Some Like It Hot, Except for Epileptic Fruit Flies
Last weekend, I was at Haymarket doing some shopping. If you’ve never been to Haymarket, it is an open farmers market in Boston where vendors sell wholesale produce. The last time I was there, I bought a pineapple, 10 limes, 5 lemons, a box of strawberries, a box of raspberries, 6 plumbs, 3 pounds of tomatoes, 3 sweet potatoes and a pound of green beans for $12.
Although its a steal, you have to be mindful of the quality. Many times I will pass a vendor who has fruit a day or two past it’s prime swarmed by flies. I noticed this again yesterday, and I started to remember my undergraduate freshman biology course.
Fruit flies have been a staple of genetic research since the early 1900s. As technology progressed, research moved toward using mammalian models, since they were more closely related to human beings. I seldom hear of fruit flies being used in research now, especially in studies concerning human disease. Curious, I began searching the internet when I came across an article recently published in the Journal of Neuroscience that used fruit flies to study epilepsy.
Researchers from Brown University and UC Irvine have devised an experiment using a knock-in fly model to study the underlying mechanisms that cause GEFS, otherwise known as Genetic Epilepsy with Febrile Seizures. The seizures related to GEFS are temperature sensitive and are triggered by fluctuations.
Mutations in the human SCN1A sodium channel gene are linked to GEFS. Using homologous recombination, researchers integrated mutated versions of SCN1A into the drosophila para gene, which is very similar to SCN1A. Homologous recombination requires the use of a transposable element (which moves chunks of DNA) to transfer SCN1A, and DNA repair mechanisms to insert it. Robert Reenan, co-author of the paper and biology professor at Brown University, and his team were able to trick the cell into placing the mutant SCN1A gene into a location that corresponds to it’s location on the human X chromosome using this technique.
“This is the first time anyone has introduced a human disease-causing mutation overtly into the same gene that flies possess,” said Reenan in a press release.
Once the mutant flies were developed, researchers exposed them to temperatures reaching 104 degrees Fahrenheit. After 20 seconds, they began exhibiting symptoms of seizures: leg twitching, abdominal curling, wing flapping, as well as being unable to stand. It took approximately an hour for the flies to recover. When the researchers exposed control flies with no mutation to the same environment, they saw no seizure activity.
Credit: Reenan Lab, Brown University
Reenan’s collaborators at UC Irvine, lead author Lei Sun and his team, studied the internal workings of the flies’ brains. What was happening in the brain to cause the seizures? They found the SCN1A mutation cause sodium transport channels in the cell membranes of neurons to malfunction. Usually, neurons regulate electrochemical signals that affect brain activity. Sodium channels play an important role in this process. In the case of the seizing fruit flies, the channels pass too much current. This effect was exacerbated by the high temperatures the flies were exposed to at Brown University, causing seizures.
Potential directions of future research includes searching for genetic mutations that would counteract or silence the SCN1A mutation, eliminating seizures. That technique is difficult to do in mammalian models due to the complexity of their genomes. Fruit flies have only 4 pairs of chromosomes, compared to the 20 pair mice have and the 23 pair humans have. As well, fruit flies have short generation times and are easy to care for. Will fruit flies emerge as a new model for human disease study? Only time will tell.
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