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If you want to be awake and alert during the day, you need a good night’s sleep. Sounds straightforward, but the fact is there’s an awful lot we don’t know about the biological significance and functioning of sleep. Even though we spend a good third of our lives in slumber, until now scientists haven’t come up with a persuasive theory. They used to think that sleep helps the body save energy. But it now turns out that we don’t burn many fewer calories while asleep than while awake. “We can only attempt to explain what’s going on,” says Hans Peter Landolt, a sleep researcher at the UZH Institute of Pharmacology and Toxicology.
Landolt is a sleep researcher with a calling who’s been grappling with the topic for years. For the co-head of the Sleep and Health CRRP (see box), the gaps in our knowledge are more of an incentive than a discouragement. In the wake of new findings and methods in molecular genetics, fascinating possibilities are opening up for cracking the secret of sleep, one of the last remaining unsolved riddles in biology. As Landolt explains, with UZH and its clinics representing such a broad spectrum of disciplines, the university is extremely well placed to make new and decisive contributions to this field of knowledge. Sleep research has a long tradition at UZH, not least thanks to Walter Rudolf Hess and his work on the autonomic nervous system back in the 1940s. One upshot of this cluster of research expertise is the recently established Zurich Center for Interdisciplinary Sleep Research (ZiS).
One focus of the Clinical Research Priority Program is the way the body regulates the sleeping-waking cycle. It’s known that both external and internal factors influence the biochemical processes that induce a state of unconsciousness in the body. As a pharmacologist, Landolt is particularly interested in the effects of various biomolecules and their gene variants. These include the sleep-promoting messenger adenosine. Depending on its concentration, the neuromodulator increases the homeostatic sleep pressure, and plays an important role in the sleeping-waking cycle.
One particularly striking feature displayed by some people – the way caffeine affects homeostatic sleep pressure – is directly linked to the adenosine metabolism. Some people can drink a double espresso late at night with no effects at all, while others have to lay off the coffee hours before they go to bed. In 2012 Landolt and his fellow researchers were able to show that this sensitivity is based on gene variants of the adenosine receptor, and is therefore hereditary.
As part of the CCRP, Landolt wants to take research into the stimulant further. “Caffeine has contradictory effects when it comes to type 2 diabetes,” says the pharmacologist. Resistance to insulin, an increasingly widespread phenomenon, is more frequent after subjects drink coffee in the lab, and among people who sleep fewer hours. At the same time, however, epidemiological studies suggest that caffeine protects against diabetes.
Landolt suspects that these contradictory effects also depend on gene variants of adenosine receptors and the degrading enzymes. “We want to understand the molecular genetic basis of these differences and do studies to clarify them,” says the pharmacologist. In other studies Landolt’s group is looking for additional gene variants involved in regulating the sleeping-waking cycle. These include genes of the messengers dopamine and glutamate and their receptors, as well as new genes that have yet to be discovered.
“We’re doing basic research at the interface with clinical practice,” says Landolt. While the primary goal of the clinical research priority program is to develop individualized therapies for people with sleep disorders, the work is bound to bring new insight into the secrets of sleep as well.
