Circadian rhythms — the natural cycle that dictates our biological processes over a 24-hour day — does more than tell us when to sleep or wake. Disruptions in the cycle are also associated with depression, problems with weight control, jet lag and more. Now Prof. Yoav Gothilf of Tel Aviv University's Department of Neurobiology at the George S. Wise Faculty of Life Sciences is looking to the common zebrafish to learn more about how the human circadian system functions.
Prof. Gothilf and his Ph.D. student Gad Vatine, in collaboration with Prof. Nicholas Foulkes of the Karlsruhe Institute for Technology in Germany and Dr. David Klein of the National Institute of Health in Maryland, has discovered that a mechanism that regulates the circadian system in zebrafish also has a hand in running its human counterpart.
The zebrafish discovery provides an excellent model for research that may help to develop new treatments for human ailments such as mental illness, metabolic diseases or sleep disorders. The research appears in the journals PLoS Biology and FEBS Letters.
A miniature model
Zebrafish may be small, but their circadian system is similar to those of human beings. And as test subjects, says Prof. Gothilf, zebrafish also have several distinct advantages: their embryos are transparent, allowing researchers to watch as they develop; their genetics can be easily manipulated; and their development is quick — eggs hatch in two days and the fish become sexually mature at three months old.
Previous research on zebrafish revealed that a gene called Period2, also present in humans, is associated with the fish's circadian system and is activated by light. "When we knocked down the gene in our zebrafish models," says Prof. Gothilf, "the circadian system was lost." This identified the importance of the gene to the system, but the researchers had yet to discover how light triggered gene activity.
The team subsequently identified a region called LRM (Light Responsive Model) within Period2 that explains the phenomenon. Within this region, there are short genetic sequences called Ebox, which mediate clock activity, and Dbox, which confer light-driven expression — the interplay between the two sequences is responsible for light activation. Based on this information, they identified the proteins which bind the Ebox and Dbox and trigger the light-induction of the Period2 gene, a process that is important for synchronization of the circadian system.
To determine whether a similar mechanism may exist in humans, Prof. Gothilf and his fellow researchers isolated and tested the human LRM and inserted it into zebrafish cells. In these fish cells, the human LRM behaved in exactly the same way, activating Period2 when exposed to light — and unveiling a fascinating connection between humans and the two-inch-long fish.
Shedding new light on circadian systems and the brain
Zebrafish and humans could have much more in common, Prof. Gothilf says, leading to breakthroughs in human medicine. Unlike rats and mice but like human beings, zebrafish are diurnal — awake during the day and asleep at night — and they have circadian systems that are active as early as two days after fertilization. This provides an opportunity to manipulate the circadian clock, testing different therapies and medications to advance our understanding of the circadian system and how disruptions, whether caused by biology or lifestyle, can best be treated.
Prof. Gothilf believes this model has further application to brain and biomedical research. Researchers can already manipulate the genetic makeup of zebrafish, for example, to make specific neurons and their synapses (the junctions between neurons in the brain) fluorescent — easy to see and track. "Synapses can be actually counted. This kind of accessible model can be used in research into degenerative brain disorders," he notes, adding that several additional research groups at TAU are now using zebrafish to advance their work.
George Hunka | EurekAlert!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy