Dr. John Ewer: The importance of chronobiology in the development of life

Chronobiology is one of the branches of science with greater impact in our lives. Whether gradual or rapid way, our body responds to the course of a series of internal "clocks" that determine a myriad of variables of our physiology.

Humans, other species of animals, plants, and even some bacteria, ordered their biology due to these internal clocks, which enable the physiology of the organism to anticipate the arrival of the day and night. In animals, there is a central clock in the brain that regulates the cycles of sleep and wakefulness; also ordered watches present in the majority of organs, in such a way that the body has a unit for their behavior and Physiology, which is in sync with the planetary cycles of light and darkness.

The laureates of the Nobel Prize in Physiology or medicine 2017, were Jeffrey C. Hall, Michael Rosbash, and Michael Young, who determined the molecular identity of the first so-called "gene clock". After this, they identified other genes involved in the workings of the biological clock, ultimately producing a model for the functioning of the circadian clock that applies to all animals, including humans.

To know more about, and understand the reason for the importance of this milestone, the biology society of Chile spoke with Dr. John Ewer, Professor of the Interdisciplinary Center for neuroscience of Valparaíso (CINV) of the Faculty of Sciences of the University of Valparaiso, who conducts research on biological clocks and his Ph.d. with the Dres. Jeffrey Hall and Michael Rosbash.

What is the importance of these biological clocks?

The certainty about the existence of the biological clocks can be traced back several years; in fact, the first reports date back to 18th century. We now know that the biological clocks are internal mechanisms that allow us to anticipate the arrival of the day; Thus both animals and plants, have the ability to synchronize their activities with the rotation of the Earth.

These skills are the result of the evolution of all life on a planet that has predictable alternations of light and darkness. However, until the date of the award-winning work, it was unknown how could generate a live, a process every day, since the biochemical and neural processes operate at speeds incomparably greater.

How was the work of these scientists after the discovery of the gene clock?

These researchers followed the track of a mutation that affects the cronobiológico system in the research model: flyDrosophila melanogaster. The mutation in the geneperiodIt had isolated during the years ´70s because you specifically alter sleep/wake of fly patterns. In this sense, the researchers managed to isolate a piece of DNA of normal flies that reverted the abnormal phenotype when it was reintroduced in the genome of mutant, which was a feat for the time. In this way, they understood that that piece of DNA containing the geneperiod. However, its sequence did not provide any clue about his identity, nor on the operating mode, since it wasn't a transcription factor or a receiver.

An important clue was to discover that the messenger RNA abundance ofperioddaily changed its abundance and that this did not occur in the mutant lacking functional watch. This led them to propose that the protein produced by the gene somehowperiodIt was necessary for the rhythmic expression of its messenger RNA. A second important clue was the identification of another gene calledtimeless.

The messenger RNA'stimelessalso ciclaba daily and mutations inHe,they were also revoked this cycle. But the most interesting was that mutations intimelessthey eliminated the cycle messenger RNA ofperiod, and vice versa. Or is that to make the clock work, both RNA messengers had to cycle and proteins of both genes were necessary to allow the expression of this rhythm of gene expression. Thus, the first model of the molecular function of a watch, which was generated from alooptranscription/translation directed by genes proteinsperiodandtimeless.

What is this model?

First clarify that this model applies to all animals and plants, so these findings are biologically spectacular. In addition they deliver tools to understand various medical and biological events that are rhythmic. This is how they serve to understand effects physiological and physiopathological of some diseases. They also deliver relevant information at the time of interventions and supply drugs. For example, we know that the effect of a drug varies during the course of the day, so for some drugs can be very important to consider the time when swallowed.

Biologically, it was a remarkable discovery, with impact in areas such as the infectious diseases, nutrition and pharmacology. There are a lot of medical ramifications to his credit.

Differences between the dream and the biological clock

While the clock regulates our sleep-wake rhythms, it is separate from the system that regulates sleep. The latter is essentially a counter of the number of hours we've been awake. In contrast, the clock regulates when you should sleep; for example: individuals of a diurnal species like ours, sleep at night.

In this way, sleep timer in general begins to count in the morning and night, pushing for one to sleep. However, it is possible to stay awake beyond that moment; but must cancel it this sleep deficit, and to do so, the sleep system will force you to sleep during the day, objecting to the indications of the clock.

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Journalist:Patricio Grunert Alarcón. ®
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