Abu Dhabi fruit fly study could shed light on humans’ body clock cycle
The insects are being studied to observe behavioural changes that may help to better understand how the body clock in humans works and when we are most active.
Some people are better at functioning in the morning, while others operate best in the evening.
Everyone is different in terms of how active they are over the course of a day, but almost all of us follow a 24-hour cycle of being awake and asleep.
Changes in behaviour over a day are also shown by creatures as simple as the fruit fly Drosophila, and a UAE researcher recently uncovered fascinating details about how these behaviours are controlled.
The work, led by New York University Abu Dhabi’s Prof Justin Blau, could help to shed light on the control of daily rhythms in people. It could even improve the understanding of spinocerebellar ataxia (SCA), a neurodegenerative disorder.
The research is using Drosophila as a model system in an attempt to gain a deeper understanding of how many different organisms function.
“It would not be so interesting if we had found something unique to the fly. We’re trying to find general principles of how the brain keeps time and how the brain works in general,” says Prof Blau.
Published in the journal Cell, the study involved an analysis of pacemaker neurons, which control the flies’ daily cycle of activity and sleep.
It was already known that the ends of these long nerve cells expand and retract with a 24-hour rhythm. Prof Blau and his co-researchers set out to find out the significance and the mechanism of these daily cycles.
Representing several years’ work by PhD student Afroditi Petsakou, the study, co-authored with Massachusetts Institute of Technology researcher Themistoklis Sapsis, involved measuring the activity of a large number of flies, some of whose pacemaker neurons were genetically altered.
Observing the flies was simpler than it might seem, as the researchers did not have to sit and watch the creatures for hours on end.
Instead, they made use of an ingenious automated system commonly used to study Drosophila.The flies were placed in a thin glass tube about 6.35 centimetres long with food at one end. An infra-red beam ran through the middle of the tube and a computer recorded each time a fly passed through the beam.
The computer counted the number of time segments in which the beam had been broken, and the number in which it was unbroken, to determine when flies were active and when they were asleep.
“We did this for hundreds of flies under summer and winter day lengths,” says Prof Blau, a Briton who studied as an undergraduate at the University of Cambridge before completing a PhD at the University of London.
These methods helped the scientists determine that a protein called Rho1 controls the daily changes in the pacemaker neurons, which in turn determine when the flies are active. They found that if pacemaker neurons are unable to expand, due to continuous Rho1 activity, flies behave normally when the days are long (such as in summer), but cannot adapt to the shorter days of winter. They are stuck in summer mode and wake up well before dawn.
By contrast, when Rho1 activity is suppressed, neurons can never retract fully and the flies show their winter pattern of behaviour, waking up later in the day regardless of the timing of dawn.
Over time, the results could be relevant to people because the Rho family of proteins are not just found in fruit flies – they are also present in mammals.
“There are also Rho proteins in humans. I would expect that at least one of them has a similar function in the suprachiasmatic nucleus,” says Prof Blau, referring to the region of the human brain that controls human pacemaker neurons and, in turn, our body clock.
He says that the research could lead to an improved understanding of SCA “in the next few years”, although therapy would be “a lot” further into the future.
Prof Blau has already been contacted by a researcher who found that a protein linked to Rho is important in timekeeping in mammals.
Beyond this, the recent study could be valuable for scientists looking to better understand, and to cure, SCA, even though this condition is not related to daily rhythms. People with SCA progressively lose their coordination, while their intellectual capabilities are left unimpaired.
“We found that Rho1 activity shows 24-hour rhythms in Drosophila pacemaker neurons and we identified the protein that controls these cycles. The human version of this Rho regulator has reduced expression [in people with SCA]. We don’t know when that starts but if it’s adult onset, then perhaps therapies could be developed that target this regulator,” says Prof Blau, who has helped to set up a fruit-fly laboratory in Abu Dhabi, in addition to his lab in New York.
One way of combating the effects of SCA would be to boost levels of the regulator that controls Rho activity in people with the condition. This could prevent their neurons from degrading as they age.
Prof Blau has worked with the fruit fly since 1996 and is unlikely to research these potential benefits to people himself. Instead, his aim is to gain a deeper understanding of how the activities of Rho are regulated in fruit flies and how Rho drives changes in the size and structure of these pacemaker neurons.
Those researchers who focus on the same systems in mammals are certainly taking on a major challenge. The array of neurons that governs daily rhythms in creatures like us is orders of magnitude more complex than in the fruit fly.
“There are only 150 pacemaker neurons in flies, while we have more like 50,000,” says Prof Blau. “It’s very hard to find out which are the dominant ones, let alone whether they are changing shape.”
Already, a lot of research is being done on Rho proteins’ effects on people, with medical applications ranging from understanding the genetics of certain kidney conditions to understanding the mechanisms behind some viral infections.
When researchers do uncover the secrets of how Rho activity in people is controlled, the potential benefits could be significant. And the modest fruit fly will be partly to thank for whatever breakthroughs are made.
Daniel Bardsley is a UK-based freelance journalist and former reporter at The National. He has science degrees from the University of Oxford and the University of East Anglia.
Published: October 3, 2015 04:00 AM