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UT Southwestern Medical Center researchers have taken a major steptoward understanding the cellular clock, mapping for the first timethe atomic-level architecture of a key component of the timekeeperthat governs the body's daily rhythms. The daily, or circadian, cycles guided by the body's clocks affectour ability to get a good night's sleep, how fast we recover from jet lag , and even the best time to give cancer treatments, said Dr. Joseph Takahashi, senior author of theScience study published online and a pioneer in the study ofcircadian rhythms. Understanding the structure of the cellular clock could lead tobetter treatments for insomnia , diabetes , and even cancer. "The clock is found in virtually every cell of the body, and isimportant for controlling many different metabolic functions," saidDr. Takahashi, chairman of neuroscience and a Howard Hughes MedicalInstitute (HHMI) investigator at UT Southwestern. Mapping the 3-D structure of the key component in the cellularclock - called the CLOCK:BMAL1 transcriptional activator complex " will have a great impact on the study of circadian rhythms andin other areas like toxicology and the growth of nerve cells, inwhich proteins in the same family play central roles, he said. "Ultimately, we have to go to the atomic level to really understandhow these proteins work" Dr. Takahashi said. The Takahashi laboratory has spent years determining the 3-Dstructure of the CLOCK:BMAL1 complex using X-ray crystallography.The breakthrough came in the spring of 2011 when Yogarany Chelliah,an HHMI research specialist at UT Southwestern, was able tocrystallize the proteins. The structure was determined incollaboration with Dr. Hong Zhang, associate professor ofbiochemistry. The researchers found that the CLOCK protein is tightly wrappedaround the BMAL1 protein in an unusually asymmetrical fashion. Theyidentified three distinct areas for interactions between CLOCK andBMAL1 as well as regions for interactions with other molecules thatmight affect the cellular clock by changing the sleep-wake cycle orother body processes that depend on circadian rhythm, he said. Dr. Takahashi's research on the subject goes back almost 20 years.That's when he began a behavioral study of mice looking for thoseanimals in which their biological clocks seemed out of sync. Afterscreening hundreds of mice, his laboratory in 1994 identified onemutant mouse whose daily cycle was four hours longer than normal.He named that mouse the Clock mutant. Dr. Takahashi then used that mouse to identify the world's firstcircadian rhythm gene in a mammal. Researchers in his laboratorycloned the Clock gene in 1997. In 1998, they discovered that theCLOCK protein worked in concert with the BMAL1 protein in a studydone in collaboration with Dr. Charles Weitz at Harvard MedicalSchool. Two years ago, Dr. Takahashi's team - in collaboration with Dr.Joseph T. Bass at Northwestern University Feinberg School ofMedicine in Chicago - reported in Nature that disruptions in the Clock and Bmal1 genes in mice can alterthe release of insulin by the pancreas, which results in diabetes. "We started on this path a long time ago, and it actually beganwith a mouse, which then allowed us to find the Clock gene, andthen from this gene we now see the proteins from their crystalstructure," Dr. Takahashi said. "For that to all happen after sucha long quest is particularly satisfying." Additional References Citations. I am an expert from ledspotbulb.com, while we provides the quality product, such as China T5 Led Tube Lights , Waterproof Led Strip Lights, T5 Led Tube Lights,and more.
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