Resetting Your Biological Clock
Posted by Lauren Rugani on May 1, 2009
It’s Friday, and most of us probably can’t wait for the weekend to be able to sleep in. We justify shunning our alarm clocks by saying that we need to “catch up” on sleep in a futile attempt to awake refreshed on Monday morning. But often our personal and professional schedules don’t coincide with our natural circadian rhythms (our internal biological clocks) so we constantly have to retrain our bodies. Someday, however, there could be a simple drug that will reset our circadian clocks for us. In an important preliminary step toward this goal, Scripps researchers have modeled the 3-D structures of the proteins that control our master timepieces.
Circadian rhythms in humans follow a rough 24-hour cycle that corresponds to the natural light/dark cycle on Earth. The body translates environmental cues like sunlight or temperature into vital bodily processes like sleep and digestion (though not necessarily respectively). People also have the ability to alter their circadian clock so that it follows a consistent pattern in the absence of natural factors – such as those who work the night shift or frequently travel across time zones. One of the key players involved in human circadian rhythms are proteins called cryptochromes, which respond to blue light to generate and maintain daily schedules. Observing the structure of these proteins will help scientists to better understand their function, but to date it has been nearly impossible to do so because the cells don’t stay in a stable state.
So the Scripps group turned to a close relative of cryptochromes – plant proteins called photolyases that repair DNA that is damaged by ultraviolet rays in sunlight. Although the two proteins have different roles, they have the same structure and require the same chemical compounds to become activated, so modeling the plant protein would give good insight into the role of human cryptochromes.
They moved the plant gene that produces photolyase enzymes into E. coli bacteria cells to create a lot of the protein. The proteins were then crystallized, or prodded into an organized, repeating pattern, and then observed by a process called x-ray diffraction that allowed the team to observe the three dimensional structure of the protein. They also created many mutant variations of the protein to study exactly how the structure affects its function. They found an amino acid sequence that affects the length of the circadian rhythm, and want to look into the various interactions of the cryptochrome proteins.
Aside from remedying night owls and jet lag sufferers, understanding the mechanisms behind the circadian clock could also help treat or cure related disorders such as delayed or advanced sleep phase syndromes. Sounds like good news for perpetual insomniacs like me.