Although sleep is a behavior common to many kinds of animals, we still know nothing about the functions and regulation of sleep. Uncovering the mechanisms of sleep will pave the way to fundamental treatments for sleep disorders such as insomnia and sleep apnea syndrome.

Professor YANAGISAWA Masashi, Director of the International Institute for Integrative Sleep Medicine

■ The many mysteries of sleep

Sleep is a reversible process in which healthy individuals lose consciousness and suspend activity. This kind of behavior is observed not only in mammals and birds, but also in fish, reptiles, and insects. A sleeping animal is completely unproductive and unable to find food or protect itself. Although it would seem beneficial from an evolutionary perspective not to adopt this kind of extremely risky behavior, there is no species that does not sleep. This must mean that animals somehow benefit from losing consciousness for hours a day to a degree that exceeds the great risk. To give one example, a person might be unable to play something on an instrument after practicing for hours one day, but can do it the next day after one night of sleep. Everyone has experienced something like that before, and sleep is known to be somehow involved in boosting the ability to memorize knowledge, skills, occurrences, and others. However, we have absolutely no understanding of the role that sleep plays as a behavior common to all animals.

Regulation of sleepiness, sleep quantity, and sleep depth is also a complete mystery. We get sleepy when we do not sleep, and even if we get a lot of sleep we go back to sleep at almost the same time every day. On the other hand, sleepiness can also disappear temporarily in states of emergency or excitement. These kinds of homeostatic, circadian, and affective regulations on sleep are well known as superficial phenomena, but we still do not know anything about their expression in the brain.

■ The discovery of orexin and sleep research
Prof. Yanagisawa began to pursue sleep research after his discovery of a neurotransmitter called orexin. At that time, absolutely nothing was known about the function of orexin. Eventually, it was discovered that mice that cannot produce orexin develop a sleep disorder called narcolepsy, which showed that the ability to switch between sleeping and waking can be disrupted by an abnormality in a single gene. This was a major advance in sleep science.

Poor sleep not only affects activity the following day, but also increases risk of medical conditions such as hypertension and stroke. In addition, sleep disorders often appear as an important sign of conditions such as depression and Alzheimer's disease. Many people suffer from insomnia and the number of doctors specialized in sleep is increasing, but treatment almost always consists of palliative approaches such as sleeping pills or lifestyle counseling. If we understood the mechanisms of sleep, we could develop new types of sleeping pills that do not cause side effects or dependency issues, which would enable treatment of various diseases by broadening the medical treatment options for sleep disorders.

■ The world's first research center for basic research on sleep

The International Institute for Integrative Sleep Medicine, newly built at the University of Tsukuba at the end of 2012 after selection by the Ministry of Education, Culture, Sports, Science and Technology for the World Premier International Research Center (WPI) program, is the world's first research center for basic research on sleep. The Center has gathered distinguished researchers from all over the world, making an active effort to also incorporate fields such as chemistry, biology, and drug discovery, to enable academic research integrated with the medical field. The ultimate plan is to have nearly 200 researchers and staff members in total.

Center staff are also striving to build new unconventional systems for administrative and HR processes that do not follow traditional university rules. It already has a flat organizational structure where the number of faculty members and compensation are not determined by rank.

■ Edging closer to solving the mysteries of sleep
Research studies exploring sleep mechanisms have no hypotheses. This is because we are so clueless about this area of science that it is not even possible to form a hypothesis. Therefore, the only approach that can be used is to rely on the assumption that sleep is regulated genetically and patiently perform comprehensive screening of genes using a research method called forward genetics. The first step in this process is to create mutants with sleep abnormalities. Large numbers of mice with randomly generated mutations are created, individuals with sleep disorders are identified, and the causative genes are located. This can be a daunting task because only about one mouse in several thousand will develop such a mutation. However, each discovery that is made has the potential to be a stepping stone to more and more new discoveries.

Nevertheless, it takes very brave researchers to do this kind of screening research in practice. Researchers may go several years without seeing any results, and the research costs both money and manpower. That is why the special WPI designation was such a great opportunity. Although responding to critical evaluation of research results is a huge responsibility, Prof. Yanagisawa has the sense that he is edging ever closer to uncovering the mysteries of sleep all at once and is eagerly anticipating that day. The obscurity surrounding this topic is the greatest appeal of sleep research today.

Article by Science Communicator at the Office of Public Relations