A fruit fly clumsily approaches my wineglass, and I know that, inevitably, it will encircle my head a number of times while I throw misjudged swipes, interrupt the conversation and make me appear tipsier than I am. Because of this, I generally regard them as an annoyance. But then I spent a summer actually getting to know them, and started thinking of fruit flies – one species in particular; Drosophila melanogaster – as something of tiny heroes.
Surprisingly, this insect is one of the most intensively studied creatures ever to have lived on earth, likely surpassing even ourselves. Drosophila are an ‘invertebrate model’; useful analogues to humans for studying a massive number of biological processes.
But why the fruit fly? Surely it is one of the last animals you would choose to compare to humans? In fact, there are equivalent genes for 77% of known human diseases in Drosophila. Fruit flies share the fundamental cell chemistry of us and other animals, making them ideal for studying the way our cells work. They are cheap to look after and reproduce quickly. The entire genome is sequenced and available for scientists to study, and having only four pairs of chromosomes (compared to our 23 pairs) are easy to manipulate in studies.
Neuroscience is one example of a field which has benefitted fantastically from the use of Drosophila in research. First introduced into the field over 100 years ago, the humble fruit fly helped to decipher the complicated development of the nervous system. The genes involved in this development also turned out to be involved in leukaemia and some other cancers. Further research using Drosophila enlightened scientists on the molecular workings of behaviour, memory and circadian rhythm – which also revealed genes responsible for genetic sleep disorders.
Devastating degenerative diseases of the brain are currently being studied ferociously. They are expected to affect 35% of the European population, and Drosophila has once again come to the aid, being used in Alzheimer’s, Parkinson’s, Huntington’s, and prion disease studies. Scientists use them to study disease genetics, pathogenesis (how the disease progresses), and pathophysiology (how the disease alters normal body function). Exciting also, is the testing of new drugs which could prove useful in treating people with these debilitating diseases.
The prion diseases (also called transmissible spongiform encephalopathies, because of the spongy appearance they cause in affected brains) are a group of invariably fatal neurodegenerative diseases, including ‘mad cow disease’, Scrapie and variant Creutzfeldt-Jakob Disease (vCJD). Recently a research group developed the first Drosophila model of prion disease, using Scrapie (the sheep version of the disease) as a prototype for studying prion diseases.
Drosophila don’t actually have the prion protein, a normal cellular protein of mammals which misfolds and accumulates in the brain of animals with prion disease, so first the gene had to be introduced into the flies. This was achieved and various experiments were undertaken to ensure the presence of this normal protein would not cause disease in the flies. Once satisfied, the flies could be fed the misfolded prion protein, believed to be the infectious agent in the prion diseases, to see if the disease could be mimicked in the flies.
Amazingly, the flies did show signs of neurological disease after being exposed to diseased sheep brain! The prion diseases cause ataxia in mammals – the inability to move in a coordinated fashion. The flies were having difficulty moving, and died younger, as the misfolded prion protein in their food caused the prion protein their cells to misfold too. But that was not all. The misfolded prion protein within these flies could be transmitted from one fly to another – similar to the way natural infection occurs in mammals.
Suddenly, the experiments could occur in a matter of weeks. The acceleration in data collection should mean this mysterious disease, thought to be caused by proteins rather than a virus, bacterium, fungus or parasite, could see the mechanism of protein misfolding revealed in the near future.
Luckily the incidence of mad cow disease has dropped significantly since the changes in the food chain introduced in the 1990’s. However, the way in which prion protein misfolds and causes further normal prion protein to misfold, is very similar to a number of other diseases. Notably, Alzheimer’s, Parkinson’s and Huntigton’s diseases. Elucidating the mechanism of protein misfolding could see drugs developed to halt this misfolding, thereby stopping the progression of these horrendous diseases.
Next time the fruit fly is encircling me and my wine, I think I’ll raise a glass to this heroic little critter and to the scientists devoted to revolutionising the way we study disease and reducing the number of animals in research.