When I tell people about the research we’re doing in my lab, everyone’s first question is always how do you give flies Alzheimer’s disease? Followed by how can you find out anything useful from a fly? They’re both valid questions which I didn’t understand for a long time, so I’ll try and briefly explain the answers here.
The answer to the first question – how do you give flies Alzheimer’s disease – is that actually, you can’t. There is no one cause of Alzheimer’s disease. It appears to be caused by multiple cell mishaps which I’ll talk about in another post. This complexity and the fact it isn’t completely understood means you can’t replicate the full disease in any model. But you can replicate certain features. By over-expressing or under-expressing certain genes in the fly, you can induce changes in the ‘phenotype’ i.e.- a behavioural or physiological change (or both). Not only that, it is also possible to express human versions of genes (in true ‘Cramps’ style) in the fly to give a more accurate depiction of what happens in the human disease.
You don’t often associate flies as having behavioural traits like learning and memory, but actually they do. Flies are capable of long term and short term memory which has found to be altered with age, just like in humans. Now obviously, humans have a much more sophisticated and complex neuroanatomy to allow more complex memories, but the underlying basic circuitry in the brain is very similar between us and the flies. This means we can train them to remember and we can track differences in the animals with Alzheimer’s like symptoms. We can use cheap and simple experiments to measure these behaviours. For example, my work uses an experiment where we teach the flies to evade their normal response to go towards light. We can train them to associate light with a chemical called quinine which they don’t like the taste of. Later on, we can then assess whether they have remembered to associate light with something they would normally avoid.
There are many other behavioural experiments to examine changes in flies with different genotypes, but there is also biochemical data that can be found. For example, you can look at fly brains under the microscope and image certain neuronal tracts using fluorescent staining. This is a pretty cool technique and lets you see changes that occur to neurons in Alzheimer’s brains. Not only this, but you can also use live larvae to image axonal transport (transport of molecules up and down neurones). Because fly larvae have clear cuticles, you can see right into their bodies and when a fluorescent dye is added, you can actually video the neurones doing their thing!
Now you may still be wondering why you would choose a fly to do these assays, but there is a very straight forward answer – flies are cheap and much easier to look after. Plus you can get very convincing results with a large number of flies very quickly. A fly also has a maximum lifespan of about 3 months meaning that experiments involved in ageing (a very important factor in Alzheimer’s research) can be done easily. A mouse, for example, has a lifespan of a couple of years so ageing experiments are much harder and more expensive.
So yeah, flies are pretty good for lots of reasons. Just not when they eat your fruit.