Nav: Home

New research helps to explain how temperature shifts the circadian clock

December 01, 2015

For many living things, a roughly 24-hour internal clock governs the rhythms of life -- everything from sleep in animals, to leaf opening in plants and reproduction in bread mold. Scientists have come to understand much about this internal time-keeping system, but one important aspect, its complex response to temperature, remains enigmatic.

The reason is that while warming and cooling cause the clock to shift forward or backward, they cannot shorten or lengthen its 24-hour cycle. New research, published Nov. 2, 2015 in the Proceedings of the National Academy of Sciences, explores how this is possible.

"Our research suggests an explanation: The internal gears within the clock -- the cyclical activity of genes and concentrations of proteins -- do not change with temperature, so the length of the cycle stays the same," says senior author Eric Siggia, Viola Ward Brinning and Elbert Calhoun Brinning Professor at Rockefeller's Center for Studies in Physics and Biology.

"Meanwhile, the core mechanisms of the clock appear to be linked to external pathways that are sensitive to temperature. This external coupling can cue the clock to skip ahead or backward," Siggia says.

This study is the result of a collaboration between Siggia's lab and Michael W. Young's Laboratory of Genetics. It builds upon growing evidence calling into question a model that has, for decades, been used to explain temperature-induced shifts.

A new explanation

In recent decades, researchers have uncovered the genetic processes that drive the clocks of many different species. In fruit flies, for example, a pair of proteins called Period and Timeless are transcribed from their genes, and after a series of steps, eventually repress their own production. This cycle takes approximately 24 hours, regardless of the temperature at which an organism lives. This makes the circadian clock an oddity, since temperature alters the rate at which most biological processes take place.

For decades, the dominant explanation for 24-hour period's independence from temperature, a phenomenon known as temperature compensation, relied on the heat-sensitivity of the chemical reactions that run the time-keeping cycle. According to this theory, the effects of temperature on the many chemical reactions in the circadian cycle cancel each other out, leaving the period unaffected by changes in temperature.

But increasingly, studies have suggested something else is going on. For example, a 2010 study showed that in fruit flies whose protective heat and stress response has been inhibited, the clock hardly shifts with temperature changes. Since the conventional model predicts that everything is temperature sensitive, no single pathway should be this influential.

Previous work in Siggia's lab suggested an alternative explanation. The investigators used computational tools to simulate the evolution of gene networks, including a model of the circadian clock. Their findings suggested that temperature-induced shifts of the clock involve genetic pathways separate from the molecular cycles at the core of the clock, but linked to them, and that the core clock is actually insensitive to temperature.

Proportional at different temperatures

The recent study's lead author, Philip Kidd, a postdoc in the labs of Siggia and Young, set out to test this hypothesis. Using a conceptual model and molecular experiments in flies, he examined how the oscillations of individual components of the clock, such as concentrations of the protein Timeless, changed with temperature.

"If our prediction is correct, and the core mechanism of the clock does not respond to temperature, then the fluctuations in a particular component at different temperatures should remain proportional to one another--that is, we should be able to rescale them so they align," Kidd says. "And when we examined the transcription rate of Timeless, as well as its subsequent levels at three temperatures, that was precisely what we found."

Meanwhile, in a fly with a mutation that allows the length of the clock's period to change with temperature, the curves describing fluctuations in Timeless at the three temperatures shifted around and changed shapes, and were no longer proportional, confirming the premise of Siggia's earlier model.

"The mechanism by which the clock can partially ignore temperature has remained a key problem for those of us seeking to understand how it functions. Our work, and that of others, points to a general system that could explain this mystery and lead to a comprehensive understanding of these clocks," says Young, a study co-author and the Richard and Jeanne Fisher Professor.
-end-


Rockefeller 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.