Learning from fruit flies
Humans have fruit flies to thank for breakthroughs in life-saving drugs and treatments for mental illness, writes David Tan
When you look at the humble fruit fly, it is difficult to imagine how you could be in any way similar to it. With its large, red compound eyes, silvery wings and yellow-and-black-striped body, the fruit fly appears to be a world apart from human beings.
However, appearances can be deceiving and scientists are discovering just how alike these little critters are to us.
The fruit fly, or Drosophila melanogaster in scientific speak, is widely used in research because it shares about 60 per cent of human genes. About 75 per cent of disease-related genes in humans have a counterpart in these flies.
For more than 100 years, fruit flies have been used for scientific research, allowing breakthroughs in genetics, body structure and function. The first gene for jet lag and the first learning gene were identified in flies.
In April, researchers from Britain published the first ever basic training package on the best ways to use the fruit fly for research. It is hoped the guide will encourage more researchers working on a range of conditions, from cancer to Alzheimer's disease, to use the humble fly.
"Flies need very little space so are ideal for breeding. They develop in just two weeks and it is a simple process to follow a genetic mutation through the generations by analysing the patterns on their bristles, wings or eyes which provide easy visible markers," says Dr Andreas Prokop of the University of Manchester, who co-developed the training package.
Our brains control behaviour in a "strikingly similar" way, according to a recent study. Comparing the central brain regions in fruit flies (called the central complex) and humans (the basal ganglia), scientists found that these structures were organised similarly.
Dr Frank Hirth, a senior lecturer at the King's College London Institute of Psychiatry who conducted the research, says the way flies and humans respond to basic survival situations are controlled by common systems in the brain.
"Flies, crabs, mice and humans all experience hunger, need sleep and have a preference for a comfortable temperature, so we speculated there must be a similar mechanism regulating these behaviours," Hirth says.
"We were amazed to find just how deep the similarities go, despite the differences in size and appearance of these species and their brains."
Glial cells make up about half of the human brain, providing support for neurons, forming connections between brain cells and controlling the flow of blood. They are also important in diseases; for example, they are the main component of glioblastomas, a type of brain tumour.
But scientists still don't fully understand how they function, says Dr Lynette Foo, a postdoctoral fellow with the Institute of Molecular and Cell Biology in Singapore. Foo is using fruit flies to find the answers, zooming in on a particular group of molecules known as micro-RNAs which control various aspects of glial cells.
"The simplicity of the fruit fly nervous system coupled with the genetic tools that enable us to genetically manipulate cells in vivo [in living flies] make fruit flies a very useful and powerful system," says Foo. "We can attempt to understand how specific genes work in a simplified context and apply the knowledge gained to the more complex mammalian system."
Fruit flies are also helping scientists develop new treatments for neurological disorders, by revealing disease pathways of conditions ranging from sleep disturbances and attention deficits, to autism and schizophrenia.
Hirth describes the recent discovery of a signalling pathway in Parkinson's disease, which was first found in flies and later validated in human patients. The malfunctioning pathway causes mitochondria, the energy engines of cells, to fail. Cells become depleted of energy and degenerate, leading to movement problems and brain defects.
"Diseased fruit flies show several characteristic features of human neurological disorders, including problems with movement, sleep disturbances and memory deficits, as well as age-related degeneration of nerve cells. Therefore, identifying disease pathways in fruit flies is a reasonable means to begin to find treatments," says Hirth.
In one such study, researchers from the Tel Aviv University in Israel, led by Dr Daniel Segal, tested the common sweetener, mannitol, on fruit flies with a form of Parkinson's. Mannitol can enable drugs to enter the brain from blood, breaching a barrier that normally exists between the blood and brain to prevent infection.
Of key interest is the sweetener's ability to prevent the build-up of a sticky protein that gums up a part of the brain among Parkinson's patients. Fruit flies with a form of Parkinson's caused by this gummy protein are unable to climb the walls of a test tube, indicative of "severe motor dysfunction". When such flies were fed mannitol, the scientists found that the gummy protein in their brains decreased by 70 per cent and they could eventually climb up the test tube walls.
To test treatments, diseased flies are given drugs to find those that can stop the disease, or at least slow its progression. Successful findings in flies must always be retested in human cells and in larger animal models such as mice. Because of the differences in size between humans, mice and flies, drugs are metabolised at different rates. The few candidates that pass many rounds of rigorous testing are then allowed to enter clinical trials.
Hirth recounts a successful case where vitamins were used to stop the degeneration of nerve cells in fly models of Parkinson's. "After several successful tests in other models, these findings are currently being tested in clinical trials [in human patients]."
The similarities between humans and fruit flies aren't just internal. Externally, while human skin and a fruit fly's hard casing may appear completely different, both serve the same purpose of protecting against injury, infection and dehydration. Because of this, the outermost cells of both humans and flies respond to some of the same signals.
In the laboratory of Professor William McGinnis of the University of California San Diego, researchers established that the immune system kicks in as soon as the fly's casing is breached. This first response prepares the fly to fight against bacterial or fungal infection. The next wave of response involves proteins that repair the wound, followed by activation of processes that colour the healed outer casing.
McGinnis' team found eight molecules that previously had not been known to participate in wound healing. These components are usually not present or present at low levels, and are only called into action once injury occurs. Scientists are now exploring if the same molecules in humans play comparable roles.
"One amazing application of our studies may be to build a better bandage containing compounds to promote wound healing," says Dr Michelle Juarez, a member of McGinnis' team.