Nav: Home

Dead zones in circadian clocks

May 14, 2019

[Background]

Most organisms on Earth have circadian clocks. In mammals, the circadian pacemaker is located in the suprachiasmatic nucleus (SCN) of the brain. The SCN consists of about 20,000 neurons, and oscillatory gene expression with an approximate 24-hour period can be observed independently in each. These cell-autonomous oscillations of gene expression are controlled by delayed negative feedback regulation of circadian clock genes, and function as a circadian clock to regulate the behavioral and physiological rhythms of organisms.

One of the important properties of circadian clocks is the response to light signals, which enables organisms to become entrained to the 24-hour light-dark cycle on Earth. It has been shown that circadian clocks respond to light signals during the night, whereas they do not respond to such signals during the daytime. This holds true even when an organism is kept in complete darkness; a short light pulse does not change the time of the circadian clock when body time of the individual is at daytime. The time period in which the circadian clock is insensitive to light signals is referred to as the "dead zone". Previous studies have indicated that the presence of a dead zone improves the robustness of the clock. However, the mechanism underlying its generation is unclear.

[Results]

Researchers from Kanazawa University used mathematical modeling and computer simulations to elucidate the mechanism underlying dead-zone generation. Different species have different light-response mechanisms. For example, in the circadian clock system of the fruit fly Drosophila, light signals induce degradation of the circadian repressor protein TIMELESS. In contrast, in mammals, light signals are perceived by the eyes and induce expression of the circadian clock gene Period within the SCN. These differences led researchers from Kanazawa University to question whether the mechanisms for dead-zone generation in these two species are common or distinct.

To address this question, the researchers utilized a mathematical model called the Goodwin Model. This model was used to describe a negative feedback loop in the circadian clock system by considering the concentrations of mRNA and protein as variables. Numerical simulations demonstrated that saturation of transcription of Timeless mRNA induces the generation of a daytime dead zone in the Drosophila circadian clock. In the mammalian circadian clock, saturation of translation, rather than transcription, of PERIOD protein generates a dead zone. Computer simulations demonstrated that saturation of these reactions nullifies the effect of light signals only during the daytime. Thus, saturation of the synthesis of a repressor protein in the negative feedback loop that regulates circadian oscillation may be a conserved mechanism for generating daytime dead zones among different species.

[Significance and future prospects]

The dead zone is considered to be important for robust entrainment of circadian clocks to light-dark cycles. The present study shows that, in principle, even single neurons can realize a dead

zone. This finding suggests that the fundamental properties of circadian clocks are determined at the single-cell level.

Entrainment of the circadian clock to light-dark cycles is fundamental to human health. For example, a mismatch between clock time within the body and the time in a local place can cause jet-lag. Thus, studying the response of the circadian clock to light signals is essential in order to understand one of the most common biological clocks on Earth, which may have medical utility.
-end-


Kanazawa University

Related Circadian Clock Articles:

The discovery of new compounds for acting on the circadian clock
The research team comprised of Designated Associate Professor Tsuyoshi Hirota and Postdoctoral Fellows Simon Miller and Yoshiki Aikawa, of the Nagoya University Institute of Transformative Bio-Molecules, has succeeded in the discovery of novel compounds to lengthen the period of the circadian clock, and has shed light on their mechanisms of action.
Let there be 'circadian' light
Researchers publishing in Current Biology describe the science behind creating lighting to make us all happy and productive indoors.
U of M research discovers link between stress and circadian clock health
New research from the University of Minnesota Medical School found a little stress can make the circadian clock run better and faster.
The role of GABA neurons in the central circadian clock has been discovered
Temporal order of physiology and behavior is regulated by the central circadian clock located in the SCN.
Researchers take aim at circadian clock in deadly brain cancer
Scientists at USC and UC San Diego have discovered a potential novel target for treating glioblastoma, the deadly brain cancer that took the life of Sen.
Circadian clock and fat metabolism linked through newly discovered mechanism
Princeton University researchers found that the enzyme Nocturnin, known for its role in fat metabolism and circadian rhythm, acts on two well-established molecules in metabolism.
Dead zones in circadian clocks
Circadian clocks of organisms respond to light signals during night but do not respond in daytime.
Circadian clock plays unexpected role in neurodegenerative diseases
Northwestern University researchers induced jet lag in a fruit fly model of Huntington disease and found that jet lag protected the flies' neurons.
Researchers locate circadian clock that controls daily rhythms of aggression
Synchronized by light and darkness, the circadian clock exerts control over wake/sleep cycles, body temperature, digestion, hormonal cycles and some behavior patterns.
The rhythm of genes: How the circadian clock regulates 3-D chromatin structure
EPFL biologists and geneticists have uncovered how the circadian clock orchestrates the 24-hour cycle of gene expression by regulating the structure of chromatin, the tightly wound DNA-protein complex of the cell.
More Circadian Clock News and Circadian Clock Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.