College Profile 2023

Researchers use the common fruit fly to study the role genetics plays in human addiction

G eneticists Trudy Mackay and Robert Anholt lead a team of researchers from the Clemson University Center for Human Genetics (CHG) working to identify the genetic underpinnings of cocaine and methamphetamine consumption. The research could lay the groundwork for developing new drugs or repurposing already approved drugs to treat or prevent addiction in humans. A costly problem Substance abuse is one of the costliest public health problems in the nation. The U.S. Department of Health and Human Services estimates illicit drug use accounts for $193 billion in health care, productivity loss, crime, incarcera tion and drug enforcement. Scientists know genetics plays a role in human susceptibility to drug addiction. “Not everybody becomes addicted. Some people become very easily addict ed while others can be social drinkers or users and never become addicted, so we know there’s a genetic component,” Anholt said. The researchers use fruit flies in their research because approximate ly 70 percent of fruit fly genes have human counterparts. Plus, unlike humans, the flies’ genetic background and environment can be precisely controlled. In a previous study, Mackay and Anholt found cocaine use elicits rapid, widespread changes in gene expression throughout the fruit fly brain — and that the differences are more pro nounced in males than females. That study allowed male and female flies to ingest a fixed amount of sucrose or sucrose supplemented with cocaine over no more than two hours. Researchers then dissected the brains and dissociated them into single cells. Using next-generation sequencing technology, they constructed an atlas of gene expression changes after cocaine exposure.

behaviors in humans,” Mackay said. Measuring addiction Mackay’s lab developed the Drosophila melanogaster Genetic Reference Panel (DGRP), which consists of inbred fly lines with fully sequenced genomes derived from a natural population. Using those fly lines and a high throughput method that CHG Ph.D. student Spencer Hatfield and former postdoc toral fellow Joshua Walters developed to measure preference (choosing sucrose containing cocaine over plain sucrose when given the choice), the researchers will map variants associated with prefer ence and the genes associated with those variants. “We can look at those lines that have an innate preference and ask whether we can further develop the model for addiction. In other words, if they are ex posed repeatedly, will they start to prefer it more and develop adverse behavioral or physiological reactions? And despite that adversity, will they continue to show a preference for cocaine? That will be a real measure of addiction,” Anholt said.

EXTERNAL RESEARCH GRANTS FOR CHG

$20,457,590 TOTAL FUNDING $19,287,590 National Institutes of Health $1,000,000 European Union $170,000 Private foundations

“Through the previous grant, we learned a lot about the genetic basis of flies consuming cocaine or sucrose when they weren’t given a choice. But as the field is evolving, it is thought that preference is a better model of what could be considered addictive

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CLEMSON UNIVERSITY COLLEGE OF SCIENCE | 2023 COLLEGE PROFILE