KAITLIN HARDY: Hi. I'm Kaitlin Hardy. I'll be a senior in CALS, studying neurobiology. We're here with the FACES Lab. FACES stands for Facts, Advocacy, and Control of Epileptic Seizures.
We started as a nonprofit, and now we have a research lab run entirely by undergraduate students. We have Amanda Estevez-- she'll be a senior; [? Raka ?] [? Banaje, ?] she'll be a junior; Sven Fors-- he's our entomology major, he'll be a sophomore; Kelsey Schmidt-- she'll be a junior, she's a chemical engineer; Sara Budic, who will also be a junior. And then we also have Maura Greenwood, who will be a senior and has been involved with FACES previously.
I myself have epilepsy, and about half of the people that are in this lab have a close friend or sibling who also has epilepsy. So this experiment really hits home for everyone who's involved. A lot of the drugs that we're working with are drugs that I've previously taken to try to control my seizures.
We work with different strains of Drosophila melanogaster, or fruit flies, that have been genetically engineered to be sensitive to seizures. Today we're working with bang-sensitive Drosophila. They have a mutation in their sodium channel that makes them susceptible to seizures.
Their seizures have a paralysis phase, just like humans, and then a violent seizure phase that lasts for 30 seconds up to two minutes. After that, they have a refractory period. So essentially, their seizure exactly mimics what a human seizure looks like.
We found a way to administer human antiepileptic drugs to the fruit flies in order to stop their seizures. So right now we're working with a sodium channel blocker. Then they have to be ground into a fine powder, because the flies obviously cannot ingest a pill that large. It actually takes a lot of work to grind them up. They're quite hard, and this is probably one of the more difficult tasks.
After the pills are ground into a fine powder, then they need to be moved over and dissolved in whatever medium we can dissolve them in. Not everything will dissolve readily in water, so sometimes we need to experiment with acetone or other liquids. Either way, you can't just put the powder on top of the agar, because the flies won't eat that.
We started with a very, very low dose. I think it was one ten-thousandth of what you would give humans. And then we started with a very high dose, which was almost 100% medicine compared to the food they're giving them. So the high dose killed the flies, the low dose didn't really have any effect, and then we just worked inward from there in increments of 10. It took about three weeks before we found a therapeutic dose.
It generally takes around 15 minutes for the agar to boil. And then once it cools, we have to work very quickly in a team. We almost form an assembly line to get the agar in and to get the medicine in and to have everything cooled sufficiently. After the food is set, we wait about 24 hours before we put flies on it to make sure everything's dry. We don't want any flies to die from getting stuck into the medication, because that would have a different effect on our studies.
--flies the drugs initially as adults. But then for the F2 generation, they'll be eating the drug as larva, so that's why we're starting to see birth defects as well. We're starting to see flies without wings, flies that are twice the normal size, flies who have different eye colors, because not only have their parents ingested the drug, but they're also ingesting it during the developmental phase. So there's some developmental repercussions of that. But now it's almost becoming an experiment on birth defects associated with antiepileptic drugs, which is really cool. So we're really excited about that.
After we found one dose that worked, we needed to move on to different fly mutations. There's different channels in the brain that can cause seizures, and therefore different antiepileptic drugs target these different channels. So next we'll be working with histone deacetylases to determine if we can stop those seizures as well.
After we finish looking at flies and how they handle their seizures on the medication, we're going to attempt to look at side effects of these medications. The side effects are something that I've struggled with for years. And now we're trying to finally prove using the flies that these medications do have a negative cognitive effect on whoever is taking them, humans are flies.
Flies can actually be classically conditioned. They're sensitive to both color and shock. So just like Pavlov's dogs, you can classically condition flies to go through some sort of obstacle course or decide where their food is or decide what kind of treatment to avoid. Fruit flies are actually a very good model for human epilepsy. We also know all about the Drosophila genome, so we can pinpoint exactly which genes are causing these mutations that make them sensitive to seizures.
Aside from knowing the entire genome, fruit flies have a very short life span and generations span. We know exactly when the larva will come, we know exactly when the flies will occlude, and we know exactly how long they're going to live. So we can closely monitor the entire life cycle and know what changes we're observing over those few days.
It's almost shocking how little research there is going on right now for epilepsy and seizure disorders, especially considering how common epilepsy is. It affects between 1% and 2% of the entire population, and it gets almost no research dollars. We're hoping that our research in flies is applicable to other research in humans so we can start to develop new drugs and look at new targets that don't have as many cognitive effects on whoever's taking them.
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A group of undergraduates led by Kaitlin Hardy is using "bang sensitive" mutant fruit flies to investigate the use of drugs designed to treat human epilepsy.
When these flies are given a mechanical shock they undergo seizures that are remarkably similar to human epileptic seizures. At least one of the drugs designed to treat human epilepsy protects the flies from this effect, suggesting that these mutant fruit flies may be a useful model for exploring other treatments.
Hardy is part of the FACES (Facts, Advocacy, and Control of Epileptic Seizures) research lab.