Biological Clocks

INsecTIME laboratories and SMEs have one unifying goal: improving our understanding of biological rhythms, both circadian and seasonal clocks.

Circadian clocks

Circadian clocks are molecular mechanisms that regulate biological processes which display an endogenous oscillation of about 24 hours. These rhythms have been widely observed not only in humans, but also in plants, animals, fungi and even in tiny organisms such as bacteria. They allow organisms to predict, instead of merely react to, the daily environmental fluctuations due to the Earth’s rotation around its axis.The term circadian comes from the Latin circa, meaning “approximately”, and diem or dies, meaning “day”. Circadian rhythms are  self-sustained, that is why astronauts or people isolated from the environment still show a 24 hour sleep-wake pattern. Nevertheless biological clocks can be synchronised to the local environment by external cues such as daylight. It would not be very convenient nor advantageous to feel sleepy and tired during the day time!
The genetic dissection of biological rhythms started in the early 70s, when the first  clock-mutants and clock-genes were isolated and characterised. Interestingly, chronobiology was the first research field to assign a genetic component to a behaviour. Even nowadays, more than 40 years later, we struggle with the idea that a mutation in a single gene can influence not only the way we look like, but also our behaviour. In particular, specific mutation in clock genes can make us more morning (lark) or evening-types (owl). In humans, the circadian clock regulate many aspects of our daily life: from sleep-wake patterns  to  hormonal levels, mood, body temperature and vigilance.

SnoozingWhat is the interest in biological clocks due to? Technological advances have permitted society to escape the temporal constraints usually imposed by the natural environment, thus allowing altered and irregular behavioural patterns, meal schedules and lightning regimes. These activities provide conflicting signals to the circadian clock, perturbing its synchrony and provoking serious physiological consequences. Even social commitments and hectic work schedules challenge our internal clock, causing a syndrome which is generally referred to as “social jetlag“.  Recently, a wide variety of diseases and health problems have been shown to be mediated or aggravated by chronic disturbance of the circadian clock. Shift-work, for example, provokes a continuous resetting of the circadian clock operated by the external environment, which causes sleep, gastrointestinal and cardiac problems, hypertension, obesity and it has even been shown to correlate with cancer. Moreover, the efficiency of certain drugs is dependent on the time of delivery. It is thus possible to increase the therapeutic potential and minimize toxic effects by optimizing the timing schedule of drug administration.
Finally, malfunctions in clock genes are associated with several disorders such as chronic sleep disturbances, manic-depression or familial advanced sleep phase syndrome (FASPS). In particular individuals affected by FASPS show a 4-hours advance of the sleep, temperature, and melatonin (the “sleep hormone”) rhythms which is caused by a single mutation in a clock gene called period. This was the first clock gene to be identified in the model organism the fruitfly, and it is also found in humans. Indeed, the molecular components of the circadian clock are highly conserved between mammals and insects. This means that studying insect model organisms can give us significant  insight of how the human clock works and on how to enhance the ‘chronobiology’ of human  health.

Seasonal clock

Seasonal clocksUnlike circadian clocks, seasonal clocks regulate those physiological and behavioural processes which repeat themselves with a period of 12 months. In fact all living organisms are not only exposed to changes which occur every 24 hours, but also experience temperature and day length changes throughout the year. These seasonal changes are caused by the Earth’s axial tilt and its rotation around the Sun. As we all experience regularly, our appetite, mood, weight, sleep length and fertility change throughout the year. In some cases, especially in extreme environmental conditions, the extent of these cycles can become pathological.
The correlation between seasons and depression, suicide and suicide attempts has been known for years but the syndrome of Seasonal Affective Disorder (SAD) was first described in 1984. It is characterised by symptoms such as depression, irritability, increased sleep length and weight gain, which recur annually in wintertime. SAD is triggered by the lack of light exposure and it can be alleviated by light treatment. Studying the molecular mechanism of the seasonal clock in Model organisms such as insects, and the way it adapts to the environment, can provide us with better understanding of how the human seasonal clock works, and can contribute in developing new techniques to deal with season-related health issues.

Moreover, in insects, clock gene variants affect seasonal diapause (the insect equivalent of mammalian hibernation). When winter approaches, the daily photoperiod gets progressively shorter as the temperature falls. Insects use these changing environmental stimuli to i) initiate energy storing, essential to overwinter successfully and ii) stop reproduction. The study of timing genes has broad implications for intervening in the life cycles of insects of agricultural and commercial importance.

Here you can find the list and details of the insects used within the INsecTIME consortium.