Tag Archives: cells

#437202 Scientists Used Dopamine to Seamlessly ...

In just half a decade, neuromorphic devices—or brain-inspired computing—already seem quaint. The current darling? Artificial-biological hybrid computing, uniting both man-made computer chips and biological neurons seamlessly into semi-living circuits.

It sounds crazy, but a new study in Nature Materials shows that it’s possible to get an artificial neuron to communicate directly with a biological one using not just electricity, but dopamine—a chemical the brain naturally uses to change how neural circuits behave, most known for signaling reward.

Because these chemicals, known as “neurotransmitters,” are how biological neurons functionally link up in the brain, the study is a dramatic demonstration that it’s possible to connect artificial components with biological brain cells into a functional circuit.

The team isn’t the first to pursue hybrid neural circuits. Previously, a different team hooked up two silicon-based artificial neurons with a biological one into a circuit using electrical protocols alone. Although a powerful demonstration of hybrid computing, the study relied on only one-half of the brain’s computational ability: electrical computing.

The new study now tackles the other half: chemical computing. It adds a layer of compatibility that lays the groundwork not just for brain-inspired computers, but also for brain-machine interfaces and—perhaps—a sort of “cyborg” future. After all, if your brain can’t tell the difference between an artificial neuron and your own, could you? And even if you did, would you care?

Of course, that scenario is far in the future—if ever. For now, the team, led by Dr. Alberto Salleo, professor of materials science and engineering at Stanford University, collectively breathed a sigh of relief that the hybrid circuit worked.

“It’s a demonstration that this communication melding chemistry and electricity is possible,” said Salleo. “You could say it’s a first step toward a brain-machine interface, but it’s a tiny, tiny very first step.”

Neuromorphic Computing
The study grew from years of work into neuromorphic computing, or data processing inspired by the brain.

The blue-sky idea was inspired by the brain’s massive parallel computing capabilities, along with vast energy savings. By mimicking these properties, scientists reasoned, we could potentially turbo-charge computing. Neuromorphic devices basically embody artificial neural networks in physical form—wouldn’t hardware that mimics how the brain processes information be even more efficient and powerful?

These explorations led to novel neuromorphic chips, or artificial neurons that “fire” like biological ones. Additional work found that it’s possible to link these chips up into powerful circuits that run deep learning with ease, with bioengineered communication nodes called artificial synapses.

As a potential computing hardware replacement, these systems have proven to be incredibly promising. Yet scientists soon wondered: given their similarity to biological brains, can we use them as “replacement parts” for brains that suffer from traumatic injuries, aging, or degeneration? Can we hook up neuromorphic components to the brain to restore its capabilities?

Buzz & Chemistry
Theoretically, the answer’s yes.

But there’s a huge problem: current brain-machine interfaces only use electrical signals to mimic neural computation. The brain, in contrast, has two tricks up its sleeve: electricity and chemicals, or electrochemical.

Within a neuron, electricity travels up its incoming branches, through the bulbous body, then down the output branches. When electrical signals reach the neuron’s outgoing “piers,” dotted along the output branch, however, they hit a snag. A small gap exists between neurons, so to get to the other side, the electrical signals generally need to be converted into little bubble ships, packed with chemicals, and set sail to the other neuronal shore.

In other words, without chemical signals, the brain can’t function normally. These neurotransmitters don’t just passively carry information. Dopamine, for example, can dramatically change how a neural circuit functions. For an artificial-biological hybrid neural system, the absence of chemistry is like nixing international cargo vessels and only sticking with land-based trains and highways.

“To emulate biological synaptic behavior, the connectivity of the neuromorphic device must be dynamically regulated by the local neurotransmitter activity,” the team said.

Let’s Get Electro-Chemical
The new study started with two neurons: the upstream, an immortalized biological cell that releases dopamine; and the downstream, an artificial neuron that the team previously introduced in 2017, made of a mix of biocompatible and electrical-conducting materials.

Rather than the classic neuron shape, picture more of a sandwich with a chunk bitten out in the middle (yup, I’m totally serious). Each of the remaining parts of the sandwich is a soft electrode, made of biological polymers. The “bitten out” part has a conductive solution that can pass on electrical signals.

The biological cell sits close to the first electrode. When activated, it dumps out boats of dopamine, which drift to the electrode and chemically react with it—mimicking the process of dopamine docking onto a biological neuron. This, in turn, generates a current that’s passed on to the second electrode through the conductive solution channel. When this current reaches the second electrode, it changes the electrode’s conductance—that is, how well it can pass on electrical information. This second step is analogous to docked dopamine “ships” changing how likely it is that a biological neuron will fire in the future.

In other words, dopamine release from the biological neuron interacts with the artificial one, so that the chemicals change how the downstream neuron behaves in a somewhat lasting way—a loose mimic of what happens inside the brain during learning.

But that’s not all. Chemical signaling is especially powerful in the brain because it’s flexible. Dopamine, for example, only grabs onto the downstream neurons for a bit before it returns back to its upstream neuron—that is, recycled or destroyed. This means that its effect is temporary, giving the neural circuit breathing room to readjust its activity.

The Stanford team also tried reconstructing this quirk in their hybrid circuit. They crafted a microfluidic channel that shuttles both dopamine and its byproduct away from the artificial neurons after they’ve done their job for recycling.

Putting It All Together
After confirming that biological cells can survive happily on top of the artificial one, the team performed a few tests to see if the hybrid circuit could “learn.”

They used electrical methods to first activate the biological dopamine neuron, and watched the artificial one. Before the experiment, the team wasn’t quite sure what to expect. Theoretically, it made sense that dopamine would change the artificial neuron’s conductance, similar to learning. But “it was hard to know whether we’d achieve the outcome we predicted on paper until we saw it happen in the lab,” said study author Scott Keene.

On the first try, however, the team found that the burst of chemical signaling was able to change the artificial neuron’s conductance long-term, similar to the neuroscience dogma “neurons that fire together, wire together.” Activating the upstream biological neuron with chemicals also changed the artificial neuron’s conductance in a way that mimicked learning.

“That’s when we realized the potential this has for emulating the long-term learning process of a synapse,” said Keene.

Visualizing under an electron microscope, the team found that, similar to its biological counterpart, the hybrid synapse was able to efficiently recycle dopamine with timescales similar to the brain after some calibration. By playing with how much dopamine accumulates at the artificial neuron, the team found that they loosely mimic a learning rule called spike learning—a darling of machine learning inspired by the brain’s computation.

A Hybrid Future?
Unfortunately for cyborg enthusiasts, the work is still in its infancy.

For one, the artificial neurons are still rather bulky compared to biological ones. This means that they can’t capture and translate information from a single “boat” of dopamine. It’s also unclear if, and how, a hybrid synapse can work inside a living brain. Given the billions of synapses firing away in our heads, it’ll be a challenge to find-and-replace those that need replacement, and be able to control our memories and behaviors similar to natural ones.

That said, we’re inching ever closer to full-capability artificial-biological hybrid circuits.

“The neurotransmitter-mediated neuromorphic device presented in this work constitutes a fundamental building block for artificial neural networks that can be directly modulated based on biological feedback from live neurons,” the authors concluded. “[It] is a crucial first step in realizing next-generation adaptive biohybrid interfaces.”

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#437171 Scientists Tap the World’s Most ...

In The Hitchhiker’s Guide to the Galaxy by Douglas Adams, the haughty supercomputer Deep Thought is asked whether it can find the answer to the ultimate question concerning life, the universe, and everything. It replies that, yes, it can do it, but it’s tricky and it’ll have to think about it. When asked how long it will take it replies, “Seven-and-a-half million years. I told you I’d have to think about it.”

Real-life supercomputers are being asked somewhat less expansive questions but tricky ones nonetheless: how to tackle the Covid-19 pandemic. They’re being used in many facets of responding to the disease, including to predict the spread of the virus, to optimize contact tracing, to allocate resources and provide decisions for physicians, to design vaccines and rapid testing tools, and to understand sneezes. And the answers are needed in a rather shorter time frame than Deep Thought was proposing.

The largest number of Covid-19 supercomputing projects involves designing drugs. It’s likely to take several effective drugs to treat the disease. Supercomputers allow researchers to take a rational approach and aim to selectively muzzle proteins that SARS-CoV-2, the virus that causes Covid-19, needs for its life cycle.

The viral genome encodes proteins needed by the virus to infect humans and to replicate. Among these are the infamous spike protein that sniffs out and penetrates its human cellular target, but there are also enzymes and molecular machines that the virus forces its human subjects to produce for it. Finding drugs that can bind to these proteins and stop them from working is a logical way to go.

The Summit supercomputer at Oak Ridge National Laboratory has a peak performance of 200,000 trillion calculations per second—equivalent to about a million laptops. Image credit: Oak Ridge National Laboratory, U.S. Dept. of Energy, CC BY

I am a molecular biophysicist. My lab, at the Center for Molecular Biophysics at the University of Tennessee and Oak Ridge National Laboratory, uses a supercomputer to discover drugs. We build three-dimensional virtual models of biological molecules like the proteins used by cells and viruses, and simulate how various chemical compounds interact with those proteins. We test thousands of compounds to find the ones that “dock” with a target protein. Those compounds that fit, lock-and-key style, with the protein are potential therapies.

The top-ranked candidates are then tested experimentally to see if they indeed do bind to their targets and, in the case of Covid-19, stop the virus from infecting human cells. The compounds are first tested in cells, then animals, and finally humans. Computational drug discovery with high-performance computing has been important in finding antiviral drugs in the past, such as the anti-HIV drugs that revolutionized AIDS treatment in the 1990s.

World’s Most Powerful Computer
Since the 1990s the power of supercomputers has increased by a factor of a million or so. Summit at Oak Ridge National Laboratory is presently the world’s most powerful supercomputer, and has the combined power of roughly a million laptops. A laptop today has roughly the same power as a supercomputer had 20-30 years ago.

However, in order to gin up speed, supercomputer architectures have become more complicated. They used to consist of single, very powerful chips on which programs would simply run faster. Now they consist of thousands of processors performing massively parallel processing in which many calculations, such as testing the potential of drugs to dock with a pathogen or cell’s proteins, are performed at the same time. Persuading those processors to work together harmoniously is a pain in the neck but means we can quickly try out a lot of chemicals virtually.

Further, researchers use supercomputers to figure out by simulation the different shapes formed by the target binding sites and then virtually dock compounds to each shape. In my lab, that procedure has produced experimentally validated hits—chemicals that work—for each of 16 protein targets that physician-scientists and biochemists have discovered over the past few years. These targets were selected because finding compounds that dock with them could result in drugs for treating different diseases, including chronic kidney disease, prostate cancer, osteoporosis, diabetes, thrombosis and bacterial infections.

Scientists are using supercomputers to find ways to disable the various proteins—including the infamous spike protein (green protrusions)—produced by SARS-CoV-2, the virus responsible for Covid-19. Image credit: Thomas Splettstoesser scistyle.com, CC BY-ND

Billions of Possibilities
So which chemicals are being tested for Covid-19? A first approach is trying out drugs that already exist for other indications and that we have a pretty good idea are reasonably safe. That’s called “repurposing,” and if it works, regulatory approval will be quick.

But repurposing isn’t necessarily being done in the most rational way. One idea researchers are considering is that drugs that work against protein targets of some other virus, such as the flu, hepatitis or Ebola, will automatically work against Covid-19, even when the SARS-CoV-2 protein targets don’t have the same shape.

Our own work has now expanded to about 10 targets on SARS-CoV-2, and we’re also looking at human protein targets for disrupting the virus’s attack on human cells. Top-ranked compounds from our calculations are being tested experimentally for activity against the live virus. Several of these have already been found to be active.The best approach is to check if repurposed compounds will actually bind to their intended target. To that end, my lab published a preliminary report of a supercomputer-driven docking study of a repurposing compound database in mid-February. The study ranked 8,000 compounds in order of how well they bind to the viral spike protein. This paper triggered the establishment of a high-performance computing consortium against our viral enemy, announced by President Trump in March. Several of our top-ranked compounds are now in clinical trials.

Also, we and others are venturing out into the wild world of new drug discovery for Covid-19—looking for compounds that have never been tried as drugs before. Databases of billions of these compounds exist, all of which could probably be synthesized in principle but most of which have never been made. Billion-compound docking is a tailor-made task for massively parallel supercomputing.

Dawn of the Exascale Era
Work will be helped by the arrival of the next big machine at Oak Ridge, called Frontier, planned for next year. Frontier should be about 10 times more powerful than Summit. Frontier will herald the “exascale” supercomputing era, meaning machines capable of 1,000,000,000,000,000,000 calculations per second.

Although some fear supercomputers will take over the world, for the time being, at least, they are humanity’s servants, which means that they do what we tell them to. Different scientists have different ideas about how to calculate which drugs work best—some prefer artificial intelligence, for example—so there’s quite a lot of arguing going on.

Hopefully, scientists armed with the most powerful computers in the world will, sooner rather than later, find the drugs needed to tackle Covid-19. If they do, then their answers will be of more immediate benefit, if less philosophically tantalizing, than the answer to the ultimate question provided by Deep Thought, which was, maddeningly, simply 42.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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#437109 This Week’s Awesome Tech Stories From ...

FUTURE
Why the Coronavirus Is So Confusing
Ed Yong | The Atlantic
“…beyond its vast scope and sui generis nature, there are other reasons the pandemic continues to be so befuddling—a slew of forces scientific and societal, epidemiological and epistemological. What follows is an analysis of those forces, and a guide to making sense of a problem that is now too big for any one person to fully comprehend.”

ARTIFICIAL INTELLIGENCE
Common Sense Comes Closer to Computers
John Pavlus | Quanta Magazine
“The problem of common-sense reasoning has plagued the field of artificial intelligence for over 50 years. Now a new approach, borrowing from two disparate lines of thinking, has made important progress.”

BIOTECH
Scientists Create Glowing Plants Using Bioluminescent Mushroom DNA
George Dvorsky | Gizmodo
“New research published today in Nature Biotechnology describes a new technique, in which the DNA from bioluminescent mushrooms was used to create plants that glow 10 times brighter than their bacteria-powered precursors. Botanists could eventually use this technique to study the inner workings of plants, but it also introduces the possibility of glowing ornamental plants for our homes.”

HEALTH
Old Drugs May Find a New Purpose: Fighting the Coronavirus
Carl Zimmer | The New York Times
“Driven by the pandemic’s spread, research teams have been screening thousands of drugs to see if they have this unexpected potential to fight the coronavirus. They’ve tested the drugs on dishes of cells, and a few dozen candidates have made the first cut.”

MACHINE LEARNING
OpenAI’s New Experiments in Music Generation Create an Uncanny Valley Elvis
Devin Coldewey | TechCrunch
“AI-generated music is a fascinating new field, and deep-pocketed research outfit OpenAI has hit new heights in it, creating recreations of songs in the style of Elvis, 2Pac and others. The results are convincing, but fall squarely in the unnerving ‘uncanny valley’ of audio, sounding rather like good, but drunk, karaoke heard through a haze of drugs.”

CULTURE
Neural Net-Generated Memes Are One of the Best Uses of AI on the Internet
Jay Peters | The Verge
“I’ve spent a good chunk of my workday so far creating memes thanks to this amazing website from Imgflip that automatically generates captions for memes using a neural network. …You can pick from 48 classic meme templates, including distracted boyfriend, Drake in ‘Hotline Bling,’ mocking Spongebob, surprised Pikachu, and Oprah giving things away.”

GENETICS
Can Genetic Engineering Bring Back the American Chestnut?
Gabriel Popkin | The New York Times Magazine
“The geneticists’ research forces conservationists to confront, in a new and sometimes discomfiting way, the prospect that repairing the natural world does not necessarily mean returning to an unblemished Eden. It may instead mean embracing a role that we’ve already assumed: engineers of everything, including nature.”

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#436962 Scientists Engineered Neurons to Make ...

Electricity plays a surprisingly powerful role in our bodies. While most people are aware that it plays a crucial role in carrying signals to and from our nerves, our bodies produce electric fields that can do everything from helping heal wounds to triggering the release of hormones.

Electric fields can influence a host of important cellular behavior, like directional migration, proliferation, division, or even differentiation into different cell types. The work of Michael Levin at Tufts University even suggests that electrical fields may play a crucial role in the way our bodies organize themselves.

This has prompted considerable interest in exploiting our body’s receptiveness to electrical stimulation for therapeutic means, but given the diffuse nature of electrical fields a key challenge is finding a way to localize these effects. Conductive polymers have proven a useful tool in this regard thanks to their good electrical properties and biocompatibility, and have been used in everything from neural implants to biosensors.

But now, a team at Stanford University has developed a way to genetically engineer neurons to build the materials into their own cell membranes. The approach could make it possible to target highly specific groups of cells, providing unprecedented control over the body’s response to electrical stimulation.

In a paper in Science, the team explained how they used re-engineered viruses to deliver DNA that hijacks cells’ biosynthesis machinery to create an enzyme that assembles electroactive polymers onto their membranes. This changes the electrical properties of the cells, which the team demonstrated could be used to control their behavior.

They used the approach to modulate neuronal firing in cultures of rat hippocampal neurons, mouse brain slices, and even human cortical spheroids. Most impressively, they showed that they could coax the neurons of living C. elegans worms to produce the polymers in large enough quantities to alter their behavior without impairing the cells’ natural function.

Translating the idea to humans poses major challenges, not least because the viruses used to deliver the genetic changes are still a long way from being approved for clinical use. But the ability to precisely target specific cells using a genetic approach holds enormous promise for bioelectronic medicine, Kevin Otto and Christine Schmidt from the University of Florida say in an accompanying perspective.

Interest is booming in therapies that use electrical stimulation of neural circuits as an alternative to drugs for diseases as varied as arthritis, Alzheimer’s, diabetes, and cardiovascular disease, and hundreds of clinical trials are currently underway.

At present these approaches rely on electrodes that can provide some level of localization, but because different kinds of nerve cells are often packed closely together it’s proven hard to stimulate exactly the right nerves, say Otto and Schmidt. This new approach makes it possible to boost the conductivity of specific cell types, which could make these kinds of interventions dramatically more targeted.

Besides disease-focused bioelectronic interventions, Otto and Schmidt say the approach could prove invaluable for helping to interface advanced prosthetics with patients’ nervous systems by making it possible to excite sensory neurons without accidentally triggering motor neurons, or vice versa.

More speculatively, the approach could one day help create far more efficient bridges between our minds and machines. One of the major challenges for brain-machine interfaces is recording from specific neurons, something that a genetically targeted approach might be able to help greatly with.

If the researchers can replicate the ability to build electronic-tissue “composites” in humans, we may be well on our way to the cyborg future predicted by science fiction.

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#436784 This Week’s Awesome Tech Stories From ...

COMPUTING
Inside the Race to Build the Best Quantum Computer on Earth
Gideon Lichfield | MIT Technology Review
“Regardless of whether you agree with Google’s position [on ‘quantum supremacy’] or IBM’s, the next goal is clear, Oliver says: to build a quantum computer that can do something useful. …The trouble is that it’s nearly impossible to predict what the first useful task will be, or how big a computer will be needed to perform it.”

FUTURE
We’re Not Prepared for the End of Moore’s Law
David Rotman | MIT Technology Review
“Quantum computing, carbon nanotube transistors, even spintronics, are enticing possibilities—but none are obvious replacements for the promise that Gordon Moore first saw in a simple integrated circuit. We need the research investments now to find out, though. Because one prediction is pretty much certain to come true: we’re always going to want more computing power.”

ROBOTICS
Flippy the Burger-Flipping Robot Is Changing the Face of Fast Food as We Know It
Luke Dormehl | Digital Trends
“Flippy is the result of the Miso team’s robotics expertise, coupled with that industry-specific knowledge. It’s a burger-flipping robot arm that’s equipped with both thermal and regular vision, which grills burgers to order while also advising human collaborators in the kitchen when they need to add cheese or prep buns for serving.”

BIOTECHNOLOGY
The Next Generation of Batteries Could Be Built by Viruses
Daniel Oberhaus | Wired
“[MIT bioengineering professor Angela Belcher has] made viruses that can work with over 150 different materials and demonstrated that her technique can be used to manufacture other materials like solar cells. Belcher’s dream of zipping around in a ‘virus-powered car’ still hasn’t come true, but after years of work she and her colleagues at MIT are on the cusp of taking the technology out of the lab and into the real world.”

SPACE
Biggest Cosmic Explosion Ever Detected Left Huge Dent in Space
Hannah Devlin | The Guardian
“The biggest cosmic explosion on record has been detected—an event so powerful that it punched a dent the size of 15 Milky Ways in the surrounding space. The eruption is thought to have originated at a supermassive black hole in the Ophiuchus galaxy cluster, which is about 390 million light years from Earth.”

SCIENCE FICTION
Star Trek’s Warp Speed Would Have Tragic Consequences
Cassidy Ward | SyFy
“The various crews of Trek‘s slate of television shows and movies can get from here to there without much fanfare. Seeking out new worlds and new civilizations is no more difficult than gassing up the car and packing a cooler full of junk food. And they don’t even need to do that! The replicators will crank out a bologna sandwich just like mom used to make. All that’s left is to go, but what happens then?”

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