New insights on causes of jet lag and shift work disorientation

Timing is everything and our circadian clock, allows us (and almost every other organism on the planet), to predict the daily changes in our environment, such as light and temperature.

The University of Leicester is one of the main UK centres for clock and photoreceptor research, and new findings on the biology of the cryptochrome and light entrainment in the fruitfly (Drosophila melanogaster) by a team of Leicester biologists, led by Dr Ezio Rosato, have made a significant contribution to the field of circadian biology, as reported recently in the August edition of ’Nature Neuroscience’.

One of the most important functions of the circadian clock is its ability to react to and predict environmental cues, light being the most important, keeping the endogenous clock in phase with the external light-dark cycle (entrainment). Cryptochrome is a light-sensitive protein that is the key to entrainment.

Dr Rosato explained the importance of this research: “There are obvious advantages in having a clock. For instance we can start mobilising resources before they are actually needed, or we can temporally separate processes, which would be otherwise incompatible. As the clock evolved long before transcontinental travel and shift work were invented, jet lag and physiological dysfunctions are the price we pay for the unnatural 24-hour society.

“The implications of our frenetic life-style are much more profound than we generally think, as recent studies have indicated that the circadian clock (and clock genes) may be involved in diverse conditions such as tumour suppression, survival of animals with cardiomyopathy heart disease, left ventricular hypertrophy, diabetes, and cocaine sensitisation. It is therefore a very important factor in human and animal health and well-being.”

In fruitflies and mammals the same genes appear to play similar roles in determining how the 24-hour clock works. However, the ease of genetic analysis and the molecular tools available in the fruitfly Drosophila melanogaster, means that progress is particularly rapid with this organism.

The Leicester researchers are interested in a blue-light sensitive protein called CRYPTOCHROME (CRY), which employs light energy for signalling. The main function of CRY in the fly brain is to bring light information directly into the clock mechanism, resetting the time of the endogenous clock in phase with the external light-dark cycle.

The feature in ’Nature Neuroscience’ opens new insights on circadian light signalling and the biology of cryptochromes. The University of Leicester research team showed that by removing the terminal end of CRY (thus creating CRYD), they could generate flies that never ’experience’ night-time, as if they were living in a perpetual Arctic summer. They demonstrated this with a range of behavioural, molecular and cytological experiments.

Dr Rosato commented: “Clearly the CRYD molecule continuously conveys ‘lights on’ signals into the clock, even under constant darkness, drawing a new model of CRY action.

“During our experiments we also noticed that a particular group of neurons were especially affected by the continuous subjective light stimulation. This unprecedented observation allowed us to integrate several threads of circumstantial evidence from previous studies, and implicate this group of neurons as main players in the entrainment of the Drosophila clock.”