This inconspicuous insect helps U of M scientists unravel the
complexities of human health
Inside the lab of Nam Chul Kim, Ph.D., is one of the most powerful tools in the history of human health research.
For more than 100 years, this instrument has helped scientists understand the underpinnings of health and disease, shedding light on topics as diverse as genetic inheritance, cancer progression, brain development, infertility, immunity, and sleep. Its research prowess has led to half a dozen Nobel Prize–winning projects. And today, Kim is using it to illuminate the mechanisms that cause devastating neurodegenerative conditions like ALS and dementia.
No bigger than the tip of a match, it’s known in the research community as Drosophila. But you might know it by another name: the fruit fly.
Kim’s lab is home to more than 900 fruit flies, each of which is helping him better understand why ALS and dementia occur and how they might be treated—questions that, as of now, don’t have concrete answers.
But how can a tiny insect widely considered a household pest tell researchers anything meaningful about complex human illnesses? Behind the big eyes and translucent wings, Kim says, fruit flies aren’t too different from us.
“Flies actually share about 70 to 75 percent of genes with humans and close to 90 percent of disease-causing genes,” says Kim, an assistant professor in the Department of Pharmacy Practice and Pharmaceutical Sciences on the University of Minnesota Duluth campus. “[That] makes them a great model to study human health.”
Because of that strikingly similar genetic profile and an array of ideal characteristics, the fruit fly has become an unsung yet irreplaceable member of the medical community.
Strength in simplicity
Although the fly bears an important resemblance to humans at the genetic level, it’s a much less complex creature, Kim says. That simplicity is key to its usefulness.
Fruit flies have only four pairs of chromosomes, the structures in each living cell that carry genetic information. Humans have 23 pairs. With a genetic terrain that’s far easier to navigate, the fruit fly gives researchers the upper hand when it comes to finding, manipulating, and ultimately understanding how genes function.
And the insects are prolific procreators, too—they reproduce about once every two weeks—so it doesn’t take long to see the effects of genes and mutations on multiple generations.
This makes the fly an almost perfect model for researchers to learn the ins and outs of complex genetic behavior, says Aaron Goldstrohm, Ph.D., a member of the Masonic Cancer Center, University of Minnesota.
“Think of it like learning the basics of computer circuitry,” says Goldstrohm, also an associate professor of biochemistry, molecular biology, and biophysics, who uses fruit flies to understand the behavior of cancer-causing genes. “Would you rather learn on a simple machine like the fly or a complicated supercomputer like the human?”
Genetic research that would take years in mice or people can be done in a matter of weeks in fruit flies, he says, allowing scientists to test the results of thousands of genetic combinations quickly and produce a treasure trove of potentially useful data.
All this inherent convenience is amplified because the fruit fly remains remarkably similar to humans on a genetic level.
Pedro Fernandez-Funez, Ph.D., an associate professor on the U of M Medical School’s Duluth campus, studies neurodegenerative disease and shares a fly lab with Kim. In his research, he selects fruit flies that are carrying genetic mutations known to cause ALS and other diseases in humans. He then breeds them with flies that have mutations of other high-priority genes—those that are identical to their human counterparts but whose function in disease is still unknown—essentially playing the genetic lottery to see which combinations might make the disease less severe in future generations.
It’s a needle-in-a-haystack kind of pursuit, Fernandez-Funez says, but it’s possible with the fruit fly.
“Sometimes the fly offspring are healthier, sometimes they’re not,” he says. “But by doing hundreds, even thousands, of these crosses, we can gain a clearer picture of what’s going wrong in the fly, what we can do to fix it, and how we might be able to translate that to people with the disease.”
Pathways for treatment
Kim’s research takes a similar approach. His lab has narrowed in on a group of pathways in human brain cells that normally function like a garbage disposal; they remove unnecessary proteins before they cause a dangerous clog and ultimately lead to disease, like ALS or dementia.
There are more than 700 of these pathways in people, and Kim suspects one or a few disease-causing genes are to blame when the pathways malfunction. Finding those culprits, however, is a challenge. But the fruit fly makes it easier.
“With fruit flies, we can look at one specific gene at a time and figure out which one is involved in neurodegeneration,” he says.
Kim’s lab has already uncovered a few possible bad actors that might be causing problems. And he’s hopeful that those problematic genes could become treatment targets in the future.
“If we can find the mutant gene, we can cure the fly by removing [that mutation] genetically,” he says. “It’s kind of like gene therapy for the flies. Humans and flies are different, but the concept is the same. If we can identify the target in the fly first, then it’s possible we could move to people in the future.”
Kim’s research was supported in part by a grant from the Winston and Maxine Wallin Neuroscience Discovery Fund, created in 2011 to give scientists at the U the financial boost they need to pursue their boldest ideas related to brain health.
“The Wallin award allowed us to do things that weren’t happening anywhere else,” he says. “It was really helpful, and it gave me the freedom to test a new idea that has shown promise.”
Despite dwindling federal funding for fruit fly research and technological advances that make genetic analysis of people easier, the efficient fruit fly remains as valuable as ever, Goldstrohm says.
“You can’t erase the utility of the fruit fly,” he says. “Science takes a long time, and anything we can do to speed up the process is worth it.”
Fernandez-Funez agrees and says finding a cure for ALS, dementia, Parkinson’s, and other diseases won’t happen serendipitously. It will likely start in a lab like his, where scientists are relying on the simple power of fruit flies to master the mechanisms of disease and harnessing that knowledge to make a difference in people’s lives.
Unsurprisingly, he has a soft spot for his winged research partners.
“These flies are our babies,” he says. “They are very precious to us because they allow us to do so much.”