Jet lag – the disadvantage of having a clock in the modern world

Air travel challenges our bodies in a way that has never before been encountered in our evolutionary history. It allows us to move rapidly across multiple timezones, quicker than we could have ever moved by foot or animal. Unfortunately, our bodies are unable to adjust quickly enough. We are constrained by our circadian clocks, the things that give our bodies a sense of internal time, which have evolved to coordinate our physiology to the rhythmic and predictable changes in the external environment (as well as other roles) like day and night. The clock keeps its original time when you move timezones like a watch before you’ve reset it. It’s resistant to rapid change, giving us jet lag. However, unlike a watch, the body clock can gradually reset itself over a period of days so that we become tuned to a new local time. Despite this inbuilt mechanism, in an era of global travel it is often too slow.

Is it possible to speed up the resetting process? Can we travel the world without jetlag?

Maybe.
Continue reading “Jet lag – the disadvantage of having a clock in the modern world”

What can a blind cavefish tell us about circadian clocks?

Circadian clocks and a revolving planet go hand-in-hand. But why so many plants and animals have a circadian clock from an evolutionary perspective is relatively unknown. One way to find out is to study animals that live in non-rhythmic environments. And at the end of 2013, my team published a study on exactly that: the circadian clock of the Mexican blind cavefish, Astyanax mexicanus, from data collected in the laboratory and in the fishes’ natural habitat. We showed that these cavefish fish shows wonderful daily patterns of behaviour and gene expression, confirming that it has a functional circadian clock.

Continue reading “What can a blind cavefish tell us about circadian clocks?”

Presentiment – circadian clocks giving plants and animals a sense of time

Presentiment is that long shadow on the lawn
Indicative that suns go down;
The notice to the startled grass
That darkness is about to pass.

Emily Dickinson

Sometimes you find in literature beautiful expressions of technical terms that are otherwise dry and stuffy. Presentiment, by Emily Dickinson, is one of those beautiful expressions. Why did she decide to write a few words about twilight, and at the same time so succinctly summarise one of the key features of the circadian clock? Apparently Dickinson spent much of her adult life withdrawn from the world and, in doing so, she was probably in a position to watch and notice the hidden-in-plain-sight details of the world, such as how the length of shadows allow you to approximate the time of day and how grass may tell time without watches.

Continue reading “Presentiment – circadian clocks giving plants and animals a sense of time”

Circadian clocks in the great outdoors

We’re all aware of our natural body clock pattern: some people are early birds, some people are night owls, a phenomenon known as your chronotype. You can override this with alarm clocks and coffee, which is especially important for shift workers. But have you ever noticed your chronotype shift when you go on holiday, especially when you holiday in the great outdoors?

Researchers from the University of Colorado wondered exactly that and described in 2013 interesting findings on the influence of natural and artificial light on human circadian clocks. Continue reading “Circadian clocks in the great outdoors”

Shifting your clock: shift work and the circadian clock

To many people, the phenomenon known scientifically as the circadian rhythm is bleeding obvious. We sleep in the night and are awake during the day, long-haul flights like those from the UK to Australia gives you jetlag, and night shifts are a right pain in the bum. Detailed explanations involving transcription-translation feedback loops and phase response curves don’t change those facts, they’re a fact of life when we live on a rotating world. But many scientists, myself included, are fascinated in the details, and some scientists, like Céline Vetter and colleagues at the Institute of Medical Psychology at Ludwig-Maximilian-University in Munich, use this eye for detail to find out how we might best cope with our biological timing in a 24-hour society.

Coffee: Are you an early bird or a night owl?

Continue reading “Shifting your clock: shift work and the circadian clock”

What is a circadian clock?

Broadly speaking, the circadian clock is a cell and molecular feedback loop – inside the cell, a bunch of proteins that interact with genes and DNA, which in turn interact back with those original proteins. This cellular feedback loop controls those outward and apparent rhythms we are aware of, like jet lag and waking, as well as many more we may be unfamiliar with, but it isn’t just humans who have a body clock, all life on planet Earth has one, although its workings aren’t exactly the same in all life-forms.

The feedback loop. Proteins join together to activate gene transcription of genes that subsequently repress the original proteins. This feedback generates oscillations of gene expression.
The feedback loop. Proteins join together to activate gene transcription of genes that subsequently repress the original proteins. This feedback generates oscillations of gene expression. From Eckel-Mahan and Sassone-Corsi, 2013, Metabolism and the circadian clock converge.

In animals, the key players are genes called clock, bmal, period and cryptochrome. There are actually multiple versions of the genes, named numerically (clock1a, bmal2, period3 etc) and shortened to 3 or 4 letters (clk1a, bmal2, per3 etc). To explain the cycle, we need to start with clock and bmal and go twice around the feedback loop, each stage showing the effect of the previous.

Firstly, CLOCK and BMAL proteins (CLK and BMAL; by consensus gene names are in italics and PROTEIN names are in uppercase), interact in the cell, joining together to turn on period and cryptochrome genes. As the genes are turned on, they are transcribed by the cell, eventually begetting proteins, PER and CRY proteins. These proteins interact with CLK and BMAL proteins to make CLK and BMAL less activating, repressing CLK and BMAL.

Secondly, as CLK and BMAL are now repressed, the turning on of period and cryptochrome genes is stopped. Fewer PER and CRY proteins are generated by the cell. Fewer PER and CRY proteins means less repression of CLK and BMAL, and so CLK and BMAL are released to begin another cycle.

The overall effect is similar in plants and other organisms: Activator proteins turn on repressor genes, these repressor genes are translated into repressor proteins by the cell and repress the activator proteins and so on. These proteins and genes in the clock aren’t the same in all organisms, but they play similar roles turning on or off genes, modifying the activity of proteins, like how David de Gea and Manuel Neuer are not the same player, but play similar roles for their teams. The fact that clocks have a similar feedback mechanism but consist of different components in the different branches of life adds to the idea that circadian clocks must be evolutionarily adaptive. It is an example of convergent evolution, where two separate species look similar without being evolutionarily related, such as how dolphins and sharks look fairly similar and are adapted to the broadly similar environments but are completely different species. In this case, evolution has dictated that the best body shape for fast and efficient swimming in water is a streamlined oval. In the case of circadian clocks, we can suggest that evolution has dictated that the best way of organising your physiology and behaviour is through the use of a molecular feedback loop which acts within the cells of the body.

 

Two illustrations of how the molecular components make up the circadian clock. On the left - in zebrafish. Clock (CLK) and bmal (BMAL) proteins (there are 6 versions) interact to activate (green arrow) transcription of per and cry genes. PER and CRY proteins then interact with CLK and BMAL to repress (green line with flat on top) their activity. Per and cry are also activated by light. On the right - plants. CCA1 and LHY are the CLK and BMAL equivatlents, interacting to activate PRR7 and PRR9 which then repress CCA1 and LHY.
Two illustrations of how the molecular components make up the circadian clock. On the left – in zebrafish. Clock (CLK) and bmal (BMAL) proteins (there are 6 versions) interact to activate (green arrow) transcription of per and cry genes. PER and CRY proteins then interact with CLK and BMAL to repress (green line with flat on top) their activity. Per and cry are also activated by light. Taken from Vatine et al., 2011, It’s time to swim! Zebrafish and the circadian clock. On the right – plants. CCA1 and LHY are the CLK and BMAL equivatlents, interacting to activate PRR7 and PRR9 which then repress CCA1 and LHY. Taken from Harmer lab at UC Davis