Behind the scenes in the Fly Room

Lab manager Anna Cyrklaff takes a tray of fly specimens to be transferred into new vials
Lab manager Anna Cyrklaff takes a tray of fly specimens to be transferred into new vials. PHOTO: Marietta Schupp/EMBL

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Curious about what goes on in EMBL’s Fly Room? Prepare to be a fly on the wall

One of the most intriguingly named rooms at EMBL in Heidelberg is the Fly Room. Inside, all of one wall and most of another are filled with shelf upon shelf of vials, each containing Drosophila melanogaster – the common fruit fly. Alongside the shelves are a series of workstations equipped with microscopes and paintbrushes. Seated at one of these workstations, EMBL staff scientist Imre Gaspar takes a vial of flies and a handheld instrument that looks like a smaller version of the nozzle you use to fill your car with petrol. Instead of dispensing fuel, however, this nozzle emits carbon dioxide. Gaspar slides it past the cotton wool stopper on the vial and uses it to anaesthetise the flies inside, so he can study them.

Staff scientist Imre Gaspar examines fly specimens

Staff scientist Imre Gaspar examines fly specimens. PHOTO: Marietta Schupp/EMBL

“This used to be done with anaesthetics like ether,” says Gaspar. “I’ve used ether on flies in the past but after a while it can make you feel dizzy, so carbon dioxide is a better choice. It temporarily anaesthetises the flies, so they lay motionless under the microscope. You can then use a paintbrush to sort the flies according to whether they have the characteristics you want.”

Working with flies

If researchers want to understand what a particular gene does, they often need to study a fly strain that’s missing a copy of that gene, or has a mutation in it. Usually this won’t cause any visible change to the fly, so changes to the fly’s genome are made with an associated marker gene that does have a visible effect. There are various commonly used marker genes, including ones that produce white eyes (fruit flies normally have red eyes), notches in the ends of the wings, or wings that curl upwards, away from the body. The sorting process with a microscope and paintbrush can therefore be carried out by looking for these changes in the flies. The selected flies can then be studied, or crossed with other flies to create a new strain.

After the flies have been anaesthetised with carbon dioxide, a paintbrush is used to sort them under the microscope

After the flies have been anaesthetised with carbon dioxide, a paintbrush is used to sort them under the microscope. PHOTO: Marietta Schupp/EMBL

These fly strains are used by many research groups at EMBL, most often to understand aspects of fly embryo development, which is coordinated by a precise sequence of interactions between parts of the fly’s genome and its associated proteins. While flies might seem far removed from humans, the process of embryonic development is similar across the animal kingdom, and many other fundamental cellular processes are similar too. Research on flies can therefore provide important insights into the way human embryos develop, and the way our cells behave.

Because of this close link to development, the Fly Room is located in and run by the Developmental Biology unit at EMBL, but the flies that are bred here are used by fly researchers across EMBL.

Fundamentals of flykeeping

One important aspect of looking after flies is giving them the right food. In another part of the building, EMBL has a Fly Kitchen with dedicated staff responsible for fly food preparation. “Apart from some antibacterial compounds, most of the ingredients for the fly food are things you can buy in an ordinary grocery store,” explains Gaspar. “Things like yeast, malt extract, and apple juice. These are then mixed with agar and poured into vials, so the food turns into a gel as it cools. The vial is then ready to house and feed a new set of flies.”

Most ingredients for the fly food are things you can buy in an ordinary grocery store

Other important considerations are temperature and humidity. Ensuring that these are carefully controlled is one of the responsibilities of lab manager Anna Cyrklaff, who has run EMBL’s fly facility for almost twenty years. Aside from the main Fly Room, EMBL has several fly stock rooms that need to be kept at different temperatures – some at 18 °C, others at room temperature (around 21 °C), and others at 25 °C. “Stocks that are less important can be kept at 18 °C,” explains Cyrklaff. “They still survive but the time taken to produce each new generation of flies is longer and the stocks require less attention. On the other hand, fruit flies are most comfortable in the 25-degree room, which is close to their preferred temperature in the wild. There the generation time is around 10 days, so if you need to work as fast as possible, that’s where your stocks should go.”

The stock rooms need to have a humidity of around 50-60%. If it falls below that, flies lay fewer eggs and generally don’t live as long. “In the summertime the humidity often gets too high, so we might have to add more agar to the fly food to absorb water,” explains Cyrklaff. “And in the winter it can get too low. Usually we deal with this by adjusting the climate control system in the stock rooms, but in extreme cases you can add water to the trays where the vials are stored, to bring the humidity back up.”

Flipping flies

Another requirement for looking after flies is regularly ‘flipping’ them into new vials. This ensures that they have fresh food and that their waste products don’t build up inside the vial. Experienced practitioners like Cyrklaff and Gaspar are able to do this without allowing any flies to escape. They tap the vial on a table to make the flies fall down to the bottom, then quickly take out the stopper, tip the flies into a new vial, and put a stopper in it. This process needs to be repeated regularly – more often at higher temperatures where the flies are breeding more rapidly. At 18 °C it needs to be done every six weeks; at room temperature, every 20 days; and at 25 °C, around every 10 days.

Alongside the stocks of fruit flies that are kept in vials, Cyrklaff also regularly creates fruit fly population cages – larger containers holding many thousands of flies. These are used when EMBL researchers – whether in Heidelberg or at other sites – require large numbers of fly embryos to study.

You do feel a kind of pride when you see that a stock has produced many larvae

Has working so closely with flies made Cyrklaff and Gaspar look any differently at flies outside the lab? “Because of their various mutations, our laboratory stocks tend to be much less resilient than flies in the wild. Sometimes it’s very hard work to maintain them, so you do feel a kind of pride when you see that a stock has produced many larvae and they’re looking healthy,” explains Gaspar. “But that only applies in the lab. If I saw the same thing in my kitchen, I’d be disgusted!”

Cyrklaff agrees. “We definitely don’t enjoy breeding flies at home!”