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Category: Holiday Specials

Valentine’s Day Special: Drosophila in lust

Valentine’s Day is quickly approaching, which means that men (and women) all over the U.S. are performing courtship rituals to woo a companion. But while we humans often have trouble figuring out the right moves to attract a potential mate, fruit flies have it down to a science. And incredibly, researchers can study fruit fly courtship to gain a better understanding of our own brains.

Fly courtshipThe fruit fly courtship ritual has a set of specific steps. Image modified from Greenspan and Ferveur, 2000.

In polite fruit fly society, males have the responsibility of wooing a female. The mating behavior is composed of several specific steps (see figure), which the males perform in repetition until the female responds (or until the male gives up trying). This courtship behavior is very well understood by researchers, due in part because the courtship ritual is so stereotyped and predictable. Courtship is a complex innate behavior, which means that all flies are born with the knowledge of how to do it. Successful mating means passing your genes on to the next generation, so the networks of neurons responsible for this behavior are critical for survival and therefore consistent among flies. This consistency provides a perfect system for studying how neurons interact to give rise to a behavior.

Fly researchers have made great progress in unraveling the anatomy underlying courtship, and found that the behavior arises from the integration of multiple sensory cues, including smell (is the female releasing “come and get me” pheromones?), vision (does the female look interested?), and touch (am I in the right spot?). The fruit fly brain has to combine all of this information to influence the fly’s decision making. Should he start the next step of the courtship ritual, or try this one again? Can he approach the female and try to mate?

“But who cares about fruit fly sex?” you might ask. The fly researchers studying courtship aren’t necessarily interested in exactly how flies get it on. They’re more interested in a general understanding of how the brain integrates multiple sensory cues to influence decisions. The fact that the “courtship circuit” is critical for survival suggests that it is also used by other important behaviors, and is shared by other species. Think about how much information needs to be integrated for you to hunt for food, drive a car, or even court another human. The complexity is amazing… how does our brain manage that?!  By first studying it in the simpler brains of fruit flies, we can gain a basic understanding that we can apply to our complex mammalian brains.

Studying courtship behavior can provide us with an understanding for how neurons communicate and integrate information to make decisions, but researchers can do even more with it. As our understanding of courtship increases, we can use it to investigate other behaviors that seem more directly related to human health, such as learning and memory, sleep, and addiction.

For example, the courtship ritual is most commonly used to study memory. Researchers have noticed that male flies tend to “give up” after too many rejections, so they’ve developed a learning experiment that exposes males to uninterested females. Normal males quickly learn to give up on trying to mate with them, but what happens if a scientist mutates a particular gene or “turns off” a certain molecule? Now researchers can use courtship to investigate the genes and molecules involved in learning and memory. If a mutant male never learns to stop courting, the gene might be involved in learning. If the mutant male initially learns to give up, but then quickly forgets the experience and tries again, the gene might be involved in long-term memory.

The predictable steps of courtship also allows researchers to easily recognize when a male is impaired in this innate behavior, providing a system for studying brain development. Last year, the Seghal lab published a study in which they used courtship behavior to show that sleep is necessary for normal brain development. They deprived young flies of sleep and found that, as adults, the flies were impaired in courtship. The impairment was due to lack of growth in a brain region important for the behavior, suggesting that sleep deprivation stunts brain development.

As a final example (and one of my favorites), in 2012 the Heberlein lab produced a paper showing that sexual rejection makes male flies turn to booze. Natural rewards such as sex activate the brain’s reward system, which is also activated by abused drugs and alcohol (did you know that flies can be alcoholics too?). Understanding how natural rewards, drugs, and rejections affect the reward system is important for treating or preventing addiction. From this study, the researchers in the Heberlein lab found that levels of neuropeptide F (NPF), a signaling chemical, rose and fell with reward and rejection. Low levels of NPF drove flies to drink, and artificially raising NPF levels prevented this behavior. Their finding that the same chemical is involved in both natural and artificial rewards directly helps research aimed at understanding a similar chemical in mammals called NPY.

In these research examples, the goal of studying courtship wasn’t to learn about fruit fly sex, it was to use what we know to answer more important questions. Because of these studies, researchers have identified dozens of genes and molecules involved in learning and memory, uncovered more reasons for why sleep is important, and progressed our understanding of how alcohol affects the brain. All of these findings have direct implications for human health because we also share those memory genes, need sleep, and use drugs and alcohol.

Flies in love

So the next time you see some flies getting it on near your bananas… swat them, because they’ll make hundreds of new nuisances for you to deal with. But afterward, you can smile knowingly to yourself and remember that scientists are studying the act to answer long-standing questions in neuroscience.

 

 

General references:

  • Pavlou H.J. and S.F. Goodwin (2013). Courtship behavior in Drosophila melanogaster: towards a ‘courtship connectome’, Current Opinion in Neurobiology, 23 (1) 76-83. DOI: http://dx.doi.org/10.1016/j.conb.2012.09.002
  • Griffith L.C. and A. Ejima (2009). Courtship learning in Drosophila melanogaster: Diverse plasticity of a reproductive behavior, Learning , 16 (12) 743-750. DOI: http://dx.doi.org/10.1101/lm.956309

New Year’s Special: Flies in Space (and other news from 2014)

Fruit fly researchers published thousands of papers in 2014, and several of them were picked up by the media. I even reviewed a couple of these popular stories on this blog. In April, the Seghal lab published a paper showing that sleep loss in young flies led to abnormal brain development and behavioral deficits in adulthood. In September, researchers in the Walker lab showed that increasing the levels of a molecule called AMPK in the guts of fruit flies could extend their lifespan, providing hope that we may one day be able to develop a pill to slow aging.

The most heartwarming story of 2014 came out in June, after a sixth-grader’s science fair project was published in the peer-reviewed journal PLoS One. Father and son worked together to discover that the artificial sweetener Truvia is toxic to fruit flies. Erythritol, the main ingredient of Truvia, is safe to consume for humans but quickly kills these winged pests. The researchers who worked on the project are now pursuing the possibility of using erythritol as a safe insecticide for fruit flies and other insects.

But perhaps the biggest news from 2014 involves flies… in space! Although many animals have been to space over the past several decades, fruit flies have recently proven to be ideal for studying the effects of zero gravity on earthly bodies. It’s widely known that microgravity (zero gravity) leads to rapid loss of bone density and muscle weakness, which is why astronauts spend a lot of time exercising while they’re in space. But did you know that microgravity also negatively affects the cardiovascular and immune systems? NASA recently announced a plan to send humans to Mars by 2030, but first, they need a better understanding of the long-term effects of microgravity on the body.

Fruit fly with fungusThis fruit fly is covered with a fungal infection after its immune system was compromised by 2 weeks in space. Image credit: Deborah Kimbrell/UC Davis

Space flies made the news in January 2014 after the results of a successful experiment were published in PLoS One by the Kimbrell lab. Researchers sent flies into space for 12 days to determine how zero gravity affects their immune system. It may seem like a short trip, but that’s about half the lifespan of your average fly (roughly the equivalent of sending a human into space for 40 years!). The researchers reported that flies subjected to microgravity had reduced ability to fight off a fungal infection compared to their earthbound brethren. Also interestingly, flies exposed to hypergravity (even stronger than Earth’s gravity) showed an increased ability to fight off the infection. The difference in immunity was caused by changes in the Toll pathway, an immune response which is also present in humans and other mammals. These promising results provided a leap forward in understanding how astronauts’ immune system may also be affected by microgravity.

Three more fruit fly experiments were launched into space in 2014. In April, a collaborative group led by Dr. Peter Lee sent flies into space for 30 days to study the effects of microgravity on the cardiovascular system (the experiment was named The HEART FLIES study). The second experiment was launched in September by a team at NASA’s Ames Research Center led by Dr. Sharmila Bhattacharya. The researchers hope to better understand how flies adapt to microgravity by studying changes in behavior.

The final experiment, launched in December 2014, was the maiden voyage of NASA’s newly-developed Fruit Fly Lab-01 project. NASA’s Fruit Fly Lab is a collaborative effort with a sophisticated set-up that researchers hope will improve our understanding of how spaceflight affects immune function. After 30 days in space, researchers will analyze the immune systems from three generations of flies exposed to various levels of gravity.

The results of these three missions should be published this year. Researchers at NASA are hoping that the findings will help them predict the physical challenges that astronauts will face during future space exploration, including the first human mission to Mars. NASA is also planning yearly sequels to their Fruit Fly Lab’s debut mission, so stay tuned!

References:

  • Baudier K.M., Nirali Patel, Katherine L. Diangelus, Sean O’Donnell & Daniel R. Marenda (2014). Erythritol, a Non-Nutritive Sugar Alcohol Sweetener and the Main Component of Truvia®, Is a Palatable Ingested Insecticide, PLoS ONE, 9 (6) e98949. DOI: http://dx.doi.org/10.1371/journal.pone.0098949
  • Taylor K., Michael D. George, Rachel Morgan, Tangi Smallwood, Ann S. Hammonds, Patrick M. Fuller, Perot Saelao, Jeff Alley, Charles A. Fuller & Deborah A. Kimbrell (2014). Toll Mediated Infection Response Is Altered by Gravity and Spaceflight in Drosophila, PLoS ONE, 9 (1) e86485. DOI: http://dx.doi.org/10.1371/journal.pone.0086485
  • NASA.gov

Christmas Special: Drosophila art

Happy Holidays!

Larval christmas tree
Green fluorescent protein (GFP) is expressed in motor neurons in the Drosophila melanogaster larval ventral ganglion. The larva is superimposed on an image of a starry night sky with the North star aligned at the top of the “tree”. The North star stays fixed in the night sky at this time of year, which inspired the tradition of stars on top of evergreen Christmas trees.
Image created by Dr. James Hodge
Image source Griffith lab

Thanksgiving Special: Uncovering the link between sleep and food

rest and digest turkey

If you ate a big Thanksgiving dinner yesterday, you probably felt drowsy and sluggish afterward, a phenomenon often referred to as a “food coma”. The belief that it’s caused by the tryptophan in turkey is a long busted myth, and in fact it can happen after any carb-heavy meal. The reasons for this post-food slump are relatively well understood from experiments in humans and other mammals. For one, big meals trigger a “rest and digest” response when the food reaches the stomach and small intestine (via activation of the parasympathetic nervous system). This diverts energy to digestion, making you feel sluggish and sleepy.  But wait, there’s more! Eating a meal full of carbs and other sugars also stimulates the release of insulin, which triggers a process to take up nutrients from the bloodstream. But a side effect of this process is an increase in the amount of serotonin and melatonin in the brain, two chemicals that are associated with drowsiness (and often happiness).

So having a full stomach makes you sleepy, but did you know that the relationship between sleep and food goes deeper than that? For example, studies in animals from fruit flies all the way to humans have shown that having an empty stomach can keep you awake. Even worse, chronic sleep deprivation stimulates appetite and can lead to weight gain. Studies in humans have uncovered strong correlations between sleep disorders like insomnia and obesity-related disorders such as diabetes and cardiovascular disease. One of the reasons for this is that sleep loss wreaks havoc on the levels of certain hormones, such as the “hunger hormone” ghrelin.

Thus, even though sleeping and eating are mutually exclusive behaviors (you can’t sleep while you’re eating), they’re also obviously connected. Both are essential for survival, so the brain may often be promoting at least one of them. But how does the brain decide which behavior is more important at any given time? When you’re hungry, it seems more important to stay awake and find food to prevent starvation, but sleep deprivation also has health consequences, so the brain needs to ensure you get enough sleep.

So how are sleep and hunger connected in the brain? Are they independent, so that hunger suppresses sleep, and sleepiness stimulates hunger? Or maybe they arise from the same mechanism, which signals in turn for either sleep or eating depending on your body’s needs. Answering this question will improve our understanding of sleep- and obesity-related disorders and how they’re linked, a necessary step before treatments can be developed.

Fruit flies make a great animal model for answering detailed questions like these, which take place on a molecular and cellular scale. Although much research has yet to be done, there have already been some informative findings. For starters, scientists have found that insulin-producing cells in the fly brain regulate both feeding and sleep, providing a cellular link between these two behaviors (remember that insulin’s activities are partially responsible for the food coma after Thanksgiving dinner). Their findings suggest that these cells integrate information from other brain regions about sleep need and hunger, and may even potentially act as a “behavioral switch” to signal which behavior is more important at any given time.

Other fruit fly researchers have found a link between eating and sleeping in a single molecule called “NPY-like short neuropeptide F” (sNPF). sNPF had already been shown to regulate food intake, but recently it was found that sNPF also promotes sleep. sNPF is similar to a mammalian chemical called “neuropeptide Y” (NPY), which also plays a little-understood role in sleep and eating in mammals. NPY has recently been studied as a possible drug target for obesity treatment in humans even though its role in other behaviors is unclear, so a better understanding of this chemical is essential to account for possible side effects such as sleep disruption.

Research in a variety of animal models (and humans) has shown us that sleep and hunger are related. Overall, the combined results of fruit fly research suggests that sleep and feeding behaviors may arise from shared mechanisms in the brain. Future studies will pin down the exact mechanisms and apply those findings to more complex mammalian systems. Hopefully, this research will lead to the development of drugs that can help with sleep- and obesity-related disorders. In the meantime, I think I’ll try drinking coffee with Thanksgiving dinner.

Happy Thanksgiving!

References:

Halloween Special: The Drosophila Halloween Genes

In the movies, spooks and phantoms are often undead humans with unfinished business. But would you be afraid of a ghostly fruit fly?

In 1995, fruit fly researchers Christiane Nüsslein-Volhard and Eric Wieschaus were awarded a Nobel Prize for their research on development. They were interested in understanding how a fertilized egg develops into a complex organism, and were the first to show that development was controlled by genes. In their famous paper published in 1980, they found a small number of genes that were important in determining the body plan and formation of body segments in fruit fly larva.

Four years later, the same researchers published a set of papers on a group of genes that caused developmental defects in fruit fly embryos. When a gene in this group was mutated, the embryos died before the exoskeleton was created. The mutations somehow disrupted the formation of the embryonic cuticle, the protective outer layer that should form around the embryo. The researchers (not without a sense of humor after long grueling hours in the lab) dubbed them the Halloween genes. The genes earned their name not just because they mutated and killed, but because the mutant embryos took on a ghostly appearance. This resulted in gene names such as disembodied, spook, spookier, shadow, shade, shroud, and phantom.

Phenotypes of two Halloween gene mutationsImages of the cuticles of a normal fruit fly embryo and two with mutations in a Halloween gene. Modified from Gilbert, 2004

So what do the Halloween genes do? Since the 1980s, researchers have discovered that all of the Halloween genes are cytochrome P450 (CYP) enzymes involved in synthesizing a steroid hormone called 20-hydroxyecdysone (20E) from cholesterol. 20E is required for metamorphosis and moulting in arthropods such as insects and crabs. As a result, disruption of 20E synthesis in fruit flies blocked formation of the exoskeleton in embryos. Hmm… I had to look all that up.

20E pathway involving Halloween genesThe Halloween genes encode enzymes that convert cholesterol into the arthropod steroid hormone 20E. Modified from Gilbert, 2008

CYP enzymes are found in most species and are involved in a very large variety of processes. In humans, they are involved in regulating hormones (among other things), including steroid hormones (just like in flies!). Steroid hormones are basically a group of steroids that act as hormones in the body, and they are synthesized from cholesterol (just like in flies!). Interestingly, testosterone and anabolic steroids, such as the ones that athletes may take, are actually steroid hormones. Thus, although mammals do not have 20E, they have other steroid hormones are important for development as well as reproduction, metabolism, and homeostasis, which allows cells to adapt to their changing environment. Because of these similarities, research in the Halloween genes may help us better understand how steroid hormones are synthesized in mammals.

Happy Halloween!

General References:

 

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