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Dr Laura Tamberg, a researcher in the Tallinn University of Technology (TalTech), Department of Chemistry and Biotechnology, uses fruit flies in her research. In this interview, she talks about how she became interested in the flies and explains how these tiny insects are similar to humans.
Fruit flies tend to be considered annoying pests. How did you arrive at the idea of studying them?
When I came to TalTech to do my Master’s degree, I had no idea that I’d be working with flies. I just got in touch with Tõnis Timmusk, who’s a professor of neurobiology and the head of the neurobiology lab here. He said he’d take me on for my Master’s thesis, but told me that another Estonian researcher, Dr Mari Palgi, was coming over from Finland. She became my supervisor. She’d done her PhD in Finland using fruit flies, so she brought both the flies and her knowledge of them with her. That’s why a fly laboratory was opened here at TalTech, since there wasn’t one anywhere else in Estonia at the time.
So you’re working with Finnish fruit flies?
Actually no, they’re not brought across from Finland, since you can purchase them from specialist centres. For example, there are big fly stock centres in America where you can buy genetically different flies based on whatever you need. We’ve also created quite a lot of fly stocks of our own by modifying their DNA.
You use fruit flies in your research as well. Why and how have they become a popular model organism in research, and in what way are they similar to humans?
It’s actually a really exciting area. Fruit flies have been used in laboratories for more than a century. As early as 1901, a man named William Castle brought them into his lab at Harvard University. Toomas Hunt Morgan is also very famous for using fruit flies in 1910 to study genes. At the time, no one knew anything about genes or DNA, but Morgan used the flies to study how different traits are inherited.
He crossbred different flies and then observed how their traits were passed on. Since then, fruit flies have been used a lot in laboratory studies. And it’s not just here in TalTech – lots of labs around the world use them as model organisms in neurobiology, genetics, developmental biology and more.
Fruit flies are popular as a model organism because they can be used to study a wide range of human diseases. That’s made possible by the fact that around 75% of the genes associated with human diseases have a counterpart in the fruit fly. That means the gene carries the same function. Another advantage with fruit flies is that they’re easy to look after. They don’t need much space, and they have a short life cycle, just nine days at 25 degrees.
What does it mean when we say something is used as a model organism?
It means that studies of biology, life science, require a model; they can’t just be done in a test tube. And since we’re neurobiologists here in this lab, it’s obvious that we can’t use a human brain as a model for our research. Who’d want to offer up their own brain for it! That’s why different models are needed, and one of them is the fruit fly. We know that processes which happen inside the cell, such as signalling pathways, are very similar, or conserved. That’s because humans and fruit flies share a lot of homologous genes, which is to say genes that have similar functions.
I’m studying two intellectual disability syndromes in which a faulty gene has been found in humans. Patients with this faulty gene have severe intellectual disabilities and other problems. In both diseases, there’s a gene with a similar function in fruit flies as well. And if I introduce mutations to the genome of the fruit fly, or switch it off, or reduce its expression, then in addition to other traits, I can also observe that the flies are unable learn, for example.
We can measure learning and memory with flies, and the different molecular mechanisms that are disrupted in diseases can be studied. It’s good to start with a model as simple as a fly, because flies are easy to work with, easy to breed, and all the information we get from fruit flies can be translated to mammals like mice and rats, and perhaps one day even to humans.
You mentioned teaching the flies, but I assume you’re not teaching them that 1+1 = 2. So what exactly are you teaching them, and how do you even go about it?
Most people have probably heard of the “Pavlov’s dog” experiment. He taught the dog to associate food with the sound of a bell, and eventually, just ringing the bell was enough to make the dog salivate. What we’re doing is similar, and in fact is called Pavlovian conditioning. We use a specific odor that we expose the flies to, and then give them a mild electric shock.
We have this tube with the flies inside it, and when we release the odor, they get shocked. The flies should start associating that odor with something negative. Then we introduce a second odor, which they don’t associate with the shock. Finally, we give the flies a choice between the two odors, and if their memory’s intact, they avoid the odor associated with the shock.
You can also do the opposite, pair one odor with sugar and the other with nothing. When given a choice, the flies should gravitate towards the odor associated with the sugar. That’s positive learning through reward, but the other one is punishment-based or negative learning. We can then count the flies to see how many gravitated towards each odor, which can then be calculated so as to put a numerical value on their memory.
Do flies experience intellectual disabilities, or for example Alzheimer’s? If not, what do you need to do to them to induce intellectual disabilities or Alzheimer’s?
Alzheimer’s is being studied in the lab next door to ours, but I can explain briefly: because flies don’t have the gene associated with Alzheimer’s, researchers insert the faulty human gene into the fly. If the gene is expressed, they can measure memory or movement, like climbing. Normally, flies will always climb upwards along a tube, but when the Alzheimer’s gene is activated, they climb less or can’t climb at all and fail to learn.
Once we’ve created models for the intellectual disability or Alzheimer’s or whatever it is, we can administer drugs to them and see if the behavioural aspects improve. From there, perhaps one day the drugs will be able to be administered first to mice and rats, and eventually to humans.
Have there been any drugs that have cured sick flies or helped those with intellectual disabilities?
Yes! I’ve administered two to fruit fly larvae, which you can also do memory tests with. One of them is a naturally occurring substance, resveratrol, which is found in things like blueberries and red wine. It’s known to have memory-enhancing and anti-ageing properties. When we gave it to the larvae, their memories improved. The second drug was one used in cancer treatment that has a broad effect across the genome. That led to a small improvement in memory as well.
Earlier you mentioned fly centres. They sound fascinating, because I’m picturing that you put a banana or an apple on a table and the flies just come to them on their own.
We’ve bought or generated our own fly stocks here in the lab that live in special vials inside an incubator. The challenge is figuring out how to study them without them flying away. A carbon dioxide system was developed for that purpose, with a cushion under the microscope that releases the carbon dioxide from a cylinder when a pedal is pressed.
The flies live in vials with a cotton plug at the top. When we use a special pistol to release the carbon dioxide between the plug and the vial, they fall asleep. The percentage of carbon dioxide is low enough that it doesn’t do them any harm. Then we can take the flies out and use a brush to sort the females from the males under a microscope, since they need to be crossbred.
For that, we need virgin females who haven’t yet mated with males in the same vial. These are female flies that are up to eight hours old. When we want to crossbreed flies for an experiment, we take the virgin females and put them with the males we want them to mate with. To do that, we put them in a new vial, where they wake up a couple of minutes later.
All this can be done with flies that have been put to sleep using carbon dioxide. That way we can sort them, look for different traits and separate the females from the males.
Like playing with dolls?
It is! (Laughs) What’s also interesting is that the use of fruit flies has garnered scientists six Nobel Prizes. The most recent one was in 2017, for the discovery of circadian rhythm genes, or clock genes, in fruit flies. Similar systems are found in humans. Lots of important discoveries in developmental biology and neurobiology alike have been made using fruit flies.
So you might say that although they just seem annoying, these little insects are actually quite important and useful?
Very much so! They’re really interesting and important in biology.
This article was originally published on the webpage of TalTech (Tallinn University of Technology).
If this dive into the insect world has you buzzing with curiosity, don’t bug out just yet! Crawl over to our next article for more tiny but mighty discoveries! Read more about Green defense! New strategies to protect our crops and planet — insights from an interesting oilseed rape study.
