Posts tagged fruit flies
Articles and news from the latest research reports.
Fruit flies may have more individuality and personality than we imagine.
And it might all be down to a bit of genetic shuffling in nerve cells that makes every fly brain unique, suggest Oxford University scientists.
Their new study has found that small genetic elements called ‘transposons’ are active in neurons in the fly brain. Transposons are also known as 'jumping genes', as these short scraps of DNA have the ability to move, cutting themselves out from one position in the genome and inserting themselves somewhere else.
The inherent randomness of the process is likely to make every fly brain unique, potentially providing behavioural individuality – or ‘fly personality’. So says Professor Scott Waddell, who led the work at the University of Oxford Centre for Neural Circuits and Behaviour: ‘We have known for some time that individual animals that are supposed to be genetically identical behave differently.
'The extensive variation between fly brains that this mechanism could generate might demystify why some behave while others misbehave,' he suggests.
The Oxford researchers, along with US colleagues at the University of Massachusetts Medical School and Howard Hughes Medical Institute, were able to deep-sequence the DNA from small numbers of nerve cells in the brains of Drosophila fruit flies.
They identified many transposons that were inserted in a number of important memory-related genes. Whether this is detrimental or advantageous to the fly remains an open question, the researchers say.
Scott Waddell notes that neural transposition has been described in rodent and human brains, and transposons have historically been considered to be problematic parasites. New insertions of transposons can on occasion disrupt genes (as was found in this study), and transposons have been associated to some human disorders such as schizophrenia.
However, it is also possible that organisms have harnessed transposition to generate variation within cells, and by extension create variation between individual animals that may turn out to be favourable.
Scott Waddell wants next to determine whether neural transposition provides an explanation for variation in fruit fly behaviour by finding ways of halting the process in flies in his lab.
Researchers Develop New System to Study Trigger of Cell Death in Nervous System
Researchers at the University of Arkansas have developed a new model system to study a receptor protein that controls cell death in both humans and fruit flies, a discovery that could lead to a better understanding of neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
Michael Lehmann, an associate professor of biological sciences, uses fruit fly genetics to study the receptor — N-methyl-D-aspartate receptor, known as the NMDA receptor — that triggers programmed cell death in the human nervous system.
With an aging population, neurodegenerative diseases have become a major public health concern, Lehmann said.
“Whenever brain cells die as a result of neurodegenerative disease, or as a consequence of injuries caused by stroke, exposure to alcohol or neurotoxins, this receptor is involved,” he said. “So it’s very important to understand how it functions and how it may be possible to influence it.”
When larvae of Drosophila melanogaster, a common fruit fly, grow from the larval stage into adults, they shed most of their former organs and grow new ones. About 1 ½ years ago, researchers in Lehmann’s laboratory discovered that the NMDA receptor is required for cell death in the system that they had used for several years to study basic mechanisms of programmed cell death in fruit flies.
“Our model system for studying programmed cell death is the salivary glands in the fly larvae, which are comparatively large organs that completely disappear during metamorphosis,” he said. “Disposal of this tissue by programmed cell death provides us with a very nice system to study the genes that are required for the process. We can use it to identify genes that are required for programmed cell death in humans, as well.”
The National Institutes of Health has awarded Lehmann a three-year, $260,530 grant to support the study.
Brandy Ree, a doctoral student in the interdisciplinary graduate program in cell and molecular biology, worked with Lehmann to use a combination of biochemistry and fruit fly genetics in an attempt to define the pathway that leads from activation of the receptor to the cell’s eventual death.
“We developed a new system to study the receptor outside the nervous system in a normal developmental context,” Lehmann said. “Many of the different components involved in cell death are known in this system. There are more than 30,000 publications about this receptor, but there is still very little known about how the receptor causes cell death. We just have to connect the dots and fit the receptor into the pathway to find out how exactly it contributes to the cell’s death.”
A mid-career investigator in the Center for Protein Structure and Function at the University of Arkansas, Lehmann has studied programmed cell death in Drosophila melanogaster for more than a decade.
In 2007, Lehmann’s research group discovered an important mechanism that regulates the destruction of larval fruit fly salivary glands that could point the way to understanding programmed cell death in the human immune system. They published their findings in the Journal of Cell Biology.
(Image: BD Biosciences)
Scientists identify brain’s ‘molecular memory switch’
Scientists have identified a key molecule responsible for triggering the chemical processes in our brain linked to our formation of memories. The findings, published in the journal Frontiers in Neural Circuits, reveal a new target for therapeutic interventions to reverse the devastating effects of memory loss.
The BBSRC-funded research, led by scientists at the University of Bristol, aimed to better understand the mechanisms that enable us to form memories by studying the molecular changes in the hippocampus — the part of the brain involved in learning.
Previous studies have shown that our ability to learn and form memories is due to an increase in synaptic communication called Long Term Potentiation [LTP]. This communication is initiated through a chemical process triggered by calcium entering brain cells and activating a key enzyme called ‘Ca2+ responsive kinase’ [CaMKII]. Once this protein is activated by calcium it triggers a switch in its own activity enabling it to remain active even after the calcium has gone. This special ability of CaMKII to maintain its own activity has been termed ‘the molecular memory switch’.
Until now, the question still remained as to what triggers this chemical process in our brain that allows us to learn and form long-term memories. The research team, comprising scientists from the University’s School of Physiology and Pharmacology, conducted experiments using the common fruit fly [Drosophila] to analyse and identify the molecular mechanisms behind this switch. Using advanced molecular genetic techniques that allowed them to temporarily inhibit the flies’ memory the team were able to identify a gene called CASK as the synaptic molecule regulating this ‘memory switch’.
Dr James Hodge, the study’s lead author, said: “Fruit flies are remarkably compatible for this type of study as they possess similar neuronal function and neural responses to humans. Although small they are very smart, for instance, they can land on the ceiling and detect that the fruit in your fruit bowl has gone off before you can.”
“In experiments whereby we tested the flies’ learning and memory ability, involving two odours presented to the flies with one associated with a mild shock, we found that around 90 per cent were able to learn the correct choice remembering to avoid the odour associated with the shock. Five lessons of the odour with punishment made the fly remember to avoid that odour for between 24 hours and a week, which is a long time for an insect that only lives a couple of months.“
By localising the function of the key molecules CASK and CaMKII to the flies’ equivalent brain area to the human hippocampus, the team found that the flies lacking these genes showed disrupted memory formation. In repeat memory tests those lacking these key genes were shown to have no ability to remember at three hours (mid-term memory) and 24 hours (long-term memory) although their initial learning or short-term memory wasn’t affected.
Finally, the team introduced a copy of the human CASK gene — it is 80 per cent identical to the fly CASK gene — into the genome of a fly that completely lacked its own CASK gene and was therefore not usually able to remember. The researchers found that flies which had a copy of the human CASK gene could remember like a normal wildtype fly.
Dr Hodge, from the University’s School of Physiology and Pharmacology, said: “Research into memory is particularly important as it gives us our sense of identity, and deficits in learning and memory occur in many diseases, injuries and during aging”.
“CASK’s control of CaMKII ‘molecular memory switch’ is clearly a critical step in how memories are written into neurons in the brain. These findings not only pave the way for to developing new therapies which reverse the effects of memory loss but also prove the compatibility of Drosophila to model these diseases in the lab and screen for new drugs to treat these diseases. Furthermore, this work provides an important insight into how brains have evolved their huge capacity to acquire and store information.”
These findings clearly demonstrate that neuronal function of CASK is conserved between flies and human, validating the use of Drosophila to understand CASK function in both the healthy and diseased brain. Mutations in human CASK gene have been associated with neurological and cognitive defects including severe learning difficulties.
(Source: bristol.ac.uk)
Nerve regeneration research and therapy may get boost from new discovery
A new mechanism for guiding the growth of nerves that involves cell-death machinery has been found by scientists at the University of Nevada, Reno that may bring advances in neurological medicine and research. The team obtained the evidence in studies of fruit flies and reported their discovery in an article published in the prestigious science publication Cell Reports.
"Although the fly is a relatively simple organism, almost every gene identified in this species appears to be carrying out similar functions in humans," said Thomas Kidd, associate professor in the University’s biology department in whose lab the work was performed.
The Kidd lab is part of a $10 million Center for Biomedical Research Excellence Project in Cell Biology of Signaling at the University, which is funded by the National Institute of Health’s Institute of General Medical Sciences. The project is also funded by the National Science Foundation.
"Flies are useful because the neural mechanisms we are studying are similar to those in mammals," said Gunnar Newquist, lead author of the Cell Reports article and a post-doctoral neuroscience researcher in Kidd’s lab. "We’ve found something no one has seen before, that blocking the cell-death pathway can make nerves deprived of guidance cues figure out the right way to connect with other neurons. This was completely unexpected and novel, but really exciting because it changes the way we look at nerve growth.
"Neurons have a natural ability to die, if they fail to make the right connections they usually die. Neurons, like most other cell types, have the capacity to commit suicide and many do so during the formation of the nervous system."
The wiring of nervous systems is composed of axons, specialized extensions of neurons that transmit electrical impulses. During development axons navigate long distances to their targets by using signals in their environment. Netrin-B is one of those signals. Kidd, Newquist and colleagues have shown that Netrin-B also keeps neurons alive.
"Take away the Netrin-B and growth and cell death goes haywire," Newquist said.
This led them to the discovery that the cell-death machinery is active in growing nerves, and appears to be an integral part of the navigation mechanism.
"We use fruit fly genetics to study how these axons navigate these long distances correctly when developing," Kidd said. "Understanding the mechanisms they use to navigate is of great interest, not only for understanding how our brains form, but also as a starting point to devise ways to stimulate the re-growth of axons after injury, especially spinal cord injuries.
"Our work suggests that therapeutics designed to keep neurons alive after injury may be able to stimulate neurons to start re-growing or sprouting new connections."
"I am very pleased to see Tom’s and Gunnar’s hard work come to fruition," said Chris von Bartheld, director of the University’s cell-biology COBRE and a professor in the University of Nevada School of Medicine. "Linking axonal path finding and cell death signaling opens exciting new venues to better understand both topics. It also shows that our recently established center in cell biology is achieving its goals of producing top-level biomedical research."
(Source: unr.edu)
Highly developed antennae containing different types of olfactory receptors allow insects to use minute amounts of odors for orientation towards resources like food, oviposition sites or mates. Scientists at the Max Planck Institute for Chemical Ecology in Jena, Germany, have now used mutant flies and for the first time provided experimental proof that the extremely sensitive olfactory system of fruit flies − they are able to detect a few thousand odour molecules per millilitre of air, whereas humans need hundreds of millions − is based on self-regulation of odorant receptors. Even fewer molecules below the response threshold are sufficient to amplify the sensitivity of the receptors, and binding of molecules shortly afterwards triggers the opening of an ion channel that controls the fly’s reaction and flight behaviour. This means that a below threshold odor stimulation increases the sensitivity of the receptor, and if a second odour pulse arrives within a certain time span, a neural response will be elicited.
It is amazing how many fruit flies (Drosophila melanogaster) find their way to a rotting apple. It is known that insects are able to detect the slightest concentrations of odour molecules, especially pheromones, but also “food signals”.
Dieter Wicher, Shannon Olsson, Bill Hansson and their colleagues at the Max Planck Institute for Chemical Ecology were looking for answers to the question why insects can trace odour molecules so easily and at such low concentrations in comparison to other animals. They focused their attention on odorant receptor proteins in the antenna, the insects’ nose. These insect proteins are pretty young from an evolutionary perspective and their molecular constituents may be the basis for the insects’ highly sensitive sense of smell.
Insect odorant receptors form a receptor system that consists of the actual receptor protein and an ion channel. After binding of an odour molecule, receptor protein and ion channel trigger the neural electrical response. This mechanism was recently described in the receptor system Or22a-Orco. Apart from functioning as so-called ionotropic receptors, which enable ion flow through membranes after binding of odour molecules, odorant receptors also elicit intracellular signals. These stimulate the formation of cyclic adenosine monophosphate (cyclic AMP or cAMP), which activates an ion flow through the co-receptor Orco. The role and relevance of this weak and slow electrical current, however, was until now unclear.
Merid N. Getahun, a PhD student from Ethiopia, and his colleagues have conducted numerous experiments on Drosophila olfactory neurons. They injected tiny amounts of compounds that stimulate, inhibit or imitate cAMP formation directly into the sensory hairs housing olfactory sensory neurons on the fly antenna. The researchers tested the flies’ responses to ethyl butyrate, which has a fruity odour similar to pineapple, and measured activity in the sensory neurons by using glass microelectrodes. As a control, they used genetically modified fruit flies where the co-receptor Orco had been inactivated. “The fact that these mutants are no more able to respond to cAMP or the inhibition/activation of the involved key enzymes, such as protein kinase C and phospholipase C, shows that the highly sensitive olfactory system in insects is regulated intracellularly by their own odorant receptors,” says Dieter Wicher, the leader of the research group.
The combination of odorant receptor and co-receptor Orco can be compared to a transistor, Wicher continues: A weak basic current is sufficient to release the main electric current that activates the neuron. The process can also be seen as a short-term memory situated in the insect nose. A very weak stimulus does not elicit a response when it first occurs, but if it reoccurs within a certain time span it will release the electrical response according to the principle “one time is no time, but two is a bunch.”
When food is scarce, a smaller brain will do
A new study explains how young brains are protected when nutrition is poor. The findings, published on March 7th in Cell Reports, a Cell Press publication, reveal a coping strategy for producing a fully functional, if smaller, brain. The discovery, which was made in larval flies, shows the brain as an incredibly adaptable organ and may have implications for understanding the developing human brain as well, the researchers say.
The key is a carefully timed developmental system that ultimately ensures neural diversity at the expense of neural numbers.
"In essence, this study reveals an adaptive strategy allowing the reduction of the number of neurons produced in the face of sub-optimal nutritional conditions, while preserving their diversity," said Cedric Maurange of Aix-Marseille Université in France. "This is a survival strategy permitting the developing brain to produce the minimal set of neurons necessary to be functional, at the minimum energetic cost."
Most of the neurons in the human brain are produced well before birth, as the developing fetus grows and changes in the womb. But how the young brain copes with adversity is an unresolved question. If a mother doesn’t have enough food to eat, what happens to the brain of her baby?
To find out, Maurange and his colleagues looked to the fruit fly, a workhorse of biology. The much shorter lifespan of fruit flies means that they reach the equivalent of toddlerhood in just four days’ time.
Their developmental studies in the fly visual system reveal an early sensitivity to the availability of amino acids, ingredients that are the building blocks of proteins. They found that a fly with all the amino acids it needs ends up with a larger pool of neural stem cells than one lacking those nutrients. Later, when those neural stem cells start to produce the many different types of neurons, that nutrient sensitivity goes away. The end result is a brain that is functional but smaller. In some flies, the optic lobe contained 40 percent fewer neurons and still worked.
"We were surprised to realize that the optic lobe can have such a drastically reduced number of neurons under dietary restriction and yet remains functional," Maurange said.
The findings may help to explain well-documented patterns of brain growth in humans. The human brain is protected over other organs when nutrients are lacking late in fetal development, producing a brain that is large relative to organs such as the pancreas or intestine. But when nutrients are limited early in larval development, the brain remains small along with the rest of the body. Those growth patterns are known as asymmetric and symmetric intrauterine growth restriction (IUGR), respectively.
"Our work suggests new avenues to investigate how early nutrient restriction affects mammalian brain development and may help in understanding the mechanisms underlying symmetric and asymmetric IUGR in humans," Maurange said.
Molecular ‘Two-Way Radio’ Directs Nerve Cell Branching And Connectivity
Working with fruit flies, Johns Hopkins scientists have decoded the activity of protein signals that let certain nerve cells know when and where to branch so that they reach and connect to their correct muscle targets. The proteins’ mammalian counterparts are known to have signaling roles in immunity, nervous system and heart development, and tumor progression, suggesting broad implications for human disease research. A report of the research was published online Nov. 21 in the journal Neuron.
To control muscle movements, fruit flies, like other animals, have a set of nerve cells called motor neurons that connect muscle fibers to the nerve cord, a structure similar to the spinal cord, which in turn connects to the brain. During embryonic development, the nerve cells send wire-like projections, or axons, from the nerve cord structure out to their targets. Initially, multiple axons travel together in a convoy, but as they move forward, some axons must exit the “highway” at specific points to reach particular targets.
In their experiments, the researchers learned that axons travelling together have proteins on their surfaces that act like two-way radios, allowing the axons to communicate with each other and coordinate their travel patterns, thus ensuring that every muscle fiber gets connected to a nerve cell. “When axons fail to branch, or when they branch too early and too often, fruits flies, and presumably other animals, can be left without crucial muscle-nerve connections,” says Alex Kolodkin, Ph.D., a Howard Hughes investigator and professor of neuroscience at the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine.
At the center of the communications system, Kolodkin says, is a protein called Sema-1a, already known to reside on the surface of motor neuron axons. If a neighboring axon has a different protein, called PlexA, on its surface, it will be repulsed by Sema-1a and will turn away from the axon bundle. So Sema-1a acts as an instructional signal and PlexA as its receptor. In the fruit fly study, the scientists discovered that Sema-1a can also act as a receptor for PlexA. “We used to think that this pair of surface proteins acted as a one-way radio, with information flowing in a single direction,” says Kolodkin. “What we found is that instructional information flows both ways.”
The Johns Hopkins team identified the “two-way” system by knocking out and otherwise manipulating fruit fly genes and then watching what happened to motor neuron branching. In these experiments, the researchers uncovered still other proteins located within the motor axons that Sema-1a interacts with after receiving a PlexA signal. When the gene for a protein called Pebble was deleted, for example, motor axons bunched together and didn’t branch. When the gene for RhoGAPp190 was deleted, motor axons branched too soon and failed to recognize their target muscles.
Through a series of biochemical tests, Kolodkin’s team found that Pebble and RhoGAPp190 both act on a third protein, Rho1. When Rho1 is activated, it collapses the supporting structures within an axon, making it “limp” and unable to continue toward a target. Sema-1a can bind to Pebble or to RhoGAPp190, and subsequently, these proteins can bind to Rho1. Binding to Pebble activates Rho1, causing axons to branch away from each other. However, binding to RhoGAPp190 shuts down Rho1, causing axons to remain bunched together. Thus, says Kolodkin, balance in the amounts of available Pebble and RhoGAPp190 can determine axon behavior, although what determines this balance is still unknown.
“This signaling is complex and we still don’t understand how it’s all controlled, but we’re one step closer now,” says Kolodkin. He notes that “a relative” of the Sema-1a protein in humans has already been implicated in schizophrenia, although details of this protein’s role in disease remain unclear. “Our experiments affirm how important this protein is to study and understand,” adds Kolodkin.
Mechanism of hearing is similar to car battery
University of Iowa biologist Daniel Eberl and his colleagues have shown that one of the mechanisms involved in hearing is similar to the battery in your car.
And if that isn’t interesting enough, the UI scientists advanced their knowledge of human hearing by studying a similar auditory system in fruit flies—and by making use of the fruit fly “love song.”
To see how the mechanism of hearing resembles a battery, you need to know that the auditory system of the fruit fly contains a protein that functions as a sodium/potassium pump, often called the sodium pump for short, and is highly expressed in a specialized support cell called the scolopale cell.
The scolopale cell is important because it wraps around the sensory endings in the fly’s ear and makes a tight extra-cellular cavity or compartment around them called the scolopale space.
“You could think of these compartments as similar to the compartments of a battery that need to be charged up so they can drive electrons through circuits,” says Eberl, whose paper made the cover of the journal Proceedings of the National Academy of Sciences. “In the auditory system, the charge in the scolopale space drives ions, or electrically charged atoms, through membrane channels in the sensory endings that open briefly in response to activation by sounds.
“Our work shows that the sodium pump plays a particularly important role in this cell to help replenish or recharge this compartment with the right ions. The human ear also relies on a compartment called the scala media, which similarly drives ions into the sensory cells of the ear,” he says.
How was the research done? This is where the fruit fly love song comes into play.
Testing whether or not a fruit fly can hear the love song—a sound generated by a vibrating wing—enables Eberl to learn whether electrical recharging is occurring in the fly ear. The fruit fly love song played a role in the research by stimulating the fly to move whenever a sound was emitted and received.
“In these experiments we tested the fly’s hearing by inserting tiny electrodes in the fly’s antenna, then measuring the electrical responses when we play back computer-generated love songs,” he says.
Eberl notes there are many similarities between fruit fly and human mechanisms of hearing. That means his work on the fly model to identify additional new components required for generating the correct ion balance in the ear will help scientists to understand the human process in more detail.
In an article published online this week in the journal Nature, the UCSF team has identified the exact subset of nerve cells responsible for communicating gentle touch to the brains of Drosophila larvae—called class III neurons. They also uncovered a particular protein called NOMPC, which is found abundantly at the spiky ends of the nerves and appears to be critical for sensing gentle touch in flies.Without this key molecule, the team discovered, flies are insensitive to any amount of eyelash stroking, and if NOMPC is inserted into neurons that cannot sense gentle touch, those neurons gain the ability to do so.
“NOMPC is sufficient to confer sensitivity to gentle touch,” said Yuh Nung Jan, PhD, a professor of physiology, biochemistry and biophysics and a Howard Hughes Medical Institute investigator at UCSF. Jan led the study with his wife Lily Jan, PhD, who is also a UCSF professor and a Howard Hughes Medical Institute investigator.
The work sheds light on a poorly understood yet fundamental sense through which humans experience the world and derive pleasure and comfort.
Why is Touch Still Such a Mystery?
Scientists generally feel that, like those other senses, the sense of touch is governed by peripheral nerve fibers stretching from the spine to nerve endings all over the body. Special molecules in these nerve endings detect the mechanical movement of the skin surrounding them when it is touched, and they respond by opening and allowing ions to rush in. The nerve cell registers this response, and if the signal is strong enough, it will fire, signaling the gentle touch to the brain.
What has been missing from the picture, however, are the details of this process. The new finding is a milestone in that it defines the exact nerves and uncovers the identity of the NOMPC channel, one of the major molecular players involved—at least in flies.
Jan and his colleagues made this discovery through an unusual route. They were looking at the basic physiology of the developing fruit fly, examining how class III neurons develop in larvae. They noticed that when these cells developed in the insects, their nerve endings would always become branches into spiky “dendrites.”
Wanting to know what these neurons are responsible for, they examined them closely and found the protein NOMPC was abundant at the spiky ends. They then examined a fly genetically engineered to have a non-functioning form of NOMPC and showed that it was insensitive to gentle touch. They also showed that they could induce touch sensitivity in neurons that do not normally respond to gentle touch by inserting copies of the NOMPC protein into them.
(Image: Dietrich Meyer)
Brain May ‘See’ More Than the Eyes, Study Indicates
Vision may be less important to “seeing” than is the brain’s ability to process points of light into complex images, according to a new study of the fruit fly visual system currently published in the online journal Nature Communications.
University of Virginia researchers have found that the very simple eyes of fruit fly larvae, with only 24 total photoreceptors (the human eye contains more than 125 million), provide just enough light or visual input to allow the animal’s relatively large brain to assemble that input into images.
“It blows open how we think about vision,” said Barry Condron, a neurobiologist in U.Va.’s College of Arts & Sciences, who oversaw the study. “This tells us that visual input may not be as important to sight as the brain working behind it. In this case, the brain apparently is able to compensate for the minimal visual input.”
Condron’s graduate students, Elizabeth Daubert, Nick Macedonia and Catherine Hamilton, conducted a series of experiments to test the vision of fruit fly larvae after they noticed an interesting behavior of the animals during a different study of the nervous system. They found that when a larva was tethered to the bottom of a petri dish, other larvae were attracted to it as it wiggled attempting to free itself.
The animals apparently saw the writhing motion and were attracted to it, willingly traveling toward it. After several further experiments to understand how they sensed the motion, the researchers learned that the nearly blind animals likely were seeing the action, by wagging their heads side-to-side in a scanning motion to detect it, rather than by only hearing it or feeling vibration or by smelling the trapped larva. This was a surprise because of the very simple and limited vision of fruit fly larvae.