Tag Archives: c. elegans

c. elegans nematode brain activity

What a worm’s brain looks like fired up

These aren’t Christmas lights, but the actual neural activity of Caenorhabditis Elegans, a parasitic nematode. The brain imaging was done by researchers at Princeton University, and no worm had to be cut open. Instead, the researchers used a special protein which  fluoresces in response to calcium.

c. elegans nematode brain activity

When scientists tap the brain, they’re looking for one prime indicator: electrical activity. When a neuron is active, it fires an action potential which is basically a depolarization made between a neuron’s axon to another neuron it signals to. Now, traditionally neuroscientists use a technique called electrophysiology to study the patterns of neuron electrical activity. It’s precise, yet the analysis is limited to a handful of neurons at a time. A more interesting method exploits the fact that when a neuron is active (again, depolarized), calcium flows into it. Using special dyes (proteins) that fluoresce in response to whether or not they bind to calcium, scientists can monitor these calcium dynamics and in turn the depolarization.

That’s exactly what the Princeton researchers achieved, allowing them to monitor in real time  77 of the nematode’s 302 neurons as they light up. These have been shared in this amazing video, split into four frames. In the upper left, we see the location of the neurons, while the upper right shows a simulation of the calcium signaling which is analogous to neural electrical patterns. In the lower two panels we zoom out: the worm itself (left) and the location of the brain (right).

Using this data, the researchers would like to devise a mathematical model that will allow them to simulate and control the worm’s brain. Previously, other efforts identified how C. elegans can identify magnetic fields, while a more ambitious team from Harvard  targeted laser pulses at the worm’s neurons, and directed it to move in any directions they wanted,  even tricking the worm in thinking there’s food nearby.

robot lego

Worm ‘brain’ controls LEGO robot – what this means for the human brain

One of the most interesting projects in science today are the  BRAIN Initiative in the US and the Human Brain Project in Europe, which aim to map all the synapse connections in the human brain, or connectome, and ultimately simulate it. It’s an ambitious project with numerous challenges, but the possible benefits are well worth it. We could finally deconstruct neurodegenerative diseases like Parkinson’s or Alzheimer’s for instance, which would make finding a treatment and maybe even a cure a lot easier. The greatest insight however is a lot more philosophical: a potential definite answer to what is consciousness. It’s a question we’ve all asked one way or the other at least once in our lives, but deep down do we really want to know? I’m not sure, either. Anyway, when you’re undertaking a complex task such as mapping the human brain, you need to start simple. Analogously, you start with a worm’s brain.

A worm’s brain in a LEGO body

robot lego

The OpenWorm project is an online community project that wants to  reverse-engineer C elegans or the simple roundworm. We’ve written about the roundworm simply because it’s just a lab favorite for scientists, for obvious reasons. It breeds fast, so it’s great for studying genetics, it’s practically immortal so it’s great to test basically anything, and as far as neuroscience is concerned it has a tiny brain, which again makes it perfect. C elegans only has 302 neurons and 7,000 synapses, compared to 86 billion neurons and 100 trillion synapse found in a typical human brain. But creating algorithms to simulate the functions of even such a tiny winy brain is a huge task for the scientists and programmers from the UK, Ireland, Russia and the US. They’ve proved it can be done, though.

The first map of the synaptic connections, or connectome, of the brain of C. elegans in 1986 and a refined draft in 2006. Now, the OpenWorm team not only simulated the C. elegans brain, but also uploaded the simulation into lego robot that has all the equivalent limited body parts that the worm has – a sonar sensor that acts as a nose, and motors that replace its motor neurons on each side of its body. In the video below, you see what came out of it.

As you noticed, the robot moves forward or backward, and tripping the nose sensor grinds the robot to a halt. Ok, doesn’t seem impressive at first glance, but what sets it apart from your typical robot is that all these commands weren’t pre-programmed! The robot’s whole behavior is guided by algorithms that work with the worm’s connectome, labeling  sensory neurons, motor neurons, and interneurons which connect the two. For instance, stimulating the food sensor made the robot move forward.

Obviously, not all of the worm’s sensors were stimulated, nor simulated. The ultimate goal is to simulate the entire C. elegans brain, but for now this is truly a powerful demonstration of what can be obtained.

"Adaptive behavioral prioritization requires flexible outputs from fixed neural circuits. In C. elegans, the prioritization of feeding versus mate searching depends on biological sex (males will abandon food to search for mates, whereas hermaphrodites will not) as well as developmental stage and feeding status. Previously, we found that males are less attracted than hermaphrodites to the food-associated odorant diacetyl, suggesting that sensory modulation may contribute to behavioral prioritization," the researchers write in Current Biology. Image: Current Biology.

Males may be Wired to choose Sex over Food

Men are from Mars and women are from Venus, or so the old adage goes, but how different are men and women? I won’t go into debates like whether or not men and women are neurologically the same – it’s a far too exhaustive and exhausting subject for such a short article. Clearly, however, men and women are different in biological terms, and going beyond physical differences, there are numerous hormonal interactions that greatly vary between men and women. For instance, men may be wired to go to greater lengths than women to have sex, if we’re to judge from the findings of a recent study which found male roundworms would rather mate than gobble food.

Sex or food? It might not be a matter of opinion

"Adaptive behavioral prioritization requires flexible outputs from fixed neural circuits. In C. elegans, the prioritization of feeding versus mate searching depends on biological sex (males will abandon food to search for mates, whereas hermaphrodites will not) as well as developmental stage and feeding status. Previously, we found that males are less attracted than hermaphrodites to the food-associated odorant diacetyl, suggesting that sensory modulation may contribute to behavioral prioritization," the researchers write in Current Biology. Image: Current Biology.

“Adaptive behavioral prioritization requires flexible outputs from fixed neural circuits. In C. elegans, the prioritization of feeding versus mate searching depends on biological sex (males will abandon food to search for mates, whereas hermaphrodites will not) as well as developmental stage and feeding status. Previously, we found that males are less attracted than hermaphrodites to the food-associated odorant diacetyl, suggesting that sensory modulation may contribute to behavioral prioritization,” the researchers write in Current Biology. Image: Current Biology.

Both feeding and mating are deeply etched into our biology, being essential to survival and reproduction, so choosing between the two can be a tough judgement call. Simple, yet subtle changes to the brain circuitry can make this decision easier, according to the findings of a group of researchers at University of Rochester published in Current Biology.

“While we know that human behavior is influenced by numerous factors, including cultural and social norms, these findings point to basic biological mechanisms that may not only help explain some differences in behavior between males and females, but why different sexes may be more susceptible to certain neurological disorders,” lead author Douglas Portman said in a press release.

The researchers studied Caenorhabditis elegans, a type of microscopic roundworm and favorite lab pet for researchers studying anything from genetics, to diseases, to immortality. It’s important to note that there isn’t a clear distinction between males and females when C. elegans is concerned. The females are actually hermaphrodites, meaning they’re able to self-fertilize, but that doesn’t necessarily stop them from seeking mating partners in males, and as such are considered to be modified females.

The team focused on the roundworm’s sense of smell, which they used to probe their suspicions that male and females are wired differently. The Rochester researchers placed hermaphrodites in the center of a petri dish with some food, with an additional ring of tempting food surrounding them – an obstacle for the males placed at the edge of the dish. The males either had a normal genetic profile – the control group – or overexpressed the chemoreceptor ODR-10, related to the worms’ sense of smell and found to control their decision between food and sex.

The normal males made a B-line for the hermaphrodites at the center of the dish. The hermaphrodites produce ODR-10 receptors, making them more sensitive to food, which explains why they didn’t stray from their food, unlike the males. Given the choice between overexpressing ODR-10 and maintaining normal levels, males opted for the latter 10 to one, researchers say. The findings rang true to the researchers’ predictions – males prefer sex over food. At least male worms, but are we humans any different? This is definitely a lot harder to test, but the conclusions are nonetheless very interesting.

 

Scientists have grown mutated worms that don't get drunk. mage courtesy of Jon Pierce-Shimomura of The University of Texas at Austin.

Mutant worm that doesn’t get drunk could help end alcoholism

Scientists have grown mutated worms that don't get drunk. mage courtesy of Jon Pierce-Shimomura of The University of Texas at Austin.

Scientists have grown mutated worms that don’t get drunk. mage courtesy of Jon Pierce-Shimomura of The University of Texas at Austin.

An unlikely worm might help millions of people fighting alcohol addiction. No, you won’t find it in tequila, but in the labs of neuroscientists at University of Texas at Austin who have engineered  Caenorhabditis elegans – one of the most popular animal models in science – to become insensitive to alcohol intoxication. The findings, if replicated on mice and then humans in clinical trials via a drug, could help devise treatments for  people going through alcohol withdrawal. 

The researchers achieved this feat by inserting a modified human alcohol target – any neuronal molecule that binds alcohol. The target in question was a neuronal channel called the BK channel, regulates many important functions including activity of neurons, blood vessels, the respiratory tract and bladder. However, the mutation only causes alcohol insensitivity and preserves all the other vital functions.

“This is the first example of altering a human alcohol target to prevent intoxication in an animal,” says corresponding author, Jon Pierce-Shimomura, assistant professor in the university’s College of Natural Sciences and Waggoner Center for Alcohol and Addiction Research.

“We got pretty lucky and found a way to make the channel insensitive to alcohol without affecting its normal function,” says Pierce-Shimomura.

To find this target, Pierce-Shimomura and his team proceeded largely by trial-and-error.  Eventually, they stumbled upon a genetic modification of the channel that stopped it from activating in the presence of ethanol.

“We tried a brute force approach, testing hundreds of mutations to empirically determine which one would allow the BK channel to function normally [while still] preventing alcohol from activating it.”

[RELATED] A gene mutation linked to alcohol abuse found

Now you can’t get drunk. Is that a good thing?

How does a drunk worm look like in the first place? Well, when C. elegans has more than it can handle, it slows its crawling and moves less from side to side. The worm also stops laying eggs, which builds up in their bodies and thus proved to be a great marker to assess whether or not the mutation worked. Even so, alcohol is a very tricky chemical. Unlike other drugs like cocaine that works its magic on specific regions of the brain, alcohol seems to be all over the place, targeting many regions of the brain with various effects on the body. As such, various other aspects of alcohol addiction, such as tolerance, craving and the symptoms of withdrawal, may be influenced by different alcohol targets.

[NOW READ] Origin of alcohol consumption traced back 10 millions years ago

Will we get to see a drug in the future the kind James Bond uses to drink his enemies under the table soon? Maybe, maybe not. The researchers first need to investigate the findings further by replicating the experiment in mice, which are far more complex organisms than worms. If such a drug worked on humans too, and with manageable side effects (mutated alcohol targets might cause some serious backfiring considering they’re involved in other important bodily functions), then it could become a serious tool for curving alcohol addiction.

“Our findings provide exciting evidence that future pharmaceuticals might aim at this portion of the alcohol target to prevent problems in alcohol abuse disorders,” says Pierce-Shimomura. “However, it remains to be seen which aspects of these disorders would benefit.”

The findings were reported in The Journal of Neuroscience.

Strict diet doubles lifespan of worms

Taking food away from C. elegans in larval stages suspends their development; while they still wiggle around and look for food, they are in a state of arrested development. However, when food becomes plentiful again, they start to develop normally – but live twice as long.

This shows the nematode worm C. elegans with muscle cells fluorescently labeled in green and germ cells fluorescently labeled in red. These cells and others pause at a checkpoint in development and slow their aging when worms encounter a period of starvation. Credit: David Sherwood Lab, Duke University

This remarkably simple way of achieving longevity is not entirely surprising. It has been known for quite a while that a low intake of nutrients and reduced cellular activity are generally linked with longevity – but doubling the lifespan only through a strict but temporary diet, that’s something quite surprising.

“It is possible that low-nutrient diets set off the same pathways in us to put our cells in a quiescent state,” said David R. Sherwood, an associate professor of biology at Duke University. “The trick is to find a way to pharmacologically manipulate this process so that we can get the anti-aging benefits without the pain of diet restriction.”

Sherwood and his colleagues from Duke University took a myriad of creatures and deprived them of food, in order to study the effects on longevity. They studied rats, mice, yeast, flies, spiders, fish, monkeys and worms; the effects on longevity varied between 30 percent to 200 percent, but in all cases, the lifespan was increased. Caenorhabditis elegans, a non-parasitic worm showed the most promise.

In nature, C. elegans often suffers from hunger, and its bodily development heavily depends on the available nutrients. But what researchers observed was that during the later stages of the larval development (known as L3 and L4), if they don’t have enough nutrients, they just stop developing. It’s as if they simply pause or slow down their development until they have sufficient nutrients around.

“Development isn’t a continuous nonstop process,” said Schindler, who is lead author of the study. “Organisms have to monitor their environment and decide whether or not it is amenable to their development. If it isn’t, they stop, if it is, they go. Those checkpoints seem to exist to allow the animal to make that decision. And the decision has implications, because the resources either go to development or to survival.”

Researchers starved the larvae for two weeks, and then fed them nutrients they would stumble upon in nature. What they observed was that the worms would develop normally after that – with their lifespans drastically increased.

“This study has implications not only for aging, but also for cancer,” said Sherwood. “One of the biggest mysteries in cancer is how cancer cells metastasize early and then lie dormant for years before reawakening. My guess is that the pathways in worms that are arresting these cells and waking them up again are going to be the same pathways that are in human cancer metastases.”

 

Journal Reference: Adam J. Schindler, L. Ryan Baugh, David R. Sherwood. Identification of Late Larval Stage Developmental Checkpoints in Caenorhabditis elegans Regulated by Insulin/IGF and Steroid Hormone Signaling Pathways. PLoS Genetics, 2014; 10 (6): e1004426 DOI: 10.1371/journal.pgen.1004426

Caenorhabditis elegans (C. elegans) is a small (about 1 mm long as an adult), free living nematode (round worm). Simple as it is, it can be regarded as a prototype to study biological locomotion in various fluid environment.

Of mind control: scientists manipulate worm and take control of its behavior

In a remarkable feat of science, scientists at Harvard University have surpassed seemingly insurmountable technological challenges have managed to take over the behavior of a lab worm. Using precisely targeted laser pulses at the worm’s neurons, scientists were able to direct it to move in any directions they wanted, and even trick it in thinking there’s food nearby. These fantastic results provide an important milestone in the quest to understand how sensory information is transmitted into behavior.

Caenorhabditis elegans (C. elegans) is a small (about 1 mm long as an adult), free living nematode (round worm). Simple as it is, it can be regarded as a prototype to study biological locomotion in various fluid environment.

Caenorhabditis elegans (C. elegans) is a small (about 1 mm long as an adult), free living nematode (round worm). Simple as it is, it can be regarded as a prototype to study biological locomotion in various fluid environment.

The researchers used the favored lab testing specimen, the common Caenorhabditis elegans (C. elegans) worm, to test their theories, which they genetically altered in order for its neurons to give off fluorescent light, allowing them to be tracked during experiments. Also, genes in the worm were altered to make its neurons sensitive to light, so they could be stimulated with pulses of light – this is optogenetics.

“If we can understand simple nervous systems to the point of completely controlling them, then it may be a possibility that we can gain a comprehensive understanding of more complex systems,” said team leader Sharad Ramanathan, an Assistant Professor of Molecular and Cellular Biology and of Applied Physics. “This gives us a framework to think about neural circuits, how to manipulate them, which circuit to manipulate and what activity patterns to produce in them.

“Extremely important work in the literature has focused on ablating neurons, or studying mutants that affect neuronal function and mapping out the connectivity of the entire nervous system. ” he added.

“Most of these approaches have discovered neurons necessary for specific behavior by destroying them. The question we were trying to answer was: Instead of breaking the system to understand it, can we essentially hijack the key neurons that are sufficient to control behavior and use these neurons to force the animal to do what we want?”

Taking over a worm’s brain

Targeting the worm’s neurons with laser pulses, however proved to be an incredible challenge. The researchers manage to overcome the difficulties they faced though, like developing a movable table which keeps the worm centered to the laser beam no matter how fast or in what direction it might move, and implementing a custom-built computer hardware and software to insure the laser pulses fire at the required split-second speeds – once every 20 milliseconds, or about 50 times a second.

“The goal is to activate only one neuron,” Ramanathan said. “That’s challenging because the animal is moving, and the neurons are densely packed near its head, so the challenge is to acquire an image of the animal, process that image, identify the neuron, track the animal, position your laser and shoot the particularly neuron”

They discovered that controlling the dynamics of activity in just one interneuron pair (AIY) was sufficient to force the animal to locate, turn towards, and track virtual light gradient. What was mind blowing, for me to learn at least, was that the scientists didn’t only manipulate the worm’s behavior, but its senses also. They proved this by tricking the worm’s brain into believing food was nearby, causing it to make a beeline toward the imaginary meal.

“By manipulating the neural system of this animal, we can make it turn left, we can make it turn right, we can make it go in a loop, we can make it think there is food nearby,” Ramanathan said. “We want to understand the brain of this animal, which has only a few hundred neurons, completely and essentially turn it into a video game, where we can control all of its behaviors.”

Before you form any modern Manchurian candidate paranoia influenced ideas, consider that C. elegans has one of the most primitive brains, as far as complex organisms are concerned – boosting a disappointing 302 neurons. It’s impossible for a similar set-up to render similar results for a snake, let alone a human. Still, the Harvard researchers intend of improving their system and test on more complex organisms.

Findings were published in the journal Nature.

The Caenorhabditis elegans or C. elegans common ground worm.

Worms show that Mars colonization is possible

There are numerous challenges that come with outer Earth colonization of distant planets like Mars, or our neighboring moon, and one of the major issues scientists have addressed is reproduction. Part of a  recently published study, scientists have tracked the development of worm cultures in space in an experiment designed to study how micro-gravity and radiation has affected them.

Back in 2006, researchers blasted off to the ISS 4,000 specimens of Caenorhabditis elegans (C elegans), a soil-living worm used extensively in various researchers through out the years. Until recently, 12 generation of the nematode have been successfully bred, passing from egg to adulthood, which reproduced very much in the same way like on Earth.

The Caenorhabditis elegans  or C. elegans common ground worm.

The Caenorhabditis elegans or C. elegans common ground worm.

Remarkably enough, C elegans is very much similar to humans. Alright, let me explain. It has 20,000 protein-coding genes, more or less the same amount as humans, which also roughly possess the same functions as ours. Two thousand of these genes have a role in promoting muscle function and 50 to 60 per cent of these have very obvious human counterparts. In 1998, the creature commonly found in the soil of your backyard was the first multi-celullar being to have its genome completely sequenced.

“We have been able to show that worms can grow and reproduce in space for long enough to reach another planet, and that we can remotely monitor their health,” study lead author Nathaniel Szewczyk, of the University of Nottingham in the United Kingdom, said in a statement.

“As a result, C. elegans is a cost-effective option for discovering and studying the biological effects of deep space missions,” Szewczyk added. “Ultimately, we are now in a position to be able to remotely grow and study an animal on another planet.”

The worms were bred using a compact automated culturing system that can be monitored remotely, which transferred a subset of worms to fresh food every month, filming the worms’ progress as they went. Since the results were monitored in real time directly from Earth, it spared scientists the nerves which would’ve been tensed to oblivion resulting from data solely dependent on a sample re-entry.

The researchers conclude that C. elegans shows that man could survive as an interplaneteray species, and provides invaluable data for further research regarding radiation exposure and muscle atrofiation, the most pressing issues at hand as far as manned space exploration is concerned.

“While it may seem surprising, many of the biological changes that happen during spaceflight affect astronauts and worms, and in the same way,” Szewczyk said.

C. elegans has gone farther away than any worm on Earth, and its journey is far from over. Considering the success of this study, the researchers are considering sending a batch as far as on to the Mars surface. This would provide genuine readings of just how dangerous the high radiation levels found in deep space, and on the Red Planet’s surface, are to animal life. We’re still waiting for some results from the cephalopods  study on the ISS, where baby squids were brought into space for experiments.

“Worms allow us to detect changes in growth, development, reproduction and behavior in response to environmental conditions such as toxins or in response to deep space missions,” Szewczyk said. “Given the high failure rate of Mars missions, use of worms allows us to safely and relatively cheaply test spacecraft systems prior to manned missions.”

The researchers’ results were published in a recent edition of the Royal Society journal.

image credit

Aging, a simple error of evolution??

 

aging

Everybody pondered at least once in their lives the possibility of being immortal, and this idea sparkled in the immagination of many people throughout history. Now, Stuart Kim, a PhD at Stanford and professor of developmental biology and genetics conducted a study that led to results that shocked pretty much everybody involved, contradicting the currently accepted theory that aging is represented by a damaging of the tissue, similar in many reasons to the rust of a circuit.

The study led to the conclusion the instead aging is driven by a genetic instruction, coded deep into the genome; this of course leads to the conclusion that (if this is true) it could someday be possible to turn off the gene responsable for the process, which seems really unbelievable. Still, that is what the study conducted on C. elegans showed.

By comparing the old worms to the younger worms, the team of scientists discovered age-related shifts in levels of three transcription factors, which are (very lightly explained) the marks of turning genes on and off. The other, older, and (until now) wider accepted theory is that aging is a tear and wear process; the body acumulates toxins, radiations, which cause an irreversible process. But Stanford researchers published findings which tell a different story.

“Our data just didn’t fit the current model of damage accumulation, and so we had to consider the alternative model of developmental drift,” Kim said.

Basically what they did is used a trigger to find out if there were any changes in gene expression and found hundreds of age-regulated genes switched on and off by a single transcription factor which is more abundent by age. So it looked as though worm aging wasn’t a storm of chemical damage. It seems we’ll have a bit of waiting to do until more research is done in this directions, but the results could be very impressive.

Bloodless Worm Sheds Light on Human Blood

c. elegans

University of Maryland researchers have managed to shed some light in an important matter which puzzled medical scientists and not only for ages: how iron carried in human blood is absorbed and transported into the body. Among the benefits of this discovery I’ll just name a better understanding of iron deficiency, the world’s number one nutritional disorder; a better understanding leads to a better treatment.With C. elegans , a common microscopic worm that lives in dirt, Iqbal Hamza, assistant professor of animal and avian sciences and his team have positively identified previously unknown proteins that play a vital part in transporting heme, the molecule that creates hemoglobin in blood and carries iron. It’s an important step in understanding how our bodies process iron and exactly how the blood plays its role in transportation and processing.

“The structure of hemoglobin has been crystallized over and over,” says Hamza, “but no one knows how the heme gets into the globin, or how humans absorb iron, which is mostly in the form of heme. To understand the underlying issues of nutritional and genetic causes of iron deficiency, we are looking at the molecules and mechanisms involved in heme absorption. Once you understand transport of heme, you can more effectively deliver it to better absorb iron in the human intestine.”

The study revealed several findings that could lead to new treatment for iron deficiency. One was the discovery that genes are involved in heme transport. C. elegans can also be studied for finding out other things, but for this it was necessary, because due to the fact that it has only one valve that controls the heme transport, scientists knew exactly where heme was entering the worm’s intestine, where, as in humans, it is absorbed.