It's small and ugly but it might be key to a major advance in medicine

THEY live for less than 30 days, measure only three millimetres and survive mostly on a diet of spoiled fruit.

But now a breakthrough by scientists in Scotland is set to ensure that the simple fruit fly plays a key role in the understanding of human diseases, from cancer to infertility to Alzheimer's.

The Scotsman has learned that groundbreaking images of the internal workings of fruit flies have been developed by Medical Research Council scientists in Edinburgh. This will

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allow researchers to track how serious illnesses interact with the genes of the fly.

Until now, experts have had to dissect the fruit fly - Drosophila melanogaster - to understand the internal changes.

The key to such research lies in the fact that fruit flies, while looking very different to humans, are surprisingly similar - at least in the genetic sense.

News of the research comes as another study in the United States used the flies to help identify a "skinny" gene which determines whether humans will get fat or not.

Taking apart the tiny brain - measuring less than a millimetre - is a laborious process which can take hours and be wasted if the tissue is damaged in the delicate process.

The new technique - called optical projection tomography (OPT) - means this is no longer necessary, speeding up vital research into debilitating diseases such as Parkinson's and Alzheimer's.

Dr Mary O'Connell, who led the research at the MRC's Human Genetics Unit, said that the gradual loss of brain-cell function was not just a human phenomenon. "Insects are affected by it, too. In the autumn, bees and wasps often develop erratic behaviour before they die," she said.

Dr O'Connell said that because the fruit fly and humans shared many genes with similar functions, the creature was widely used by genetic researchers to study how genes influence human disease.

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"It is already known that defects in the equivalent fly genes involved in human brain diseases cause brain cells in fruit flies to lose function as they age," she said.

The new techniques to image the flies' brains will help scientists look at any changes that occur when genes are manipulated.

Dr O'Connell said eventually they hoped to test drug compounds on the flies to see how the disease was affected.

This would then pave the way for other researchers to look for similar chemicals which could be used in drugs for humans.

Leeanne McGurk, a PhD student who had previously spent hours dissecting the flies and who captured many of the new images, explained why the new technique was so important. "The dark colour of the fly exoskeleton prevents us from seeing inside it using a standard light microscope.

"In the past, this has meant scientists have had to tease apart fruit-fly tissues by hand.

Now, we have got over the problem by bleaching the fly exoskeleton.

"When the fruit fly becomes colourless it is possible to use imaging techniques not only to view its internal organs but to generate 2-D and 3-D images of the entire fly."

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The MRC unit, sited at Edinburgh's Western General Hospital, is one of many across the UK and thousands around the world using fruit flies to extend knowledge of the key role genes play in the development of illness.

The building's light and modern reception soon gives way to a den of offices and laboratories.

The labs are a scene of organised chaos. Workers in white coats sit at benches crowded with test tubes, petri dishes and other scientific paraphernalia.

Among the clutter sit plastic tubs containing the fruit flies which have held the key to so many advances in medical science.

Sitting in his office at the unit, Dr Liam Keegan says the flies are only the first step in a long process to treatments being developed for humans.

But it is an important step, and one which would take much longer if researchers were starting their work in more complex animals such as mice, he said.

"These flies are extremely important because they are very similar to us in many ways which are not immediately obvious.

"Fruit flies and humans had a common ancestor somewhere in the very distant past, possibly 600 million to a billion years ago.

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"Most of the genes that affect function would be common in flies and humans, while there are others which dictate how we develop differently.

"But with the internal wiring, a lot of it is common."

Because labs do not need special licences to conduct research using fruit flies, as they would with mice or other mammals, they have become a favourite among scientists across the globe.

For about 100 years, fruit flies have been helping extend understanding of human disease.

The fruit fly has only four pairs of chromosomes - compared to 23 pairs in humans - and a relatively small number of genes - 13,600.

This makes fruit flies easy to work with, and yet the proteins produced by those fly genes - proteins that control almost every process of life - are similar in flies and humans.

During the past decade, researchers have started to find them useful in looking at diseases affecting the brain.

In the MRC unit, millions of fruit flies are used each year. In one room, temperature-controlled cabinets house many of the flies.

In an adjoining lab, flies sit in trays on desks awaiting inspection under the microscope. Dr Keegan explained that the flies have been bred to act as a model of human diseases, with genes added or manipulated to make them as close to human illness as possible.

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He said his team focused on basic discoveries using fruit flies - it was then up to other researchers and drug companies to take up these findings and translate them into further tests on animals and eventually into treatments. But the research is not only limited to diseases affecting the brain.

The team also hope to use the new imaging techniques to study the fly's whole anatomy.

The shape and size of organs can be affected by diseases such as diabetes, so imaging could lead to clues into the development of diseases like that as well.

Dr O'Connell said fruit flies were a "key signpost" in the search for new treatments. "They help tell us what genes are having an impact and which genes are not having an impact in diseases.

"They are helping us with a whole range of diseases and will continue to be an important part of the work that is going on around the world," she said.

Why a modest creature is so popular with researchers

COMMONLY known as the fruit fly, Drosophila melanogaster is one of the most used organisms in biological research around the globe.

• In warm climates, the fly can develop from egg to adult in just seven days.

• In a temperature of 29C, fruit flies can live for about 30 days. In scientific laboratories, researchers can manipulate their environment to slow down their development so they survive for up to 60 days.

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• Female fruit flies lay about 400 eggs when fertile. These develop best in environments like rotting fruit and decaying mushrooms.

• The creatures are most at home in warm climates and are not present in large numbers in the wild in the UK. They are usually found in countries south of the equator.

• Fruit flies are popular for use in research because they are small and easy to grow in the lab, with females laying hundreds of eggs a day.

• Researchers do not need a licence to use flies as for other animals used in experiments.

• They are particularly used in genetic research because they share many of the same key genes with humans.

• In 2000, scientists identified the whole of the fruit fly genome - the complete set of genetic information of an organism.

• Scientists believe that about 75 per cent of human disease genes have a recognisable match in the genetic code of the fruit fly.


LAST year scientists took a batch of fruit flies on a 13-day journey into space to see what impact this would have on their immune systems.

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The NASA researchers wanted to examine the stress their tiny bodies went through while in space.

When they returned from their trip, the scientists took blood samples in the hope of finding clues to how extended trips into space might affect humans.

Researcher Laura Higgins said the flies were normal on their return from space.

"They didn't act weird or anything. They didn't come back with two heads," she said.


A STUDY earlier this year found the fruit fly may hold the key to new treatments for human liver diseases and diabetes.

Scientists at the National Institute for Medical Research identified the cells responsible for breaking down fat in the fruit fly. They said that the process was similar to that used by humans, meaning new drugs could be developed by experimenting initially on the fruit flies.

Many of the important steps in metabolising fat molecules and converting them into energy take place within the liver. But when this goes wrong, serious illnesses can develop.


SCIENTISTS have used fruit flies in research looking for potential cures for infertility.

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A team from the University of California, San Francisco, succeeded in curing infertile flies by switching on sperm production by injecting a key gene known as Boule.

It is hoped that the research could lead to developments in humans, where infertility is an increasing problem.

The researchers looked at flies that were unable to produce sperm because of the loss of the gene which controls the division of sperm and egg cells.

The same gene is found in humans, meaning it could be a target for fertility treatments.


SOME researchers have suggested fruit flies could hold the key to a possible treatment for alcoholics.

While fruit flies survive by feeding on fermented fruits, they do not get addicted to alcohol.

Researchers in the United States said that the same genes which stopped flies getting addicted were probably present in humans.

Triggering changes in these genes could stop alcoholics from drinking, they said.

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Genes could also potentially be manipulated to stop humans from becoming tolerant to alcohol, the researchers added.

'Skinny' gene research offers hope of drugs to tackle obesity

A SINGLE, "skinny" gene might control whether or not someone will pile on the pounds, researchers studying fruit flies said yesterday.

A study in the United States found that the adipose gene was likely to be a "high-level master switch" that tells the body whether to accumulate or burn fat.

Writing in the journal Cell Metabolism, the researchers said their findings might lead to new treatments to fight obesity and diabetes.

The research might explain why supermodels such as Britain's Kate Moss maintain their perfect figures while other people struggle.

The adipose gene was first discovered in fruit flies more than 50 years ago. But how it works and whether it interacts with other genes has been a mystery until now.

The team from the University of Texas used fruit flies, worms and mice to examine how the adipose gene works.

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The researchers, led by Dr Jonathan Graff, were able to manipulate the gene - which is also present in humans - to turn it on and off at different stages of the animals' lives and in various parts of their bodies.

They found that making the gene more active improved the animal's health in a number of ways.

Mice with increased adipose activity ate as much as normal mice. But, despite this, they were leaner, had greater resistance to diabetes and had better blood sugar control.

Those mice where the activity of the adipose gene was decreased were fatter, less healthy and had diabetes.

Dr Graff said: "From worms to mammals, this gene controls fat formation.

"It could explain why so many people struggle to lose weight and suggests an entirely new direction for developing medical treatments that address the current epidemic of diabetes and obesity.

"People who want to fit into their jeans might someday be able to overcome their genes."

How active the gene was affected how fat the animals become - from slim to medium to obese.

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"This is good news for potential obesity treatments, because it's like a volume control instead of a light switch," Dr Graff said.

"It can be turned up or down, not just on or off. Eventually, of course, the idea is to develop drugs to target this system. But that's in the years to come."

The researchers said that the genetic mechanism found in the adipose gene made sense in terms of survival.

If a population had many versions of the gene scattered across many individuals, at least some would survive different conditions.

This could mean that a fat fruit fly is able to survive a famine, but a slimmer fly is better at evading its predators.

But with today's sedentary lifestyles among humans, the purpose of the gene might be backfiring.

Figures show that obesity is increasing rapidly in the western world.

For example, around 26 per cent of women in Scotland are obese and overall 65 per cent of Scottish men and 60 per cent of women are overweight or obese.

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Children are sadly following in their parents' footsteps. Figures show that 21.8 per cent of Scottish children in their first year at primary school are now overweight or obese, compared with a figure of 19.7 per cent in 2000-1.

Dr Graff said the next step in their research was to get a better understanding of the exact mechanisms by which the gene had control.

While its function was not known at the time, the adipose gene was first discovered 50 years ago when Winifred Doane - now a professor at Arizona State University - noticed that some fruit flies contained more fat than others.

Many researchers have been trying to harness the genetic influences which cause obesity in the hope of finding new treatments.