Cool Image: A Circadian Circuit

Clock neurons (middle right, right corner and edge), leucokinin (LK) neurons (top left, top right and bottom middle), leucokinin receptor (LK-R) neurons (top left, top right and bottom middle)

This image, taken with a confocal microscope, shows how time-of-day information flows through the fruit fly brain. Clock neurons (stained in blue) communicate with leucokinin (LK) neurons (stained in red at the top left, top right and bottom middle), which, in turn, signal to leucokinin receptor (LK-R) neurons (stained in green). This circuit helps regulate daily activity in the fly. Credit: Matthieu Cavey and Justin Blau, New York University.

Feeling sleepy and dazed after the switch to daylight savings time this weekend? Your internal clocks are probably a little off and need some time to adjust.

Researchers have been studying biological clocks for decades to figure out how they control circadian rhythms, the natural 24-hour pattern of physical, mental and behavioral changes that affect sleep, appetite and metabolism. Knowing more about what makes our clocks tick could help researchers develop better therapies for sleep problems, metabolic conditions and other disorders associated with mistimed internal clocks. Continue reading

Turning Back Every Clock

Clock
Scientists are studying which genes control biological clock gears and which genes are controlled by them. Credit: Stock image.

When daylight savings time ends this Sunday, we’ll need to adjust every clock in our homes, cars and offices. Our internal clocks will need to adjust too.

The body has a master clock in the brain, as well as others in nearly every tissue and organ. These biological clocks drive circadian rhythms, the physical, mental and behavioral changes we experience on a roughly 24-hour cycle. Your hunger in the morning and sleepiness at night, for example, are caused partly by clock gears in motion. These gears can get out of synch with the day-night cycle when the time changes or when we travel through time zones.

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Scientists Shine Light on What Triggers REM Sleep

Illustration of a brain.

While studying how the brain controls REM sleep, researchers focused on areas abbreviated LDT and PPT in the mouse brainstem. This illustration shows where these two areas are located in the human brain. Credit: Wikimedia Commons. View larger image

Has the “spring forward” time change left you feeling drowsy? While researchers can’t give you back your lost ZZZs, they are unraveling a long-standing mystery about sleep. Their work will advance the scientific understanding of the process and could improve ways to foster natural sleep patterns in people with sleep disorders.

Working at Massachusetts General Hospital and MIT, Christa Van Dort Exit icon, Matthew Wilson Exit icon and Emery Brown Exit icon focused on the stage of sleep known as REM. Our most vivid dreams occur during this period, as do rapid eye movements, for which the state is named. Many scientists also believe REM is crucial for learning and memory.

REM occurs several times throughout the night, interspersed with other sleep states collectively called non-REM sleep. Although REM is clearly necessary—it occurs in all land mammals and birds—researchers don’t really know why. They also don’t understand how the brain turns REM on and off. Continue reading

4 Timely Facts About Our Biological Clocks

Illustration of circadian rhythm.
Genes and proteins run biological clocks that help keep daily rhythms in synch. Credit: Wikimedia Commons. View larger image

After you roll your clocks back by an hour this Sunday, you may feel tired. That’s because our bodies—more specifically, our circadian rhythms—need a little time to adjust. These daily cycles are run by a network of tiny, coordinated biological clocks.

NIGMS’ Mike Sesma tracks circadian rhythm research being conducted in labs across the country, and he shares a few timely details about our internal clocks:

1. They’re incredibly intricate.

Biological clocks are composed of genes and proteins that operate in a feedback loop. Clock genes contain instructions for making clock proteins, whose levels rise and fall in a regular cyclic pattern. This pattern in turn regulates the activity of the genes. Many of the results from circadian rhythm research this year have uncovered more parts of the molecular machinery that fine-tune the clock. Earlier in the month, we blogged about an RNA molecule that cues the internal clock.

2. Every organism has them—from algae to zebras.

Many of the clock genes and proteins are similar across species, allowing researchers to make important findings about human circadian processes by studying the clock components of organisms like fruit flies, bread mold and plants.

3. Whether we’re awake or asleep, our clocks keep ticking.

While they might get temporarily thrown off by changes in light or temperature, our clocks usually can reset themselves.

4. Nearly everything about how our body works is tied to biological clocks.

Our clocks influence alertness, hunger, metabolism, fertility, mood and other physiological conditions. For this reason, clock dysfunction is associated with various disorders, including insomnia, diabetes and depression. Even drug efficacy has been linked to our clocks: Studies have shown that some drugs might be more effective if given earlier in the day.

Learn more:
Circadian Rhythms Fact Sheet
Resetting Our Clocks: New Details About How the Body Tells Time Article from Inside Life Science

An RNA Molecule That Cues the Internal Clock

Clock
Dysfunction in our internal clocks may lead to insufficient sleep, which has been linked to an increased risk for chronic diseases. Credit: Stock image.

Our internal clocks tell us when to sleep and when to eat. Because they are sensitive to changes in daytime and nighttime cues, they can get thrown off by activities like traveling across time zones or working the late shift. Dysfunction in our internal clocks may lead to insufficient sleep, which has been linked to an increased risk for chronic diseases like high blood pressure, diabetes, depression and cancer.

Researchers led by Yi Liu Exit icon of the University of Texas Southwestern Medical Center have uncovered a previously unknown mechanism by which internal clocks run and are tuned to light cues. Using the model organism Neurospora crassa (a.k.a., bread mold), the scientists identified a type of RNA molecule called long non-coding RNA (lncRNA) that helps wind the internal clock by regulating how genes are expressed. When it’s produced, the lncRNA identified by Liu and his colleagues blocks a gene that makes a specific clock protein.

This inhibition works the other way, too: The production of the clock protein blocks the production of the lncRNA. This rhythmic gene expression helps the body stay tuned to whether it’s day or night.

The researchers suggest that a similar mechanism likely exists in the internal clocks of other organisms, including mammals. They also think that lncRNA-protein pairs may contribute to the regulation of other biologic processes.

Learn more:
University of Texas Southwestern Medical Center News Release Exit icon
Circadian Rhythms Fact Sheet
Resetting Our Clocks: New Details About How the Body Tells Time Article from Inside Life Science
Remarkable RNAs Article from Inside Life Science

Resetting Our Clocks: New Details About How the Body Tells Time

VIP in time-keeping brain cells
Boosting doses of a molecule called VIP (green) in time-keeping brain cells (blue) helped mice adjust quickly to major shifts in light-dark cycles. Credit: Cristina Mazuski in the lab of Erik Herzog, Washington University in St. Louis.

Springing clocks forward by an hour this Sunday, traveling across time zones, staring at a computer screen late at night or working the third shift are just a few examples of activities that can disrupt our daily, or circadian, rhythms. These roughly 24-hour cycles influence our physiology and behavior, and they’re driven by our body’s network of tiny timekeepers. If our daily routines fall out of sync with our body clocks, sleep, metabolic and other disorders can result.

Researchers funded by the National Institutes of Health have spent decades piecing together the molecular mechanisms of our biological clocks. Now, they’re building on that basic knowledge to better understand the intricate relationship among these clocks, circadian rhythms and physiology—and ultimately, find ways to manipulate the moving parts to improve our modern-day lives.

Continue reading this new Inside Life Science article

Stop the (Biological) Clock

Molecular structure of the three proteins in blue-green algae’s circadian clock.  Credit: Johnson Lab, Vanderbilt University.
Molecular structure of the three proteins in blue-green algae’s circadian clock. Credit: Johnson Lab, Vanderbilt University.

Many microorganisms can sense whether it’s day or night and adjust their activity accordingly. In tiny blue-green algae, the “quartz-crystal” of the time-keeping circadian clock consists of only three proteins, making it the simplest clock found in nature. Researchers led by Carl Johnson of Vanderbilt University recently found that, by manipulating these clock proteins, they could lock the algae into continuously expressing its daytime genes, even during the nighttime.

Why would one want algae to act like it’s always daytime? The kind used in Johnson’s study is widely harnessed to produce commercial products, from drugs to biofuels. But even when grown in constant light, algae with a normal circadian clock typically decrease production of biomolecules when nighttime genes are expressed. When the researchers grew the algae with the daytime genes locked “on” in constant light, the microorganism’s output increased by as much as 700 percent. This proof of concept experiment may be applicable to improving the commercial production of compounds such as insulin and some anti-cancer drugs.

Learn more:

Vanderbilt University Press Release Exit icon
Johnson Laboratory Exit icon
Circadian Rhythms Fact Sheet
The Rhythms of Life Article from Inside Life Science

Cool Image: Tick Tock, Master Clock

Master clock in mouse brain with the nuclei of the clock cells shown in blue and the VIP molecule shown in green. Credit: Cristina Mazuski in the lab of Erik Herzog, Washington University in St. Louis.

Master clock in mouse brain with the nuclei of the clock cells shown in blue and the VIP molecule shown in green. Credit: Cristina Mazuski in the lab of Erik Herzog, Washington University in St. Louis.

Our biological clocks play a large part in influencing our sleep patterns, hormone levels, body temperature and appetite. A small molecule called VIP, shown in green, enables time-keeping neurons in the brain’s central clock to coordinate daily rhythms. New research shows that, at least in mice, higher doses of the molecule can cause neurons to get out of synch. By desynchronizing mouse neurons with an extra burst of VIP, Erik Herzog Exit icon of Washington University in St. Louis found that the cells could better adapt to abrupt changes in light (day)-dark (night) cycles. The finding could one day lead to a method to reduce jet lag recovery times and help shift workers better adjust to schedule changes.

Learn more:

Washington University in St. Louis News Release Exit icon
Circadian Rhythms Fact Sheet
Tick Tock: New Clues About Biological Clocks and Health Article from Inside Life Science
A Light on Life’s Rhythms Article from Findings Magazine