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Rabies Virus
This negative-stained TEM shows rabies virions (at 70,000x magnification) purified from an infected cell culture.
In Rabid: A Cultural History of the World’s Most Diabolical Virus, Wired senior editor Bill Wasik and veterinarian Monica Murphy recount the fascinating history of the ubiquitous and menacing rabies virus, writing:
It is the most fatal virus in the world, a pathogen that kills nearly 100 percent of its hosts in most species, including humans. Fittingly, the rabies virus is shaped like a bullet: a cylindrical shell of glycoproteins and lipids that carries, in its rounded tip, a malevolent payload of helical RNA. On entering a living thing, it eschews the bloodstream, the default route of nearly all viruses but a path heavily guarded by immuno-protective sentries. Instead, like almost no other virus known to science, rabies sets its course through the nervous system, creeping upstream at one or two centimeters per day (on average) through the axoplasm, the transmission lines that conduct electrical impulses to and from the brain. Once inside the brain, the virus works slowly, diligently, fatally to warp the mind, suppressing the rational and stimulating the animal. Aggression rises to fever pitch; inhibitions melt away; salivation increases. The infected creature now has only days to live, and these he will likely spend on the attack, foaming at the mouth, chasing and lunging and biting in the throes of madness — because the demon that possesses him seeks more hosts.
If it sounds like a horror movie, we should not be surprised, for it is a scenario bound up into our very concept of horror. Rabies is a scourge as old as human civilization, and the terror of its manifestation is a fundamental human fear, because it challenges the boundary of humanity itself. That is, it troubles the line where man ends and animal begins.
In spite of Louis Pasteur’s success in pioneering the rabies vaccine (more than two centuries ago), 55,000 people still die from rabies globally each year — that’s one death from rabies every ten minutes.
Content Credit: via Maria Popova at Brain Pickings.
Photo Credit: Frederick Murphy at the University of Texas Medical Branch, Galveston, Texas.
The Creation Museum - An Analysis
At Quantumaniac, I would never openly discriminate against anyone for holding a particular religious belief, as I understand that such beliefs can be very personal for some people. However, occasionally I stumble across something so egregious that it must be brought up - harboring beliefs is one thing, but spreading fallacies in this way is outrageous. I know that I’m going to get tons of hate mail for this post, but nonetheless - enter the Creation Museum.
The Creation “Museum” is an institution in Kentucky, USA, opened by Ken Ham, that aims to “present an account of the origins of the universe, life, mankind, and man’s early history according to a literal, young earth creationist perspective of the Book of Genesis in the bible.” Here are just a few of the “scientific facts” presented at the museum:
- the Earth and all of its life forms were created 6,000 years ago over a six-day period
- humans and dinosaurs once coexisted, and that dinosaurs were on Noah’s Ark.
- the reason there are different races is because of birth defects which caused early black people’s skin to discolor.
- the waters of Noah’s flood carved out the Grand Canyon in a matter of days.
- there are no fundamental physical laws of the universe, everything is subject to disruption and miracle.
- that all logic is irrelevant, and to never trust “man’s word,” only “God’s word.” They go as far as to tell children that what they may be learning in schools about science is wrong.
- there are guards present to suppress criticism and nonbelievers (you must sign a document upon entering that requires you not to discuss any contrary ideas!).
The most disconcerting fact about this establishment is that all of its claims are presented as tested and legitimate scientific theories. This is inexcusable. It is one thing for a person to be a “young-Earth creationist,” but they are already lost to science and reason, they’re not who I’m concerned about.I pity the children. Hundreds of thousands of young, impressionable children visit this museum every year, and have these ideas thrust upon them as irrefutable facts. The ideas presented in this “museum” are flagrant lies that stomp on the legitimacies of science, shutting the door on disciplines such as biology, physics, cosmology, chemistry, and reason. Presenting these as simply religious beliefs is fine and a perfectly acceptable, and you will hear no argument from me - but everything in this museum is presented as facts. Scientific, proven, facts. In a country where only about 28% of the population is “scientifically literate,” establishments like this are a legitimate problem that must be addressed.If you’d like to learn more about the museum, here are features by various other sites:Let the hate mail begin.I’m friends with many fellow science-lovers who have no idea this is a problem. It’s about time they knew.
It always gets me incredibly miffed that I live in the same state as The Creation Museum. This is an issue. At least it’s not publicly funded (as far as I know).
People who age prematurely could soon benefit from rejuvenation therapies
Humans age at different rates, as a result of various factors like lifestyle and genetics. Now, a new study from the ENGAGE Consortium suggests that people who age faster are at an increased risk of developing age-related diseases like heart disease, multiple sclerosis, and various cancers. The researchers suggest that the way we age is affected by changes to a part of your chromosomes called a telomere. And it’s possible that tinkering with telomeres could lead to rejuvenation therapies.
Biologists have known for some time that aging can be linked to our cellular expiry dates; our cells can only replicate so many times before they start to degrade, the result of increasingly shortening telomere lengths in chromosomes — strands of DNA that are stored in the nucleus of cells.
We’re all born with different telomere lengths, and they get shorter at different rates. Biologists measure this as our rate of ‘biological aging’ as opposed to our chronological age; some 90-year-olds have the same ‘biological age’ as, say, some 80-year-olds.
Hoping to investigate this further, a international team of scientists took to the task of measuring the telomere lengths of 37,684 individuals to see if they could identify the genetic variants responsible for telomere length — and whether those variants could be tied to the risk of various diseases.
No doubt, this was a major study, lasting five years and involving 14 centers across eight countries. It’s part of the ENGAGE Consortium (European Network for Genetic and Genomic Epidemiology), a research project aiming to translate the copious amounts of genetic data that’s pouring into meaningful clinical applications.
The scientists were able to identify no less than seven genetic variants that affect telomere length and were directly associated with specific diseases. Specifically, they linked the variants to several types of cancer, including colorectal cancer. They also connected them to multiple sclerosis, celiac disease — and an increased risk for heart attacks.
To better understand this connection, I spoke to Dr. Preston Estep, the Chief Scientific Officer of TeloMe, Inc., and an expert on genetics and human aging. Specifically, I asked him what biological mechanism could account for the shortening of the telomeres.
“Cell replication shortens telomeres, and telomerase, an enzyme encoded in our genes, makes telomeres longer,” he said. “The overall balance of these two determines length, and typically telomerase levels are low enough to allow gradual shortening with time.”
He says that people vary a lot in both starting telomere length and rate of shortening.
“One very important discovery made by the ENGAGE consortium is that genetic variants that predispose to shorter telomeres and higher disease risk are extremely common,” he told io9. “I’m sure many people are surprised that common and even predominant genetic variants predispose to higher risk of disease and mortality, but we are finding this more often as more high-quality and large-scale studies like the ENGAGE study are published. However, from an evolutionary perspective this is to be expected, since the negative effects of these variants don’t occur until later in the post-reproductive phase of life.”
As Estep noted, the telomerase enzyme makes our telomeres longer. This insight, along with the genetic findings of ENGAGE, could mean that rejuvenation therapies might soon be possible. I asked Estep how difficult it is to measure someone’s telomere length and whether or not a clinical application awaits us in the future.
“From our perspective, it is technically easy to measure average telomere length, and more difficult to do a detailed analysis that provides a detailed look at the distribution of telomere lengths from shortest to longest,” he said.
The problem, however, is getting access to testing since all tests to date have been fairly expensive and done on blood.
“Over the past 2-plus years we have developed and refined methods for measuring telomeres in saliva, and for establishing a mail-based saliva collection and processing pipeline,” he said. “That allows us to keep costs low and make telomere testing available to essentially everyone.”
But eventually, says Estep, the testing of telomeres will be very similar to routine cholesterol or blood pressure testing in a number of important ways:
- Dynamic: Telomere lengths change over time and are influenced by both genetics and many lifestyle factors
- Meaningful: Very short or very long telomeres not only are associated with higher risk for disease and mortality, they are a cause
- Treatable: Telomere length can be controlled not only through lifestyle factors, but also through therapeutic means
And in fact, Estep is so serious about this that his company has set up an Indiegogo campaign for introducing people to telomere testing.
In terms of actual approaches, he has some ideas.
“Some weak ones that are already in use are vigorous exercise, stress reduction, good diet — the standard list of positive lifestyle factors,” he told us. “However, people don’t respond equally, and those who have very short telomeres might consider more potent means.”
He says that telomerase activator supplements are already being sold, but that people should approach this whole area with great caution.
“I also think that more studies are needed to better understand the benefits and risks,” he added.
“Nevertheless, people with very short telomeres are living with higher risk for many serious health issues, and their best hope for reducing the risk is to fix the problem,” he said. “That isn’t a recommendation, it is simply a statement of fact.”
As for the ENGAGE researchers themselves, they’re also hopeful.
“The findings open of the possibility that manipulating telomere length could have health benefits,” noted Dr. Veryan Codd through a statement. “While there is a long way to go before any clinical application, there are data in experimental models where lengthening telomere length has been shown to retard and in some situations reverse age-related changes in several organs.”
Images: Creations/Shutterstock; HudsonAlpha;
Sorting out the structure of a Parkinson’s protein
Computer modeling may resolve conflicting results and offer hints for new drug-design strategies.
Clumps of proteins that accumulate in brain cells are a hallmark of neurological diseases such as dementia, Parkinson’s disease and Alzheimer’s disease. Over the past several years, there has been much controversy over the structure of one of those proteins, known as alpha synuclein.
MIT computational scientists have now modeled the structure of that protein, most commonly associated with Parkinson’s, and found that it can take on either of two proposed states — floppy or rigid. The findings suggest that forcing the protein to switch to the rigid structure, which does not aggregate, could offer a new way to treat Parkinson’s, says Collin Stultz, an associate professor of electrical engineering and computer science at MIT.
“If alpha synuclein can really adopt this ordered structure that does not aggregate, you could imagine a drug-design strategy that stabilizes these ordered structures to prevent them from aggregating,” says Stultz, who is the senior author of a paper describing the findings in a recent issue of the Journal of the American Chemical Society.
For decades, scientists have believed that alpha synuclein, which forms clumps known as Lewy bodies in brain cells and other neurons, is inherently disordered and floppy. However, in 2011 Harvard University neurologist Dennis Selkoe and colleagues reported that after carefully extracting alpha synuclein from cells, they found it to have a very well-defined, folded structure.
That surprising finding set off a scientific controversy. Some tried and failed to replicate the finding, but scientists at Brandeis University, led by Thomas Pochapsky and Gregory Petsko, also found folded (or ordered) structures in the alpha synuclein protein.
Stultz and his group decided to jump into the fray, working with Pochapsky’s lab, and developed a computer-modeling approach to predict what kind of structures the protein might take. Working with the structural data obtained by the Brandeis researchers, Stultz created a model that calculates the probabilities of many different possible structures, to determine what set of structures would best explain the experimental data.
The calculations suggest that the protein can rapidly switch among many different conformations. At any given time, about 70 percent of individual proteins will be in one of the many possible disordered states, which exist as single molecules of the alpha synuclein protein. When three or four of the proteins join together, they can assume a mix of possible rigid structures, including helices and beta strands (protein chains that can link together to form sheets).
“On the one hand, the people who say it’s disordered are right, because a majority of the protein is disordered,” Stultz says. “And the people who would say that it’s ordered are not wrong; it’s just a very small fraction of the protein that is ordered.”
The MIT researchers also found that when alpha synuclein adopts an ordered structure, similar to that described by Selkoe and co-workers, the portions of the protein that tend to aggregate with other molecules are buried deep within the structure, explaining why those ordered forms do not clump together.
Stultz is now working to figure out what controls the protein’s configuration. There is some evidence that other molecules in the cell can modify alpha synuclein, forcing it to assume one conformation or another.
“If this structure really does exist, we have a new way now of potentially designing drugs that will prevent aggregation of alpha synuclein,” he says.
Identification First Potentially Effective Therapy for Human Prion Disease
Human diseases caused by misfolded proteins known as prions are some of most rare yet terrifying on the planet—incurable with disturbing symptoms that include dementia, personality shifts, hallucinations and coordination problems. The most well-known of these is Creutzfeldt-Jakob disease, which can be described as the naturally occurring human equivalent of mad cow disease.
Now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have for the first time identified a pair of drugs already approved for human use that show anti-prion activity and, for one of them, great promise in treating these universally fatal disorders.
The study, led by TSRI Professor Corinne Lasmézas and performed in collaboration with TSRI Professor Emeritus Charles Weissmann and Director of Lead Identification Peter Hodder, was published this week online ahead of print by the journal Proceedings of the National Academy of Sciences.
The new study used an innovative high-throughput screening technique to uncover compounds that decrease the amount of the normal form of the prion protein (PrP, which becomes distorted by the disease) at the cell surface. The scientists found two compounds that reduced PrP on cell surfaces by approximately 70 percent in the screening and follow up tests.
The two compounds are already marketed as the drugs tacrolimus and astemizole.
Tacrolimus is an immune suppressant widely used in organ transplantation. Tacrolimus could prove problematic as an anti-prion drug, however, because of issues including possible neurotoxicity.
However, astemizole is an antihistamine that has potential for use as an anti-prion drug. While withdrawn voluntarily from the U.S. over-the-counter market in 1999 because of rare cardiac arrhythmias when used in high doses, it has been available in generic form in more than 30 countries and has a well-established safety profile. Astemizole not only crosses the blood-brain barrier, but works effectively at a relatively low concentration.
Lasmézas noted that astemizole appears to stimulate autophagy, the process by which cells eliminate unwanted components. “Autophagy is involved in several protein misfolding neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases,” she said. “So future studies on the mode of action of astemizole may uncover potentially new therapeutic targets for prion diseases and similar disorders.”
The study noted that eliminating cell surface PrP expression could also be a potentially new approach to treat Alzheimer’s disease, which is characterized by the build-up of amyloid β plaque in the brain. PrP is a cell surface receptor for Aβ peptides and helps mediate a number of critical deleterious processes in animal models of the disease.
Scanning electron micrographs of diatoms, microscopic algae that form the base of the food chain and produce 20% of Earth’s oxygen.
The beautiful base of the pyramid of biology, feeding our air, land and life.
9 Year Old Discovers New Dinosaur And Has It Named After Her
One little girl’s odd hobby has led to an extraordinary find for British paleontologists.
At the age of 9, Daisy Morris has discovered a new dinosaur species, which scientists have since named after her. The new creature has been dubbed Vectidraco daisymorrisae, the “Dragon from the Isle of Wight.”
Daisy was just 4 when she stumbled upon the fossilized remains of an unknown animal during a family walk on the beach in 2009. The family lives near the coast of England’s Isle of Wight — also known as the “dinosaur capital of Great Britain.”
“She has a very good eye for tiny little fossils,” her mother Sian Morris told BBC. Daisy apparently first began fossil hunting at age 3. “She found these tiny little black bones sticking out of the mud and decided to dig a bit further and scoop them all out,” her mother said.
Realizing that Daisy had possibly uncovered an ancient specimen, her family took the findings to Southampton University’s fossil expert Martin Simpson.
Over the past several years, the bones Daisy discovered have been thoroughly analyzed by paleontologists. The findings were finally published this Monday. The fossilized remains belong to a previously unknown genus and species of a small flying reptile called the pterosaur.
The remains date back to the Lower Cretaceous period and may be up to 115 million years old.
The family has donated the fossils to the Natural History Museum while Daisy’s personal collection continues to grow. Sian Morris told the Daily Mail, “She’s fascinated and we’re very proud of her.”
Source: The Huffington Post
The Oldest Star in the Universe
Hank tells the story of the mysterious star known as “Methuseleh,” and why scientists think that it is the oldest known star in the universe.
References
Watch Galaxies Collide: http://commons.wikimedia.org/w/index.php?title=File%3AAndromeda_and_Milky_Way_collision.ogg
Strange ‘Methuselah’ Star Looks Older Than the Universe: http://www.space.com/20112-oldest-known-star-universe.html
Hubble Finds Birth Certificate of Oldest Known Star: http://www.nasa.gov/mission_pages/hubble/science/hd140283.html
In theory, there are lots of advantages to ditching males altogether. There is no need to waste time looking for a mate, for instance, or risking catching STDs. Yet despite this, surprisingly few animals have dispensed with males. The common checkered whiptail lizard,Aspidoscelis tesselata, is one of them, along with a few other species of whiptails and some geckos. These animals do sometimes still show signs of mating behaviour, such as engaging in “pseudocopulation” with other females.
Read about the other five fatherless animals here
Variola virus (smallpox)
Smallpox is considered to be a disease of antiquity, but was once the scourge of all mankind. It is a member of the poxviridae family, has a double stranded DNA and is ellipsoid-shaped with an outer envelope. The virus only infects humans and has one stable serotype.
It’s Okay to be Smart - Why is the Sky Any Color?
Why is the sky blue? It’s a question that you’d think kids have been asking for thousands of years, but it might not be that old at all. The ancient Greek poet Homer never used a word for blue in The Odyssey or The Iliad, because blue is one of the last colors that cultures pick out a word for.
In this episode, I’ll tell you not only why the sky is blue, but why it’s red at sunset. It turns out, those colors are all part of the same sunbeam. And when you’re looking at a blue sky, you could be sharing a special moment with someone thousands of miles away. Next time a kid (or the kid inside you) wants to know why the sky is blue, you’ll have science to back you up!
(We know that the Earth turns the wrong direction in the animation, sorry about that. Something weird happened when we were programming the animation and it got reversed. Or maybe time travel!)
References for this episode: http://dft.ba/-4Wus
Joe’s Youtube series is turning out to be pretty informative!
Artificial jellyfish built from rat cells
Reverse-engineered life form could be used to test drugs.
A jellyfish made of silicone and rat heart cells ‘swims’ in water when subjected to an electric field. Image: Harvard University/Caltech
Bioengineers have made an artificial jellyfish using silicone and muscle cells from a rat’s heart. The synthetic creature, dubbed a medusoid, looks like a flower with eight petals. When placed in an electric field, it pulses and swims exactly like its living counterpart.
“Morphologically, we’ve built a jellyfish. Functionally, we’ve built a jellyfish. Genetically, this thing is a rat,” says Kit Parker, a biophysicist at Harvard University in Cambridge, Massachusetts, who led the work. The project is described today in Nature Biotechnology.
Parker’s lab works on creating artificial models of human heart tissues for regenerating organs and testing drugs, and the team built the medusoid as a way of understanding the “fundamental laws of muscular pumps”. It is an engineer’s approach to basic science: prove that you have identified the right principles by building something with them.
In 2007, Parker was searching for new ways of studying muscular pumps when he visited the New England Aquarium in Boston, Massachusetts. “I saw the jellyfish display and it hit me like a thunderbolt,” he says. “I thought: I know I can build that.” To do so, he recruited John Dabiri, a bioengineer who studies biological propulsion at the California Institute of Technology (Caltech) in Pasadena. “I grabbed him and said, ‘John, I think I can build a jellyfish.’ He didn’t know who I was, but I was pretty excited and waving my arms, and I think he was afraid to say no.”
Janna Nawroth, a graduate student at Caltech who performed most of the experiments, began by mapping every cell in the bodies of juvenile moon jellies (Aurelia aurita) to understand how they swim. A moon jelly’s bell consists of a single layer of muscle, with fibres that are tightly aligned around a central ring and along eight spokes.
To make the bell beat downwards, electrical signals spread through the muscle in a smooth wave, “like when you drop a pebble in water”, says Parker. “It’s exactly like what you see in the heart. My bet is that to get a muscular pump, the electrical activity has got to spread as a wavefront.”
Further information:
Gladstone scientists discover that DNA damage occurs as part of normal brain activity
Findings provide additional support for strategies to fight Alzheimer’s disease
Scientists at the Gladstone Institutes have discovered that a certain type of DNA damage long thought to be particularly detrimental to brain cells can actually be part of a regular, non-harmful process. The team further found that disruptions to this process occur in mouse models of Alzheimer’s disease—and identified two therapeutic strategies that reduce these disruptions.
Scientists have long known that DNA damage occurs in every cell, accumulating as we age. But a particular type of DNA damage, known as a double-strand break, or DSB, has long been considered a major force behind age-related illnesses such as Alzheimer’s. Today, researchers in the laboratory of Gladstone Senior Investigator Lennart Mucke, MD, report in Nature Neuroscience that DSBs in neuronal cells in the brain can also be part of normal brain functions such as learning—as long as the DSBs are tightly controlled and repaired in good time. Further, the accumulation of the amyloid-beta protein in the brain—widely thought to be a major cause of Alzheimer’s disease—increases the number of neurons with DSBs and delays their repair.
“It is both novel and intriguing team’s finding that the accumulation and repair of DSBs may be part of normal learning,” said Fred H. Gage, PhD, of the Salk Institute who was not involved in this study. “Their discovery that the Alzheimer’s-like mice exhibited higher baseline DSBs, which weren’t repaired, increases these findings’ relevance and provides new understanding of this deadly disease’s underlying mechanisms.”
In laboratory experiments, two groups of mice explored a new environment filled with unfamiliar sights, smells and textures. One group was genetically modified to simulate key aspects of Alzheimer’s, and the other was a healthy, control group. As the mice explored, their neurons became stimulated as they processed new information. After two hours, the mice were returned to their familiar, home environment.
The investigators then examined the neurons of the mice for markers of DSBs. The control group showed an increase in DSBs right after they explored the new environment—but after being returned to their home environment, DSB levels dropped.
“We were initially surprised to find neuronal DSBs in the brains of healthy mice,” said Elsa Suberbielle, DVM, PhD, Gladstone postdoctoral fellow and the paper’s lead author. “But the close link between neuronal stimulation and DSBs, and the finding that these DSBs were repaired after the mice returned to their home environment, suggest that DSBs are an integral part of normal brain activity. We think that this damage-and-repair pattern might help the animals learn by facilitating rapid changes in the conversion of neuronal DNA into proteins that are involved in forming memories.”
The group of mice modified to simulate Alzheimer’s had higher DSB levels at the start—levels that rose even higher during neuronal stimulation. In addition, the team noticed a substantial delay in the DNA-repair process.
To counteract the accumulation of DSBs, the team first used a therapeutic approach built on two recent studies—one of which was led by Dr. Mucke and his team—that showed the widely used anti-epileptic drug levetiracetam could improve neuronal communication and memory in both mouse models of Alzheimer’s and in humans in the disease’s earliest stages. The mice they treated with the FDA-approved drug had fewer DSBs. In their second strategy, they genetically modified mice to lack the brain protein called tau—another protein implicated in Alzheimer’s. This manipulation, which they had previously found to prevent abnormal brain activity, also prevented the excessive accumulation of DSBs.
The team’s findings suggest that restoring proper neuronal communication is important for staving off the effects of Alzheimer’s—perhaps by maintaining the delicate balance between DNA damage and repair.
“Currently, we have no effective treatments to slow, prevent or halt Alzheimer’s, from which more than 5 million people suffer in the United States alone,” said Dr. Mucke, who directs neurological research at Gladstone and is a professor of neuroscience and neurology at the University of California, San Francisco, with which Gladstone is affiliated. “The need to decipher the causes of Alzheimer’s and to find better therapeutic solutions has never been more important—or urgent. Our results suggest that readily available drugs could help protect neurons against some of the damages inflicted by this illness. In the future, we will further explore these therapeutic strategies. We also hope to gain a deeper understanding of the role that DSBs play in learning and memory—and in the disruption of these important brain functions by Alzheimer’s disease.”
Computer simulations yield clues to how cells interact with surroundings
Your cells are social butterflies. They constantly interact with their surroundings, taking in cues on when to divide and where to anchor themselves, among other critical tasks.
This networking is driven in part by proteins called integrin, which reside in a cell’s outer plasma membrane. Their job is to convert mechanical forces from outside the cell into internal chemical signals that tell the cell what to do. That is, when they work properly. When they misfire, integrins can cause diseases such as atherosclerosis and several types of cancer.
Despite their importance—good and bad—scientists don’t exactly know how integrins work. That’s because it’s very difficult to experimentally observe the protein’s molecular machinery in action. Scientists have yet to obtain the entire crystal structure of integrin within the plasma membrane, which is a go-to way to study a protein’s function. Roadblocks like this have ensured that integrins remain a puzzle despite years of research.
But what if there was another way to study integrin? One that doesn’t rely on experimental methods? Now there is, thanks to a computer model of integrin developed by Berkeley Lab researchers. Like its biological counterpart, the virtual integrin snippet is about twenty nanometers long. It also responds to changes in energy and other stimuli just as integrins do in real life. The result is a new way to explore how the protein connects a cell’s inner and outer environments.
“We can now run computer simulations that reveal how integrins in the plasma membrane translate external mechanical cues to chemical signals within the cell,” says Mohammad Mofrad, a faculty scientist in Berkeley Lab’s Physical Biosciences Division and associate professor of Bioengineering and Mechanical Engineering at UC Berkeley. He conducted the research with his graduate student Mehrdad Mehrbod.
They report their research in a recent issue of PLoS Computational Biology.
Their “molecular dynamics” model is the latest example of computational biology, in which scientists use computers to analyze biological phenomena for insights that may not be available via experiment. As you’d expect from a model that accounts for the activities of half a million atoms at once, the integrin model takes a lot of computing horsepower to pull off. Some of its simulations require 48 hours of run time on 600 parallel processors at the U.S. Department of Energy’s (DOE) National Energy Research Scientific Computing Center (NERSC), which is located at Berkeley Lab.
The model is already shedding light on what makes integrin tick, such as how they “know” to respond to more force with greater numbers. When activated by an external force, integrins cluster together on a cell’s surface and join other proteins to form structures called focal adhesions. These adhesions recruit more integrins when they’re subjected to higher forces. As the model indicates, this ability to pull in more integrins on demand may be due to the fact that a subunit of integrin is connected to actin filaments, which form a cell’s skeleton.
“We found that if actin filaments sustain more forces, they automatically bring more integrins together, forming a larger cluster,” says Mehrbod.
The model may also help answer a longstanding question: Do integrins interact with each other immediately after they’re activated? Or do they not interact with each other at all, even as they cluster together?
To find out, the scientists ran simulations that explored whether it’s physically possible for integrins to interact when they’re embedded in the plasma membrane. They found that interactions are likely to occur only between one compartment of integrin called the β-subunit.
They also discovered an interesting pattern in which integrins fluctuate. Two integrin sections, one that spans the cell membrane and one that protrudes from the cell, are connected by a hinge-like region. This hinge swings about when the protein is forced to vibrate as a result of frequent kicks from other molecules around it, such as water molecules, lipids, and ions.
These computationally obtained insights could guide new experiments designed to uncover how integrins do their job.
“Our research sets up an avenue for future studies by offering a hypothesis that relates integrin activation and clustering,” says Mofrad.
(Image: Two transmembrane integrin β-domains (in red) interact at their tails. The domains are embedded in a lipid layer that mimics the cell membrane. Credit: Mofrad lab)
Via thekidshouldseethis, a truly beautiful animated look that explains the simple elegance of DNA, and how, with just four bases at its disposal, it can code for everything that we are and everything that we know:
Director William Samuel and London-based studio Territory made this beautifully illustrated explainer of DNA for BBC Knowledge and Learning. Read more about their inspiration (hint!) and the BBC’s forthcoming site here.
via FastCoDesign.
Wow, what a great use of motion graphics to explain a very complex topic. Well done!
