Here's what the Nobel Prize for Medicine winners did to get their award

A trio of Americans are this year's laureates.

An American trio who have been working on unravelling the inner workings of our biological clocks since the 1980s have been awarded the Nobel Prize for Medicine.

Here’s what Jeffrey C Hall, Michael Rosbash and Michael W Young did.

What is a biological clock?

Humans have long been aware that living organisms have an internal clock that keeps them in sync with the natural rhythms of the day – helping us adapt to day and night.

In the 18th century, astronomer Jean Jacques d’Ortous de Mairan discovered that mimosa plants, whose leaves open towards the sun during the day and close at dusk, continued to follow their regular daily oscillation even when placed in a dark room for the entire day. This gave the impression that plants have their own biological clock.

Other researchers discovered the same thing with animals and humans – that some mysterious inner workings helped prepare us physiologically for the fluctuations of the day. This became known as the circadian rhythm.

Identifying the cause

The work that Hall, Rosbash and Young won an award for was started in the 1970s by Seymour Benzer and his student Ronald Konopka, who asked whether it would be possible to identify genes that control the circadian rhythm in fruit flies.

They showed that mutations in an unknown gene, which they named “period”, disrupted the internal clock of flies – but little was known about how this actually worked in practise.

Hall and Rosbash, who were working together on fruit flies at Brandeis University in Boston in 1984, managed to isolate the period gene and discovered that PER, the protein encoded by period, accumulated during the night and was degraded during the day.

This showed that PER protein levels oscillate over a 24-hour cycle, in sync with the circadian rhythm.

Figuring out how it works

After doing all the work to identify the genes that control our circadian rhythm, the laureates still had no idea how our biological clocks actually worked.

Hall and Rosbash hypothesised that the PER protein blocked the activity of the period gene, which might help explain how the circadian oscillations could be generated and sustained. But, there wasn’t enough evidence to back this up.

To block the period gene, PER – which is produced in the cytoplasm – would have to reach the cell nucleus, where the genetic material is located. Hall and Rosbash had shown that PER builds up in the nucleus overnight, but had no idea how it got there.

In 1994, Young discovered the first of two genes that would help prove the other two scientists’ hypothesis, and provide us with the knowledge about how our biological clocks come to be.

Timeless, the first gene Young discovered, encoded the TIM protein that was required for a normal circadian rhythm.

Young showed that when TIM bound to PER the two proteins were able to enter the cell nucleus, where they blocked period gene activity to close the inhibitory feedback loop – thus allowing the PER protein to prevent its own synthesis and regulate its own level in a continuous, cyclic rhythm.

And when Young later discovered the gene doubletime, which encoded the DBT protein that delayed the accumulation of the PER protein, it showed how oscillation frequency is controlled more closely match a 24-hour cycle.

The mechanics behind our biological clocks had finally been understood.

The laureates went on to identify additional proteins required for the activation of the period gene, as well as for the mechanism that allows light to synchronise the clock.

Why it’s important

Our biological clocks help regulate a large proportion of our genes, as well as critical functions like behaviour, hormone levels, sleep, body temperature and metabolism.

The inner clock adapts our physiology to the different phases of the day, and a mismatch between our external environment and our body clock can affect our wellbeing – think jet lag.

A big difference between lifestyle and inner clock has also been linked to an increased risk of various diseases.

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