Looking into the fly’s brain
They take up little space and are easy to breed; because they are easy to look after, fruit flies or Drosophila melanogaster are used as laboratory animals in research institutes all over the world. However, that is not the only reason why they are one of the most important model organisms that are studied by geneticists. Another important reason is that their genetic make-up, which is readily comprehensible, has been completely decoded and is easy to manipulate. In addition, many of the findings that scientists arrive at by studying flies can be transferred to other organisms. By examining the fly’s brain, we can therefore gain a better understanding of the way human brains work.
“Many characteristics of the brain’s metabolism are phylogenetically preserved. That means that the processes which take place in a fly’s brain resemble those in a human brain. The similarities extend to the origination of diseases,” says Stefanie Schirmeier. The thirty-five-year old biochemist is a junior research group leader at Münster University’s Institute for Neuro- and Behavioral Biology. Aided by her research group, she studies how various sugars find their way into a fly’s brain and how they are metabolized by various types of cell within the brain. Among other things, Stefanie Schirmeier’s team has successfully shown that neurons – the brain’s nerve cells – are ‘fed’ by the glial cells that surround them. The glial cells, which also form the blood-brain barrier, extract sugar from the blood, and transform it into small molecules, which they pass on to the neurons. The blood-brain barrier is a natural barrier between the body and the brain. It prevents harmful substances and pathogens from getting into the brain. Highly specialized molecular transport mechanisms ensure that the brain receives all the necessary nutrients from the bloodstream and that waste from the brain’s metabolism is evacuated.
The brain cannot function normally unless sugars and other nutrients are properly transported. On average, a human brain makes up only two percent of the body’s weight, yet it consumes 20 percent of the oxygen in the blood. This is a clear indication that the brain requires a substantial amount of energy. A disruption of transport mechanisms or downstream energy provision to the neurons may be responsible for neurodegenerative disorders. “First of all we’d like to arrive at a proper understanding of how a brain functions under normal conditions,” says Stefanie Schirmeier, who in 2018 was awarded Münster University Society’s advancement prize for young researchers in recognition of her scientific work. “Unless we know exactly how the brain’s metabolism functions in a healthy individual, we won’t be able to understand what goes wrong when a disorder occurs.”
The “fly lab” used by the research group is a plain room of manageable proportions with workbenches on each side and shelves around the walls. On the shelves there are plastic boxes with small stoppered plastic tubes. Each tube contains some mushy food and hosts tiny fruit flies. When a layman looks at the swarms of insects in the tubes, they would find it hard to imagine that something which, though far from commonplace, has become part of a daily routine for the scientists who work here. The flies’ brains can be isolated and kept alive long enough for researchers to observe metabolic processes live under the microscope.
In order to make molecular processes visible, scientists reach into the molecular biologist’s bag of tricks and smuggle instructions for precisely fitting fluorescent sensors into the flies’ genetic make-up. When placed under the microscope and viewed under proper lighting conditions, certain sugar molecules or transport proteins glow and therefore become visible. Among other things, it is now possible to measure concentrations of sugar and understand how nutrients are transported from one cell to another. In order to determine the functions of individual genes, the scientists deliberately deactivate certain genes in various breeding lines of the same fly strain. Then they observe how these changes affect brain cells. “The jigsaw pieces gradually fit into place and form a complete picture,” says Stefanie Schirmeier.
Stefanie Schirmeier has already set her next target. Aided by her research team, she wants to develop a method which will enable her to look into the brains of living flies and observe how the brain’s metabolism evolves in the course of a fly’s life. This could make ageing processes visible and help scientists to understand how neurodegenerative disorders originate.