysis of the genetic variation of Nigeria’s D. melanogaster populations.

Like Abolaji, Abdulazeez had to learn a lot about Drosophila on her own. But it was worth it. “I began to fall in love [with fruit flies] because I was just so amazed by the fact that we had so much in common,” she says, referring to the 60 percent of our DNA that we share with fruit flies. And importantly, 75 percent of the genes that cause disease in humans are also found in the flies.

Abdulazeez is now a lecturer (akin to a professor) at her alma mater, Ahmadu Bello University in Zaria. Toward the end of our video call, she took me into the hallway as she headed to a meeting and pointed out the poster on her lab’s door: a black-and-white image of a fruit fly peering through a microscope, with the words “Small Lab Big Science” blazoned across the top.

A photograph of Rashidatu Abdulazeez in her fruit fly research lab in Nigeria
Rashidatu Abdulazeez of Ahmadu Bello University in Nigeria founded Droso4Nigeria, an organization that brings fruit fly lessons to biology classes in secondary schools.R. Abdulazeez

The “Big Science” benefits of Drosophila as a model organism stem from not only its similarities to us, but also its key differences, like being easy to care for. Starting a Drosophila lab can require as little as a jar of flies and a handful of microscopes, while a colony of lab rats can take up an entire room’s worth of cages. The ease of using fruit flies is a huge boon for a continent with many local public health concerns but little local research funding.

“I desire to carry out research that will have beneficial effects on humans,” Abolaji says. Some pollutants in the environment can predispose people to cancer, diabetes, Parkinson’s disease and a whole host of other afflictions, he says, and he uses fruit flies to understand why.

One pollutant that Abolaji has studied is 4-vinylcyclohexene, a by-product of the manufacturing of pesticides, plastics and tires. Plastic manufacturing has been growing in Nigeria, from 120,000 tons in 2007 to an estimate of more than 500,000 tons in 2020, meaning more and more workers are potentially being exposed to VCH. In monkeys and rats, VCH is known to destroy follicles in ovaries, so there’s concern that exposure could cause early menopause in humans.

“A woman that is working in an environment where such compounds are manufactured or produced or used as by-­products, [who is] supposed to reach menopause at 56, may reach menopause at 30 or 35,” Abolaji says.

But how VCH harms ovarian follicles was elusive. Abolaji got a hint by exposing Drosophila to VCH and analyzing the resulting changes in the fruit fly’s gene activity and physiology. The chemical causes the production of toxic types of oxygen-­containing molecules known as free radicals, which damage cells.

In Tunisia, Hayet Sellami hopes to leverage the power of fruit flies to create a drug-screening factory, speeding up the process of identifying new medical treatments. Sellami, a medical doctor and researcher, says her journey with Drosophila began with a pair of workshops in 2018 and 2019 hosted by her institution, the University of Sfax, and organized by DrosAfrica and a professional network of scientists called Young Tunisian Researchers in Biology. Impressed by the workshops, university administrators approved creating a Drosophila research unit.

“Our research unit is the first [in Tunisia] to use Drosophila as a low-cost model for research,” Sellami says. She hopes to begin fruit fly research in earnest this year, and once the lab is fully up and running, researchers will be able to quickly screen prospective drugs by testing them on fruit flies. If a drug seems promising, the next step will be tests on rodents. Using Drosophila as a first pass for drugs will save valuable time and money that would otherwise be spent raising and caring for expensive rats and mice.

One of Sellami’s interests is using the flies to test potential antifungal drugs. “This [is] a good opportunity to enhance our university and to have practical research,” she says, and lead to “better health care for our people.”

In a 2022 study, 63 percent of the fungus Candida albicans collected from pregnant Tunisian women’s vaginas was resistant to the common antifungal drug fluconazole. C. albicans is often harmless, but it can cause yeast infections that can lead to rare pregnancy complications. So finding new antifungal drugs is a pressing concern.

Boosting fruit fly research across Africa

The University of Sfax is following in the footsteps of the University of Ibadan, where the small fly lab Abolaji founded in 2014 has blossomed into the separate Drosophila Research and Training Centre. It serves as a regional hub for scientists interested in working with fruit flies. Sellami hopes that Sfax becomes a hub for North Africa. By investing in fruit fly research, African institutions also now have the chance to join the iconic insect’s global fan club.

A photograph of a laboratory tube full of fruit flies held by a pair of gloved hands
Fruit flies (shown in a tube) are a popular model organism in biology partly because they are easy to care for.IRD/Vectopole Sud/PATRICK LANDMANN/Science Source

Biologist Ross Cagan of the University of Glasgow in Scotland was one of the Drosophila researchers recruited by DrosAfrica to run workshops. He now collaborates with both Abolaji and Sellami on medical research that not only has health implications for Africans but for people globally.

“My lab develops some technology we call ‘fly avatar,’” Cagan says. Using gene editing, specific genetic mutations of individual cancer patients are introduced into fruit flies. The goal is to capture the complexity of a patient’s cancer in a group of Drosophila flies to study how those mutated genes affect tumor progression and how the cancer responds to drugs.

“One of the questions on the table is, what’s the difference between a European tumor and an African tumor?” Cagan says. Abolaji’s team is generating fly avatars that mimic the genetics of Nigerian patients with colorectal cancer.

Abolaji is “somebody that the more you get to know him, the more impressive he becomes,” Cagan says. “That collaboration is going beautifully. It is truly growing out of Nigeria.”

The biggest money for research still lies in Western institutions, and writing grants to get the funding for ambitious projects is difficult even for scientists in North America and Europe. Western collaborators can help African researchers navigate this path. Sellami recently submitted a proposal to Horizon Europe, a seven-year funding initiative of the European Union, in collaboration with Cagan to support Sfax’s research into personalized medicine with fly avatars. Sellami and Abolaji have also teamed up to submit a proposal to another EU funding initiative, Erasmus+.

One thing that makes these international collaborations stand out is that African scientists are guiding the research questions, says Marta Vicente-Crespo, cofounder of DrosAfrica and a program manager at the Nairobi-based Consortium for Advanced Research Training in Africa. Often in such collaborations, African researchers get what’s been dubbed “stuck in the middle.” They may collect data, but not analyze or interpret it, while Western scientists lead the project and claim the more prestigious first and last authorship spots on papers.

“There has been a lot of tokenization,” Vicente-Crespo says. “Things are changing, but very slowly.”

A photograph of researchers looking through microscopes in a biological lab at the Drosophila Research Training Centre in Nigeria
The Drosophila Research and Training Centre in Nigeria helps train scientists on how to use fruit flies in their research.A. Abolaji

The legacy of colonization has left many areas of Africa with little capital, which means students looking to do research often have to fund the projects themselves. “We don’t have funding,” Abdulazeez says. “When you come for any of your degrees, you basically sponsor yourself.” Because rodents are expensive, students often can’t afford to use many, resulting in studies with low sample sizes and thus conclusions that aren’t reliable enough to publish.

“They get their degree, but the science doesn’t go anywhere,” Vicente-Crespo adds.

By using Drosophila, money that might have gone to feeding a few rodents for several weeks can instead turn into thousands of fruit flies. Abdulazeez estimates that one mouse costs about 1,000 naira, the Nigerian currency; buying 80 of them would cost more than many Nigerians make in a month.

A fruit fly homecoming

There is a poetic side to D. melanogaster’s rise in African research — like humans, the fruit fly evolved in Africa before spreading around the world. Though they came to dominate the globe through an association with humans — living off our food waste — they once lived more pastoral lives. Researchers in 2018 found a population of D. melanogaster living in a forest in Zimbabwe, unaffiliated with humans. These flies fed and laid their eggs on the fruit of marula plants. The Indigenous San people of southern Africa historically collected marula fruit and stored them in caves, where the fruit fermented. Researchers speculate that this shared use of marula ultimately sparked the human-fly connection that persists to this day.

Abdulazeez is most passionate about the ecology and evolution of fruit flies. For now, though, as the leader of a new research group, she’s focusing on more urgent health problems — like lead poisoning — and on inspiring the next generation of Nigerian biologists. “We still have people who are yet to accept the fact that we could use these flies for wonderful things,” she says.

To combat this problem, she founded Droso4Nigeria, an organization that works to bring Drosophila-based biology lessons into Nigerian secondary schools and trains teachers to use the fruit fly in the classroom.

Abolaji also stresses the importance of education and training. “The ultimate goal is to raise and develop the next generation of scientists in Africa,” he says.

While international grants and collaborations are important, the ongoing success of Africa’s Drosophila-fueled research boom wouldn’t be possible without the passion, talent and resourcefulness of the African scientists leading the way. During our video call, Abolaji showed me the temperature-controlled incubator he uses to raise flies; a new one can cost upward of $10,000, but Abolaji fashioned his out of an old drink chiller (the kind you’d pull a bottle of soda from at the grocery store) for less than $500.

“Europe will not develop Africa for us. America will not develop Africa for us,” Abolaji says. “We are the ones to actually build Africa.”



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