Tag Archives: Drosophila melanogaster

Why fruit flies can eat practically anything

They’re a common guest in our houses, and they could teach us a thing or two about our own food preferences.

Drosophila melanogaster — the common fruit fly. Image credits: André Karwath.

Fruit flies are particularly interesting to researchers as they serve as a simplified model for genetic research, and have provided numerous answers about how genes work.

Despite their names, fruit flies don’t necessarily need to munch on fruits. They often pop up around things like banana peel, but they can survive on pretty much anything — in biological terms, they’re called “nutritional generalists.” Another species which falls under the same nutritional umbrella is us humans. However, while our close relatives can also have varied diets, the evolutionary cousins of fruit flies are quite different — they’re nutritional specialists, and can only feed on specific plants.

There is a lot of debate in the scientific world about why animals (and sometimes animals in the same family) have such different nutritional tastes. A new study might shed some new light on this issue.

“Uncovering the differences in the molecular mechanisms between nutritional generalists and specialists can help us understand how organisms adapt to variable nutritional environments,” explain Kaori Watanabe and Yukako Hattori of Kyoto University, who led the study. “In our investigation, we changed the nutrient balance in the food of different Drosophila species and compared their nutritional adaptability along with their transcriptional and metabolic responses.”

To uncover the secrets of the fruit flies’ diet, researchers looked at their larva. They designed an experimental setup to see if the larvae can survive on three experimental diets: high protein, high carbohydrate, and protein-carbohydrate mix.

As expected, the generalists were able to survive on all the types of diets — but the specialist flies couldn’t survive in a carbohydrate-rich environment.

Researchers then tried to figure out why this was happening and came to the conclusion that the most likely culprit is a signaling molecule called TGF beta. TGF beta (or TGF-β) regulates a number of cellular functions, including cell growth and differentiation.

“A signaling pathway known as TGF-β/Activin signaling regulates the body’s response to carbohydrates. In the generalists, this pathway is quite flexible and maintains metabolic homeostasis under different diets. In fact, there are about 250 metabolic genes that are downregulated when their diet is carbohydrate-rich,” they explain.

Essentially, in specialist flies, the genes directing this pathway are more strongly expressed. This means they’re more efficient in deriving nutrients from some foods, but unable to derive enough from others — this increased efficiency comes at the expense of adaptability. Researchers believe that generalists retained their robust carbohydrate-responsive systems through genome-environment interactions, whereas the specialists lost them after living in low-carbohydrate environments.

It’s still early days, but since humans and flies share quite a few of these genes and signaling pathways, this paves the way for a comparative approach regarding the genetic variability of humans in response to dietary intakes.

The study has been published in Cell.

Yalenusresea

Drug cocktails can almost double lifespan — in worms and fruit flies, so far

A cocktail of drugs has been shown to effectively double lifespan — but so far, it only works for flies and worms.

Yalenusresea

Microscope image of Caenorhabditis elegans worms used in the study.
Image credits Jan Gruber.

One research team from Singapore wants to extend human lifespan through pharmacological means. It’s a lofty goal, but the results are already coming in. In a new study, the team reports they’ve successfully increased the healthy lifespan and delayed the rate of aging in a tiny little worm known as Caenorhabditis elegans. The study is the product of a collaboration between the Yale-NUS College, and the National University of Singapore (NUS).

Longer life for simple life

“Many countries in the world, including Singapore, are facing problems related to ageing populations,” said Dr. Gruber, an Assistant Professor of Biochemistry at Yale-NUS College, who lead the research effort.

“If we can find a way to extend healthy lifespan and delay ageing in people, we can counteract the detrimental effects of an ageing population, providing countries not only medical and economic benefits, but also a better quality of life for their people.”

Some widely-employed drugs have quite interesting effects beyond their primary indented use. For example, rapamycin/sirolimus, a drug administered following organ transplants to prevent organ rejection, has been shown to increase the lifespan of several simple (non-human) species. Gruber’s team wanted to see whether cocktails of such life-prolonging drugs could be more efficient at staving off old age than the sum of their individual components. They tested combinations of two or three compounds at a time. Drugs in each mix were selected to target a different metabolic pathway related to aging in C. elegans, a free-living roundworm that grows to around 1 mm (0.03 in) in length.

The first good sign is that the drugs didn’t have any negative impact on the worms’ health. The second good sign was that the cocktails were much more efficient than the individual compounds. For example, three-drug cocktails almost doubled the average lifespan of the worms. Needless to say, this is quite the achievement — no other drug intervention has ever had such an effect on lifespan in adult animals, the team reports.

The third and arguably most exciting finding is that treated worms were healthier and spent a larger part of their life in good health across all ages. So not only did they live more, but they lived better for a greater part of their lives compared to untreated worms. In collaboration with Associate Professor Nicholas Tolwinski (also at the Yale-NUS), the researchers found that the common fruit flies (Drosophila melanogaster) treated with the drug cocktails also had significantly increased lifespans.

The fact that the drugs worked in two organisms with distinct evolutionary backgrounds suggests that they work on ancient aging-related pathways. It’s likely, then, that they would work similarly in humans.

“We would benefit not only from having longer lives, but also spend more of those years free from age-related diseases like arthritis, cardiovascular disease, cancer, or Alzheimer’s disease,” Dr. Gruber said. “These diseases currently require very expensive treatments, so the economic benefits of being healthier for longer would be enormous.”

Dr. Gruber says that the research is just a proof-of-principle. It’s meant to show that the approach is viable, that a multiple-drug approach could be used to extend the healthy lifespan of adult animals — perhaps even humans.

In the future, the team plans to extend their research to cover three key areas. First, they want to develop drugs and drug mixes that are even more effective than the ones used in this study. They also want to determine exactly how each compound works to delay aging, in a bid to create computer models that can test quickly test many more potential drug combinations. Ultimately, they want to try and apply the findings in slowing down aging for humans.

The paper “Drug Synergy Slows Aging and Improves Healthspan through IGF and SREBP Lipid Signaling” has been published in the journal Developmental Cell.

Scientists image entire fly brain in ungodly detail

No fewer than 21 million images and 7,062 brain slices, all obtained using two high-speed electron microscopes — those are the results of the most detailed digital snapshot of the adult fruit fly brain.

Here (in color), reconstructed the neurons in the fly’s brain responsible for providing odor to a brain region involved in memory and learning. Image credits: Z. Zheng et al. / Cell.

For most of us, fruit flies (Drosophila melanogaster) are little more than a nuisance, buzzing around our over-ripe fruits. But for brain scientists, fruit flies provide an excellent model. Recently, a team of scientists at the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia, managed to map a fruit fly brain in unprecedented detail, identifying the individual synapses (junctions between neurons).

Essentially, they’ve created a visible neuronal roadmap, underpinning the web of connections that underpin specific fly behaviors.

“The entire fly brain has never been imaged before at this resolution that lets you see connections between neurons,” explains  Davi Bock, a group leader at Janelia who reported the work along with his colleagues on July 19, 2018, in the journal Cell.

“We think it will tell us something about how the animal learns – how it associates odors with a reward or punishment,” he explains.

The fruit fly has 100,000 neurons (for reference, humans have 100 billion). Each of those neurons branches out to reach other neurons, forming incredibly dense communication circuits.

Scientists can view these circuits, using a technique called serial section transmission electron microscopy. The technique, which has been developed for brain imaging but can also be applied to other fields, generates high-resolution three-dimensional images from small samples.

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Firstly, researchers dip the fly’s brain into a cocktail of heavy metals which mark the outline of each neuron, as well as its connections. Then, a small block of resin is prepared and ultrathin serial sections (100 nm thick) are cut using a specialized diamond “knife“. Some 7,000 slices are obtained.

The cuts are mounted on the block, where after further preparation, researchers hit the brain slices with a beam of electrons, which passes through everything except the metal-coated areas.

“It’s the same way that x-rays go through your body except where they hit bone,” Bock adds.

They used two electron microscopes which have a much higher resolution than conventional light microscopes.

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Traditionally, this process has been extremely slow. Everything had to be done by hand, and each photo had to be snapped individually. Imagine if you wanted to take 21 million photos — you’d be snapping for decades, Bock says. So he and his colleagues developed new tools to aid in this task, including two custom-built systems to rapidly move tissue samples in eight-micrometer increments, allowing them to quickly capture images of neighboring areas. With this, it only took seven minutes to image a brain slice — which is five times faster than the previous record. Engineers at Janelia also built a robotic loader that picks up and places samples automatically to help Bock’s team.

It’s remarkable how complex the fruit fly’s brain is, with so relatively few neurons.

“They can learn and remember. They know which places are safe and dangerous. They have elaborate sequences of courtship and grooming,” Bock explains.

For instance, Bock’s team followed a neuronal path that reaches out to the so-called mushroom body — a pair of structures in the brain of insects known to play a role in olfactory learning and memory. These cells have been described previously, but the new study allowed researchers to trace their outline more easily and confirm previous findings.

Moving on, there are many other neuronal pathways of interest which researchers will no doubt soon look into. Using the technical capabilities described in this new paper, it seems like researchers will able to move on to more human-like creatures, and that’s where things really start to get interesting.

The fruit fly brain dataset has been released and can be accessed and downloaded at temca2data.org. More than 20 lab groups are already working on the newly released dataset.

Journal Reference: Zheng et al.  “A complete electron microscopy volume of the brain of adult Drosophila melanogaster,” Cell. Published online July 19, 2018.

Personal Space Violation.

Scientists poke at the root of our need for personal space — using fruit flies

Feeling like people are invading your personal space? It’s dopamine that does it, researchers report.

Personal Space Violation.

Image credits Jeff Hitchcock / Flickr.

We’ve all been there. You’re having a chat with somebody one minute, and the next they’re simply too close. You didn’t make a conscious decision about this, didn’t settle on a ‘too near’ line, but you just know it’s being overrun at that exact moment. So you back away, almost by instinct.

You’d think we have a pretty good idea of what’s working in the background of a concept as universal as ‘personal space’ — but not really. That’s why a team led by Anne F. Simon of Western University’s Department of Biology started studying the need for social space and how it can be disrupted. They report that dopamine, a neurotransmitter best known for its role in the reward pathway of the brain, is a key substance in mediating social space.

A-buzz with dopamine

The team worked with Drosophila melanogaster, the common fruit fly, as they come with certain very desirable traits: they develop really fast, lay a lot of eggs, and are dirt-cheap to feed and care for. They’ve seen a lot of use in scientific pursuits, and they’re the insects Gregor Mendel used to lay the foundation of genetics.

Using genetic and pharmacological manipulations, the team tailored the neurons in some of the flies to produce more or less dopamine than those in unaltered fleas.

Their results show that dopamine is a key component in “the response to others in a social group, specifically, social spacing,” and could change how much space the flies need from each other. The effect was “prominent only in the day-time, and its effect varies depending on tissue, sex and type of manipulation.” For example, too little dopamine made male flies seek greater distances from each other, while too much dopamine made them close ranks. In female flies, both too much or too little release of dopamine made them increase social distance.

“Each animal has a preferred social bubble, a preferred personal space,” said Anne Simon.

“If we can connect the dots with other animals including humans — because we all have similar neurotransmitters — we may gain new ways of understanding what’s happening in some disorders where personal space can sometimes be an issue.”

That discovery may, in turn, have implications for better understanding conditions related to dopamine imbalances, such as schizophrenia or the autism spectrum, for example.

Next, the team plans to expand on the findings from the other way around, and find our how social cues influence dopamine release, and to identify the circuitry that regulates it.

“Ultimately, this research could lead us to understand a little better why some people are averse to social contact. It might also help us understand why some people who clearly want to interact don’t interpret some social cues the same way others might,” said Simon.

The paper “Modulation of social space by dopamine in Drosophila melanogaster, but no effect on the avoidance of the Drosophila stress odorant” has bee published in the journal Biology Letters.