Wake County

Tar Heel: Trudy Mackay works with fruit flies to solve genetic mysteries

NC State researcher Trudy Mackay in her campus lab with some of her subjects enlarged on screen via microscope.
NC State researcher Trudy Mackay in her campus lab with some of her subjects enlarged on screen via microscope. N.C. State

Trudy Mackay’s office has on display a painting of a fruit fly, another one sculpted out of wire, and a magnified image of one with a leg laid across the bottom of its face, in a pose reminiscent of “The Thinker.”

Her N.C. State University lab breeds and studies close to a million flies a year, packing them with different forms of DNA and getting them drunk, among other experiments, to explore the complex web of genetic and environmental factors that affect things such as their longevity and disease resistance.

One of her key achievements has been a massive effort to catalog 200 complete genetic fruit fly lines – allowing researchers across the world to tease out the genetic roots of traits that are crucial to plant, animal and human health.

In January, she was awarded the Wolf Prize for agriculture, an international award given by an Israeli foundation that is widely considered among the most prestigious and often serves as a stepping stone to the Nobel Prize.

The award, which comes with $100,000, adds to other accolades for a body of work that has used the humble flies to help researchers learn more about human traits and behavior. In 2010, she was elected to the National Academy of Sciences.

Fred Gould, an N.C. State entomologist who has collaborated with Mackay, says her work, funded largely by the National Institutes of Health, has both informed and inspired the work of countless other scientists.

He credits her perseverance and vision, but adds that her early years doing research before the mechanisms behind genetic variations were well understood helped propel her later work.

“She started out counting the bristles on fruit fly abdomens trying to understand why some had more than others,” says Gould, who is also a member of the National Academy of Sciences. “When it looked like the window was opening, she merged new ideas with all the knowledge she had gained and really moved the field forward.”

As for her species of choice, Drosophila melanogaster, Mackay started studying them in graduate school, and has remained with them throughout her 30-plus year career.

“It’s always been fruit flies,” she says, noting that she’s done projects with other animals and humans only in collaboration with other researchers. “Some people switch organisms, but not me.”

Drawn to genetic questions

Mackay grew up in Canada and says she was interested in the emerging field of genetics from the first time she learned about it in a 10th grade biology class. She liked the mathematics behind it, and the balance between chance and predictability.

“There are rules, but it’s random at the same time,” she says.

She went to Scotland for about a decade, where she earned her Ph.D. and continued as a researcher at the University of Edinburgh, which was renowned for its research in genetics.

But a tightening economy made research dollars in her field scarce, so she came to N.C. State in 1987, and has come to play a key role in the university’s genetics program.

A crop of early, high-profile studies in genetics were published while she was a Ph.D., opening up a new world of research that she was eager to pursue.

As an undergraduate, she had written her honor’s thesis on a species of aquatic worm. But as she found herself drawn to more pure genetic questions rather than ecological ones, she soon settled on the fruit fly as her primary research vehicle.

Her interest is in the complex combinations of genes that lead to traits that are important to human health, such as longevity and resistance to toxic substances such as lead.

Mackay says 75 percent of fruit fly genes have human equivalents, yet their genomes are easily manipulated, and their environments can be tightly controlled.

But her organism of choice has some drawbacks. They need to be used while they’re alive, for instance, and can’t be frozen for later research. Most flies live for about 50 days.

“Sometimes you have plant envy when it’s a holiday,” she says. “You can’t just put them away.”

Working as a team

In what looks like a cooler, but is kept at a balmy 25 degrees Celsius, are hundreds of tubes with eggs, larvae and full-fledged flies.

Mackay’s work involves both testing which combinations of genes cause certain traits and how the flies respond to the environment around them. In one line of study aimed at understanding alcohol tolerance and addiction, the flies are given ethanol. The drunk flies get suddenly active, then start dropping one by one to the bottom of the tube.

She says both sides of the coin must be explored in order to get an accurate picture of longevity, for instance.

“It’s not nature versus nurture,” she says. “It’s nature and nurture.”

A few key findings were that male and females differ in how genes affect them, and that some genes have an impact only in certain environments. In addition, the way that some genes work depends upon which other genes are present, creating an endless tangle of variations.

Lately, her focus on longevity has led her to consider quality of life, examining not only how long the flies live but when they stop doing the things flies like to do, such as flying toward lights and up tubes.

She runs her lab with her husband and about 30 students and other researchers, and she frequently partners with researchers in fields such as agriculture and animal science. She serves as associate director of a program that helps apply research in genetics to other fields.

“What used to be different sciences now collaborate to solve a problem,” she says. “Getting teams together is the way we do that.”

She says much of her career success resulted from the rapidly growing ability to map out genetic information. Even the paper she published in 2012, which fully cataloged 200 fly genomes, could now have been done for a fraction of the time and cost.

The advantage, she says, is reaching a dead end that you know may suddenly be reopened.

“The questions are pre-formed,” she says. “Then suddenly you’re able to answer them.”

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Trudy F. C. Mackay

Born: September 1952, Moncton New Brunswick, Canada

Residence: Raleigh

Career: Professor of Biological Sciences, N.C. State University

Awards: Wolf Prize for Agriculture, 2016; North Carolina Award for Science, 2011; O. Max Gardner Award, University of North Carolina system, 2007; Genetics Society of America Medal, 2004

Education: B.S. and M.S. Biology, Dalhousie University; Ph.D. Genetics, University of Edinburgh

Family: Husband Robert Anholt; four horses and three cats

Fun Fact: Mackay works closely with her husband, a fellow geneticist, but they didn’t meet in academic circles. They met through their mutual love of horses.