Featured Research

from universities, journals, and other organizations

New Research Shows How Proteins Make Biological Clock Tick

Date:
January 14, 2006
Source:
Rockefeller University
Summary:
Just as a pocket watch requires a complex system of gears and springs to keep it ticking precisely, individual cells have a network of proteins and genes that maintain their own internal clock — a daily rhythm that, in humans, regulates metabolism, cell division and hormone production, as well as the wake-sleep cycle. Studying this “circadian” rhythm in fruit flies, which have genes that are homologous to our own, scientists have constructed a basic model of how the cellular timekeeper works. But now, a new report in this week’s issue of Science turns the old model on its head.

Just as a pocket watch requires a complex system of gears and springs to keep it ticking precisely, individual cells have a network of proteins and genes that maintain their own internal clock — a daily rhythm that, in humans, regulates metabolism, cell division and hormone production, as well as the wake-sleep cycle. Studying this “circadian” rhythm in fruit flies, which have genes that are homologous to our own, scientists have constructed a basic model of how the cellular timekeeper works. But now, a new report in this week’s issue of Science turns the old model on its head: By providing a glimpse into living cells, Rockefeller University researchers have uncovered a previously undetected clock inside the circadian clock.

Related Articles


At the most basic level, an organism’s sleep-wake rhythms are governed by 10 known genes. In the fly, two of those genes — period and timeless — produce proteins that fluctuate in a negative feedback loop that takes about 24 hours to complete. At night, two other genes (clock and cycle) stimulate production of Period and Timeless proteins, which begin to accumulate in the cell’s cytoplasm. After about six hours, the two proteins move into the nucleus; their presence there turns off the genes, which then remain inactive until Period and Timeless degrade and the whole cycle begins anew.

Michael Young, the Richard and Jeanne Fisher Professor at Rockefeller University and head of the Laboratory of Genetics, isolated period, the first circadian gene, in 1984. He and his peers have been piecing together the cellular circadian puzzle ever since, and thought they had some of the basics figured out. Prior studies, which examined the placement of Period and Timeless during different stages of the cycle, seemed to indicate that the two proteins idle in a cell’s cytoplasm until they bump into each other and then, bound together, enter the nucleus. But Young and Pablo Meyer, who was then a graduate student in Young’s lab, used a novel method to show that this scenario was far too simple.

Meyer, a physicist by training, found himself frustrated by how little he could see of what was occurring in a cell. “The truth is, we really don’t know, mechanistically, what happens in the cytoplasm, and how things are being done in such a precise way,” Meyer says. So he turned to a technique invented in 1948, called Fluorescence Resonance Energy Transfer. FRET gauges interactions between proteins by fluorescently tagging them and measuring how they react to different wavelengths of light. But the technique is complicated and no one had ever thought to use it to follow proteins in a single cell for an extended period of time.

“This begins to measure all these biochemical interactions inside the cell,” Meyer says. For the first time, Period and Timeless could be tracked within a cell for eight hours or longer. “No one had ever labeled the components to follow them over time, to see one clock as it ticks away in a single cell,” Young says. “All the biochemistry and molecular biology that had been done on this had been piecing together information from dead flies.” Now, instead of freeze-frames, they had a movie. (See image at right.)

The movie allowed them to follow the interactions between Period and Timeless with a resolution never before possible. They discovered that, rather than randomly colliding, the two proteins bind together in the cytoplasm almost immediately and create what Young and Meyer refer to as an “interval timer.” Then, six hours after coming together, the complexes rapidly break apart and the proteins move into the nucleus singly, all of them within minutes of each other. “Some switch is thrown at six hours that lets the complex explode. The proteins pop apart and roll into the nucleus,” Young says. “Somehow, implanted within the system is a timer, formed by Period and Timeless, that counts off six hours. You have a clock within a clock.” He notes that this precise timer shows how carefully orchestrated interactions between proteins really are.

He and Meyer, who is about to begin his postdoctoral research at Columbia University, have yet to figure out exactly how the timer works, but its discovery opens up the door to a whole new suite of questions. “How does this interval timer tick? Is it made from additional proteins? Is this the only such timer in the circadian clock? Each of these questions are ahead of us,” Young says. “A couple of years ago, we had identified lots of genes and had this sweeping picture of how circadian clocks work. But this indicates that there are much more formidable properties of the system that were overlooked.”


Story Source:

The above story is based on materials provided by Rockefeller University. Note: Materials may be edited for content and length.


Cite This Page:

Rockefeller University. "New Research Shows How Proteins Make Biological Clock Tick." ScienceDaily. ScienceDaily, 14 January 2006. <www.sciencedaily.com/releases/2006/01/060114152445.htm>.
Rockefeller University. (2006, January 14). New Research Shows How Proteins Make Biological Clock Tick. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2006/01/060114152445.htm
Rockefeller University. "New Research Shows How Proteins Make Biological Clock Tick." ScienceDaily. www.sciencedaily.com/releases/2006/01/060114152445.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Dinosaur Species Found in Museum Collection

New Dinosaur Species Found in Museum Collection

Reuters - Innovations Video Online (Nov. 27, 2014) A British palaeontologist has discovered a new species of dinosaur while studying fossils in a Canadian museum. Pentaceratops aquilonius was related to Triceratops and lived at the end of the Cretaceous Period, around 75 million years ago. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Classic Hollywood Memorabilia Goes Under the Hammer

Classic Hollywood Memorabilia Goes Under the Hammer

Reuters - Entertainment Video Online (Nov. 26, 2014) The iconic piano from "Casablanca" and the Cowardly Lion suit from "The Wizard of Oz" fetch millions at auction. Sara Hemrajani reports. Video provided by Reuters
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins