Sleeping With the (Zebra) Fishes

People can reject food and control their thirst, but we cannot keep from falling asleep. Even though we spend a third of our lives asleep and treat the prevalence of sleep disorders, we know remarkably little about why we sleep or how sleep is regulated.

On February 22, at 8 p.m. in Beckman Auditorium, Caltech assistant professor of biology David Prober will discuss his lab’s efforts to find new approaches to answer these questions and the discoveries they’ve made using the zebrafish as a simple animal model—discoveries that may have implications for our understanding of sleep in humans as well. Admission is free.

What do you do?
My lab studies how genes and neurons regulate sleep. Most sleep research is performed using laboratory mice. We are taking a different approach by using zebrafish, a small tropical fish that can be found in pet stores and has recently emerged as a powerful animal model for exploring many questions in biology. Zebrafish have several advantages for studying sleep, including a brain that is anatomically similar to ours but much simpler, optical transparency that allows us to monitor the activity of neurons throughout the brain while the animals are awake or asleep, and a small size that enables large-scale experiments. Zebrafish also have a diurnal sleep/wake pattern similar to that of humans and unlike the nocturnal mice that are commonly used for sleep research. As a result, zebrafish are, in some ways, a better animal model than mice to explore how sleep is regulated in humans.

Why is this important?
We spend a third of our lives asleep, and sleeplike behaviors have been observed across the animal kingdom, including in animals as simple as jellyfish. These observations suggest that sleep serves an ancient and essential function, but we don’t know what this function is or how sleep is regulated. These questions are medically relevant because sleep disorders are common, but few effective therapies are available. Beyond a basic desire to understand this biological mystery, we hope that determining how sleep is regulated will lead to novel therapies for sleep disorders and may also provide clues as to the function of sleep.

How did you get into this line of work?
Our work is inspired by [late professor emeritus] Seymour Benzer, whose seminal research showing that genes can regulate complex behaviors in fruit flies was performed in the space that my lab now occupies at Caltech. After studying genetic mechanisms that underlie cancer for my PhD, I wanted to change fields and focus on a significant and long-standing question that I knew would keep me busy for many years. After considering several avenues of research, I kept coming back to sleep as one of the last great mysteries of biology and one that has proved to be relatively intractable to solving. It’s amazing that, despite decades of intense research, we still have a poor understanding of why we sleep or how sleep is regulated. When we began this work, the zebrafish had just started to be used to ask how genes and neurons regulate a variety of behaviors, so using zebrafish to address mechanisms that underlie sleep was an exciting, albeit risky, undertaking. Fortunately, this approach has proved to be fruitful and has allowed us to address long-standing questions in the sleep field.