Tuesday, 4 January 2011

SOS: Save our Science - Cryptochrome, lord of time.


 I knew it'd happen sooner or later, I've started falling behind on postings. I'd hoped to put this up on New Year, but that didn't happen. Anyway, Happy New Year to all, hope you all enjoyed yourselves. I've been writing the report on my first project. The first draft is now done. Still a lot to do, and only 1.5 weeks until it's back to work. The next project is all about cytoskeleton and growth in yeast, so a bit different, I'll tell you more once I actually know anything...

So this is a relatively new paper I found, investigating how flies, and possible humans keep track of the time of day and how this is affected by our environment i.e. the sun. It seemed appropriate to do a time piece to see in the new year. Also I'm really excited as this will be my first official Research Blogging post!!

How do you know if it’s day or night? Simple, right? You look at your watch or you look outside. The differences are pretty obvious. But your body actually keeps track of these things itself. Certain proteins in your body keep track of the time of day. This system has been around for billions of years, and is shared between plants and animals.

The subconscious ability to tell night and day depends on circadian rhythms; regular changes in the presence and activity of timekeeper proteins within a part of your brain called the pineal gland (so named because it looks like a pine cone). Experiments have shown that in a room with no clocks and no changes in light levels a human will fall into a roughly 24 hour cycle of sleeping and waking (average 24 hours 11 mins). The average cycle differs between species and in some arctic species appears to be intermittent. Although the cycle is entirely self-sustaining it is trained and altered by light input, modifying it to be more exactly 24 hours long. This involves light sensitive proteins in your eye which signal to the pineal gland.

The pineal gland in the human brain (source)

Jet lag is the result of mismatch between your circadian rhythm and the day-night (light-dark) cycle where you are. It can take several days to correctly alter protein activities to match with your new surroundings and until then you will be sleepy, energetic and hungry at all the wrong times.

Several proteins are unstable in light, so there is less of them during the day. One of these is Cryptochrome, which is sensitive to blue light, it signals to the pineal gland and alters your circadian rhythm to fit with your surroundings. New research, in flies, has uncovered part of the process involved in cryptochrome altering timekeeping.

Studies in plants show that cryptochrome changes its shape in response to light, large alterations in the arrangement of one end of the protein (the C-terminus) allow for cryptochrome to signal by interacting with other proteins. Cryptochrome is often associated with another protein called timeless (TIM), light changes cryptochrome and exposes both cryptochrome and TIM to destruction. The changes in cryptochrome structure are the result of light rearranging electrons in part of the protein structure. Such rearrangements are common in biology and can be induced in many ways, not just by light. Light dependent destruction requires another protein called Jetlag, which tags proteins for destruction. TIM is a key part of your circadian clock, and destroying it resets the clock. The new findings show that even a millisecond of light exposure can alter cryptochrome for upto 30 mins; it is extremely light sensitive. This short exposure is insufficient to alter your internal clock, however.

The structure of cryptochrome in the dark. The atomic detail of the protein is reduced to a ribbon to show how a protein chain folds into a functional shape. The C-terminus is the red tail (front right). (source)
There are many other systems involved in keeping you synchronised with your environment and it is not entirely clear how well this model applies in humans, as the precise activity of cryptochrome between plants and flies is now known to be very different, although the effects are still the same. These systems are involved in jet lag, but may also contribute to severe insomnia and other sleep pattern dysfunctions, so better understanding of our circadian clock has high potential to help the sleeping impaired.

I would be excited to explore circadian rhythms in life forms that have lives independent of the sun, in particular, do deep ocean fish, hydrothermal vent ecosystems and cave dwelling insects maintain their circadian rhythms? Are they still responsive to light? And if not, how to these creatures organise their lives?

Do these tubeworms (Riftia pachyptila) on deep sea vents use the same systems as us to track the days and organise their lives? (source)

The circadian rhythm is a fantastic illustration of evolutionary ingenuity. Somehow we have developed a system that almost perfectly fits with the motions of our planet, tracking a 24 hour rotation on Earth’s axis, biologically speaking this is an arbitrary length of time and circadian rhythm is a brilliant demonstration of adaptation to our environment. It is probably one of the oldest and most conserved mechanisms in life on Earth, possibly one of the first ways we had of responding to the world around us. It is the basis for all time based events; breeding seasons, migrations and hibernations. Perfect synchronisation is essential to much of the life on this planet and is entirely dependent upon this one timekeeper.

Ozturk, N., Selby, C., Annayev, Y., Zhong, D., & Sancar, A. (2010). Reaction mechanism of Drosophila cryptochrome Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1017093108

1 comment:

Genomic Repairman said...

"but it explains how exactly, all the way down to the atomic level, our body keeps track of the time of day"
Remember this is in Drosophila not humans. Not all protein functions are evolutionarily conserved between fruit fly and man. We don't know if this exactly happens in humans yet so tred lightly.

Aziz is a weird dude but his lab does good work.