Invited resubmission: the Drosophila circadian clock under simulated natural conditions

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Like humans, the fruitfly, Drosophila melanogaster, has an internal 24 hour clock that times its behaviour and physiology. The genetic basis for this clock is practically the same for both organisms, which also have dedicated neurons in the brain in which these clock genes are expressed. These neurons generate rhythmic signals that are transmitted to other regions of the brain and serve to generate rhythmic behaviour. These similarities between humans and flies means that the latter serve as a cheap and convenient model system for studying the molecular neurobiology of clocks. As clocks are important for human health and well-being (consider chronic shift workers, who have higher levels of health-related problems than the general population), clock research in flies has significant medical relevance. Much of what we know about the fly clock has been collected in artificial laboratory environments at constant warm temperatures, usually in 12 hours of light followed by 12 hours of darkness, or in constant light or constant dark. While it is necessary to simplify the complex natural environment, we also run the risk of misunderstanding how clocks might work in nature. We have spent more than three years studying fly locomotor rhythms in the wild, and our results suggest that some of our cherished concepts about the fly clock, might need some serious revision. However, we cannot expect our colleagues to go through the pain of studying fly behaviour in the wild, as it is very inconvenient, difficult, and unpredictable in terms of the elements, which have us at their mercy. Thus, we need to simulate natural conditions in the laboratory, and this is what our proposal is about. We have amassed an enormous amount of field data on fly behaviour, for different fly strains, clock mutants, as well as associated meteorological observations, but we need to realistically mimic any kind of day, hot, cold, bright, overcast, with moonlight, without, in any season. In order to do this, we have developed a simulated programmable light-source which can mimic the natural light cycle in almost any environmental situation, including moonlight, twilights, and the daily changes in the spectrum. This is placed in a programmable incubator that can similarly simulate any environmental temperature cycle. In preliminary studies we have shown that we can routinely replicate almost all of the unexpected findings we have recorded in the wild, so we know our simulations are realistic. We now have an unique opportunity to study a complex behaviour in a quasi-natural setting and we can now attempt to systematically dissect and manipulate the clock, behaviourally, genetically, and neurobiologically, using the sophisticated fly-specific tools we have at our disposal, and understand more completely how natural environmental signals tune up biological rhythms. Natural circadian entrainment has been a fundamental feature of the evolution of life and has guided the rhythmic behaviour and physiology of higher organisms. In recent centuries, natural entrainment in humans has been replaced by artificial entrainment, with ample evidence for maladaptive physiological and psychological responses. By assessing which behavioural, molecular and neurobiological features are disturbed by manipulating these external signals, our results will be of considerable interest to the scientific and lay community.