Department of Biology

A new study led by Orie Shafer, Indiana University biology professor and a Linda and Jack Gill Chair at the Gill Institute for Neuroscience, with IU postdoctoral fellow Abhilash Lakshman, Ph.D., and IU undergraduate student Reed Evans, is reshaping how scientists study sleep by revealing that fruit flies experience multiple distinct sleep states rather than a unitary state. 

Published in Current Biology, the research uncovers previously hidden mechanisms of sleep regulation and renews the promise of fruit flies as a powerful genetic model for understanding sleep in humans. 

“At the heart of this is one of the stars of IU Bloomington Biology, the fruit fly, Drosophila,” Shafer said. The Bloomington Drosophila Stock Center houses the world’s largest collection of fruit flies. 

“The fruit fly has been a powerhouse for revealing fundamental mechanisms that ultimately prove to be broadly relevant to all animals,” Shafer said. 

There are two major mechanisms of sleep regulation. One of them is the clock in your brain, the circadian clock. The other is the homeostatic control of sleep. That is, if you've been awake a long time, you get sleepy. And if you miss a night of sleep, you're even sleepier. The longer you've been awake, the stronger the drive is to sleep. Shafer said, “It's like a temperature homeostat. It's there to ensure the right  amount of sleep.” 

Three of Shafer’s colleagues received the Nobel Prize in 2017 using the fruit fly to figure out how the circadian clock works. It was discovered that the same mechanism is operating in our body to control the timing of sleep. 

“25 years ago, two independent groups showed that these flies sleep,” Shafer said. “It wasn't clear at the time whether something like a fly slept. These two groups made a very, very strong case that there is a sleep-like state in flies. And that was extremely exciting, because then we could do for sleep what people had done for clocks and body pattern formation and the basis of mutation.” 

There was great hope that, having established sleep in the fly, researchers could identify genes that govern sleep and uncover a mechanism. 

“The field has discovered over 200 sleep genes, but they're not really sleep genes, because we have no mechanism for them. We’ve been thinking about sleep in a narrow way and have not recsonsidered how we measure sleep in flies,” Shafer said. 

“So, what this study does is to say is that we haven't been looking at sleep properly. The way that the field has defined sleep has been too simple. It captures too many things, and most critically, it considers sleep to be one single state.” 

The researchers have not identified REM and non-REM sleep in the flies. “We have shown, inspired by some work by others, and by a lot of new work by us, that there are shallower, briefer forms of sleep, and there are longer, deeper forms of sleep. And when you account for the existence of different sleep states in the fly, now you can really measure homeostasis. You can measure the homeostatic control of sleep in a way that we haven't been able to do before. And what that means is, now we need to revisit this idea of using the fly to discover genetic mechanisms of sleep. And by recognizing sleep states that are strongly controlled by the homeostat, we've got a much better grasp of sleep in the fly.” 

Shafer said they can now make some progress that they couldn't before. “That progress could have a significant real-world impact,” he said. “If we could identify the real mechanism of sleep homeostasis, it would have a huge benefit on not only health, but also public safety. Our airline pilots are sleep deprived, our bus drivers are sleep deprived, and our truck drivers are sleep deprived.”  

According to the Centers for Disease Control and Prevention, about 1 in 25 adult drivers report having fallen asleep while driving, and many more admit to driving when they were sleep deprived. 

“We're revisiting what they tried 25 years ago, which was to use a forward genetic screen. We've got wonderful people here, including Thom Kaufman, distinguished professor emeritus of biology, and Kevin Cook, senior scientist in biology, who have this wealth of information about how to do this. With their help, we can do forward genetics in a way we couldn't have done anywhere else.” 

Shafer said his postdoc, Abhilash Lakshman, has driven the work and has long played an important role in rethinking sleep in his lab. Lakshman is the first author on the paper. Shafer also points out that the middle author is undergraduate student Reed Evans. 

“IU Bloomington is the capital of Drosophila genetics for the world,” Shafer said. “So it's a really fun place to be doing this research.” 

The study, “Recognition of distinct sleep states in Drosophila uncovers previously obscured homeostatic and circadian control of sleep,” appears online in Current Biology and will be published in the February 23, 2026 issue.