A how-to manual for fruit fly research has been created

The first ever basic training package to teach students and scientists how to best use the fruit fly, Drosophila, for research has been published. It’s hoped it will encourage more researchers working on a range of conditions from cancer to Alzheimer’s disease to use the humble fly.

The unique scheme has been put together by Dr Andreas Prokop from the Faculty of Life Sciences at the University of Manchester and John Roote from the Department of Genetics at the University of Cambridge.

John Roote said, “In 1910 Thomas Hunt Morgan isolated the first Drosophila sex-linked mutation, white.  Since then many thousands of research workers have realised the potential of the humble fruit fly.

“The powerful research tools that we have today combined with a century of background knowledge, the vast collections of stocks that are available to everyone and the fortuitous ‘pre-adaptation’ of the fly for life in a laboratory ensure that Drosophila melanogaster maintains its position as the pre-eminent model organism for research in genetics.  However, until now a comprehensive teaching programme to guide students through the often daunting first few steps has been surprisingly absent.”

Dr Prokop said: “People don’t realise just how useful the tiny fruit fly can be when it comes to research. Fellow scientists are often not aware of their genetic value for research. For example, about 75% of known human disease genes have a recognisable match in the genome of fruit flies which means they can be used to study the fundamental biology behind complex conditions such as epilepsy or neurodegeneration.”

Fruit flies have been used for scientific research for more than a hundred years. They have allowed scientific breakthroughs in genetics, body structure and function. The first jet lag gene and the first learning gene were identified in flies as well as breakthroughs in neuroscience, such as the discovery of the first channel proteins.

Training package: How to design a genetic mating scheme: a basic training package for Drosophila genetics

A direct line through the brain to avoid rotten food

Consuming putrid food can be lethal as it allows bacterial pathogens to enter the digestive system. To detect signs of decay and thus allowing us and other animals to avoid such food poisoning is one of the main tasks of the sense of smell. Behavioural scientists and neurobiologists at the Max Planck Institute for Chemical Ecology in Jena, Germany, have now for the first time decoded the neural mechanisms underlying an escape reflex in fruit flies (Drosophila) activated in order to avoid eating and laying eggs in food infected by toxic microorganisms. A super-sensitive and completely dedicated neural line, from olfactory receptor, via sensory neuron and primary brain neurons, is activated as soon as the tiniest amount of geosmin is in the air. Geosmin is a substance released by bacteria and mold fungi toxic to the fly. This stimulus overrides all other food odour signals, irrespective of how attractive they are on their own. Consequently, geosmin is a full STOP signal that prevents flies from eating and laying eggs in toxic food, similar to when we open the fridge and smell last week’s forgotten dinner.

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How Cells in the Nose Detect Odors

Now a team of scientists, led by neurobiologists at the University of California, Riverside, has an explanation. Focusing on the olfactory receptor for detecting carbon dioxide in Drosophila (fruit fly), the researchers identified a large multi-protein complex in olfactory neurons, called MMB/dREAM, that plays a major role in selecting the carbon dioxide receptors to be expressed in appropriate neurons.

Study results appear in the Nov. 15 issue of Genes & Development.  The research is featured on the cover of the issue.

According to the researchers, a molecular mechanism first blocks the expression of most olfactory receptor genes (~60) in the fly’s antennae. This mechanism, which acts like a brake, relies on repressive histones —proteins that tightly wrap DNA around them. All insects and mammals are equipped with this mechanism, which keeps the large families of olfactory receptor genes repressed.

“How, then, do you release this brake so that only the carbon dioxide receptor is expressed in the carbon dioxide neuron while the remaining receptors are repressed?” said Anandasankar Ray, an assistant professor of entomology, whose lab conducted the research. “Our lab, in collaboration with a lab at Stanford University, has found that the MMB/dREAM multi-protein complex can act on the genes of the carbon dioxide receptors and de-repress the braking mechanism — akin to taking the foot off the brake pedal. This allows these neurons to express the receptors and respond to carbon dioxide.”

Ray explained that one way to understand the mechanism in operation is to consider a typewriter. When none of the keys are pressed, a spring mechanism or “brake” can be imagined to hold the type bars away from the paper. When a key is pressed, however, the brake on that key is overcome and the appropriate letter is typed onto the paper. And just as typing only one letter in one spot is important for each letter to be recognized, expressing one receptor in one neuron lets different sensor types to be generated in the nose.

The Fabric for Weaving Memory

The details of memory formation are still largely unknown. It has, however, been established that the two kinds of memory – long term and short term – use different mechanisms. When short-term memory is formed, certain proteins in the nerve cells (neurons) of the brain are transiently modified. To establish long-term memory, the cells have to synthesize new protein molecules. This has been shown in experiments with animals. When drugs were used to block protein synthesis, the treated animals were not able to form long-term memory.

The precise mechanism by which the newly synthesized proteins regulate memory formation is still poorly understood. They are thought to strengthen existing connections between neurons, as well as establish new connections. Both processes are required for long-term memory formation.

A nerve cell in the brain makes connections with tens of thousands of other nerve cells through so-called synapses. When memory is formed, only specific synapses, which are activated by a specific experience are modified. The mechanism of how the synthesis of new proteins can be restricted to these activated synapses has been unclear. Neurobiologists have postulated the existence of “synaptic tags”. One of the candidates is a family of proteins known to regulate local protein synthesis, the CPEB family of proteins. These proteins have been known for some time to perform important tasks during embryonic development, and recently have been identified in neuronal synapses.

In 2007, Krystyna Keleman, a neuroscientist at the Research Institute of Molecular Pathology (IMP) in Vienna, was able to show that fruit flies require CPEB proteins for long-term memory formation.

To study memory formation, the researchers at the IMP looked at the sexual behavior of flies. After copulation, female flies loose interest in the courtship advances of males. Male flies must learn – by trial and error – that only virgin females are receptive. The key to telling them apart is their smell.

Fruit flies’ eyes shrink a little to see

I spy, with my mechanical eye. It seems a simple mechanical change plays a role in sensory perception in fruit flies, and possibly in many other animals, including humans.

The eyes of the common fruit fly (Drosophila melanogaster) contain clusters of light-sensitive cells organised into rods. When light strikes one of these cells, it triggers a series of chemical reactions. These cause a protein called a transient receptor potential (TRP) ion channel to open. When it’s open, the TRP allows charged particles to flow into the cell, causing the cell to send a signal to the fly’s brain.

TRP channels play a part in sensory perception in many animals, from nematodes to humans. But nobody knew how the chemical signals make the TRP channel open.

Mechanisms Underlying Childhood Neuromuscular Disease Found

A study by scientists from the Motor Neuron Center at Columbia University Medical Center (CUMC) suggests that spinal muscular atrophy (SMA), a genetic neuromuscular disease in infants and children, results primarily from motor circuit dysfunction, not motor neuron or muscle cell dysfunction, as is commonly thought. In a second study, the researchers identified the molecular pathway in SMA that leads to problems with motor function. Findings from the studies, conducted in fruit fly, zebrafish and mouse models of SMA, could lead to therapies for this debilitating and often fatal neuromuscular disease. Both studies were published today in the online edition of the journal Cell (1, 2).

“Scientists call SMA a motor neuron disease, and there is post-mortem evidence that it does cause motor neurons to die,” said Brian McCabe, PhD, assistant professor of pathology and cell biology and of neuroscience in the Motor Neuron Center, who led the first study. “However, it was not clear whether the death of motor neurons is a cause of the disease or an effect. Our findings in the fruit fly SMA model show that the disease originates in other motor circuit neurons, which then causes motor neurons to malfunction.”

In motor circuits, which coordinate muscle movement, specialized sensory neurons called proprioceptive neurons pick up and relay information to the spinal cord and brain about the body’s position in space. The central nervous system then processes and relays the signals, including via interneurons, to motor neurons, which in turn stimulate muscle movement.

“To our knowledge, this is the first clear demonstration in a model organism that defects in the function of a neuronal circuit are the cause of a neurological disease,” added Dr. McCabe.

Engineered flies spill secret of seizures

In a newly reported set of experiments that show the value of a particularly precise but difficult genetic engineering technique, researchers at Brown University and the University of California–Irvine have created a Drosophila fruit fly model of epilepsy to discern the mechanism by which temperature-dependent seizures happen.

The researchers used a technique called homologous recombination — a more precise and sophisticated technique than transgenic gene engineering — to give flies a disease-causing mutation that is a direct analogue of the mutation that leads to febrile epileptic seizures in humans. They observed the temperature-dependent seizures in whole flies and also observed the process in their brains. What they discovered is that the mutation leads to a breakdown in the ability of certain cells that normally inhibit brain overactivity to properly regulate their electrochemical behavior.

In addition to providing insight into the neurology of febrile seizures, said Robert Reenan, professor of biology at Brown and a co-corresponding author of the paper in the Journal of Neuroscience, the study establishes

“This is the first time anyone has introduced a human disease-causing mutation overtly into the same gene that flies possess,” Reenan said.

What Drives Your Daily Biological Clock?

Researchers working with fruit flies say they have discovered one way that the body’s biological clock controls brain-cell activity that influences daily rhythms.

They believe their findings might improve understanding about sleep-wake cycles and lead to new treatments for sleep disorders and jet lag.

"The findings answer a significant question: how biological clocks drive the activity of clock neurons, which, in turn, regulate behavioral rhythms," study senior author Justin Blau, associate professor in New York University’s department of biology, said in a university news release.

Previous research with fruit flies’ “clock genes” led to the discovery of similar genes in humans, according to the news release.

It was known that biological clocks control neuronal activity, but it wasn’t known how information from biological clocks drives rhythms in the electrical activity of pacemaker neurons that control daily rhythms.

The NYU team looked at pacemaker neurons in the central brain of fruit flies that set the timing of the daily transitions between sleep and wake. They isolated these neurons and identified sets of genes with different levels of activity at dawn and dusk.

Follow-up experiments found that the activity of a gene called Ir was much higher at dusk than at dawn and that it was more active in the pacemaker neurons than in the rest of the brain. The researchers also found that increasing or decreasing levels of Ir affected behavioral rhythms and changed the timing and strength of variations in the core clock.

"We were looking for an output of the biological clock that would link the core clock to neuronal activity," Blau said. "Ir seems to do this, but it also, remarkably, feeds back to regulate the core clock itself. Feedback loops seem to be deeply engrained into the biological clock and presumably help these clocks work so well."

The study was published in the October issue of the Journal of Biological Rhythms. Researchers have noted that results from animal studies do not necessarily translate to humans.