An unsolved mystery: Why are we sleepy when sick?

David Raizen, a professor of neurology, alongside PURM student Hina Sako, spent the summer moving forward research examining how sickness affects sleep.

Researcher peering through microscope.
David Raizen, left, and PURM student Hina Sako working in the Raizen Lab.

In clinic, David Raizen, a professor of neurology at the Perelman School of Medicine, would encounter patients reporting fatigue associated with chronic diseases like rheumatological disease or multiple sclerosis. He eventually realized how poorly understood sickness-related fatigue is.

“As clinicians, you’ll hear someone say the patient is fatigued and the doctor will say, ‘Of course you’re fatigued, because you’re sick,’” recalls Raizen. “But that doesn’t say anything about the mechanism of fatigue. And what we’d like to shed light on is this question of why people get fatigued when sick.”

To research this, Raizen, who is associate director of the Chronobiology and Sleep Institute, set out to model this phenomenon in C. elegans, which is a microscopic roundworm that lives on rotted vegetation. The reasons for their use: they reproduce very quickly, have a small number of neurons, and there are plentiful tools to manipulate their genome.

To do this, Hina Sako, a second-year student in the College of Arts & Sciences, was one member of a team of students that conducted a genetics screen. They examined strains of C. elegans determined to have a sleep defect. To conduct the screen, she shocked the roundworms with UV light or heat—equivalents of being sick, for a roundworm—to observe whether they stopped feeding and moving, which are indicators of sleep. Sako then ran further experiments to pinpoint the gene mutation that was disrupting the animals’ sleep.

Sako’s summer research was supported by the Penn Undergraduate Research Mentorship program, as part of the Center for Undergraduate Research & Fellowships. The program provides first- and second-year undergraduates the opportunity to spend a summer conducting research under the guidance of Penn faculty.

“I learned it takes a lot of patience and is a very long process,” Sako says of her research experience.

Her goal is to study either neuroscience or health and societies. She’s taking her first class in the History and Sociology of Science Department this fall. She was interested in a neuroscience project after taking the course “Introduction to Brain and Behavior” in the spring.

“I didn’t learn much about human sleep,” she laughs, reflecting on her experience this summer, “but I did learn a lot about worm sleep.”

“The next step is we want to put together a compendium of all genes that can affect sleep during sickness and once we identify the genes, we want to understand how the genes are acting,” says Raizen. “‘Which brain cells are they acting in?’ ‘What is the order?’ ‘Is this gene acting first and the other genes act in accord, or the other way around? Do they act in parallel?’”

Raizen adds that sleep while sick has been studied in the past mostly in mammals, in which genetic research is far slower and more difficult because of their complex nervous system. The use of roundworms, then, is a new approach.

Raizen says he personally found lab research as an undergraduate to be valuable and tries to make the experience more realistic than what students might be taught in a tightly controlled environment as part of regular course work. He says he also tries to keep some aspects of the project open-ended, so that students can explore their own interests.

“My goal for the students is to, first of all, have fun, but also to learn something and to better understand what we do as scientists,” he says. “And if I’m lucky, one of the students—and I have had a few over the years—stays in science, and that’s been very fulfilling for me.”