Published by
Stanford Medicine

Category

Bioengineering

Bioengineering, Cardiovascular Medicine, Neuroscience, Research, Stanford News, Stroke

Targeted stimulation of specific brain cells boosts stroke recovery in mice

big blue brainThere are 525,949 minutes in a year. And every year, there are about 800,000 strokes in the United States – so, one stroke every 40 seconds. Aside from the infusion, within three or four hours of the stroke, of a costly biological substance called tissue plasminogen activator (whose benefit is less-than-perfectly established), no drugs have been shown to be effective in treating America’s largest single cause of neurologic disability and the world’s second-leading cause of death. (Even the workhorse post-stroke treatment, physical therapy, is far from a panacea.)

But a new study, led by Stanford neurosurgery pioneer Gary Steinberg and published in Proceedings of the National Academy of Sciences, may presage a better way to boost stroke recovery. In the study, Steinberg and his colleagues used a cutting-edge technology to directly stimulate movement-associated areas of the brains of mice that had suffered strokes.

Known as optogenetics – whose champion, Stanford psychiatrist and bioengineer Karl Deisseroth, co-authored the study – the light-driven method lets investigators pinpoint a specific set of nerve cells and stimulate only those cells. In contrast, the electrode-based brain stimulation devices now increasingly used for relieving symptoms of Parkinson’s disease, epilepsy and chronic pain also stimulate the cells’ near neighbors.

“We wanted to find out whether activating these nerve cells alone can contribute to recovery,” Steinberg told me.

As I wrote in a news release  about the study:

By several behavioral … and biochemical measures, the answer two weeks later was a strong yes. On one test of motor coordination, balance and muscular strength, the mice had to walk the length of a horizontal beam rotating on its axis, like a rotisserie spit. Stroke-impaired mice [in which the relevant brain region] was optogenetically stimulated did significantly better in how far they could walk along the beam without falling off and in the speed of their transit, compared with their unstimulated counterparts. The same treatment, applied to mice that had not suffered a stroke but whose brains had been … stimulated just as stroke-affected mice’s brains were, had no effect on either the distance they travelled along the rotating beam before falling off or how fast they walked. This suggests it was stimulation-induced repair of stroke damage, not the stimulation itself, yielding the improved motor ability.

Moreover, levels of some important natural substances called growth factors increased in a number of brain areas in  optogenetically stimulated but not unstimulated post-stroke mice. These factors are key to a number of nerve-cell repair processes. Interestingly, some of the increases occurred not only where stimulation took place but in equivalent areas on the opposite side of the brain, consistent with the idea that when we lose function on one side of the brain, the unaffected hemisphere can step in to help restore some of that lost function.

Translating these findings into human trials will mean not just brain surgery, but also gene therapy in order to introduce a critical light-sensitive protein into the targeted brain cells. Steinberg notes, though, that trials of gene therapy for other neurological disorders have already been conducted.

Previously: Brain sponge: Stroke treatment may extend time to prevent brain damage, BE FAST: Learn to recognize the signs of stroke and Light-switch seizure control? In a bright new study, researchers show how
Photo by Shutterstock.com

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Bioengineering, Stanford News

Foldscope inventor named one of the world’s top innovators under 35 by Technology Review

Foldscope inventor named one of the world's top innovators under 35 by Technology Review

Stanford bioengineer Manu Prakash, PhD, has said that he wants to make high-tech science available to the developing world. This year, his “frugal science” approach has earned him considerable media attention, culminating in today’s announcement that he has been named one of Technology Review’s 35 innovators under 35 (Prakash is 34).

Prakash’s busy year got its start in the spring, when a TED talk he had given about a 50 cent folding microscope was released. The microscope, called the Foldscope, folds like origami and is powerful enough to detect microbes and project the image on a wall or screen. Prakash later offered to give away 50,000 Foldscopes to people carrying out innovative projects around the world.

Soon after, Prakash won a competition to build a new science kit for kids, held by the Gordon and Betty Moore Foundation and the Society for Science & the Public. His entry was a sophisticated chemistry kit built out of a music box. In a story I wrote, Prakash said, “I’d started thinking about this connection between science education and global health. The things that you make for kids to explore science are also exactly the kind of things that you need in the field because they need to be robust and they need to be highly versatile.”

These accomplishments earned Prakash an invitation to the White House Makers Faire in June, where National Institutes of Health Director Francis Collins, MD,  PhD, had a chance to try the Foldscope. He wrote about the device in his blog, “Not only will Foldscope give healthcare workers around the globe better ways to detect, and thereby treat, disease, it will also place magnifying power within the reach of all the world’s students, enabling them to ask and answer a great many scientific questions.”

Technology Review described what made Prakash stand out:

Manu Prakash is determined to push down the cost of doing science. Expensive facilities, he says, limit knowledge and expertise to a privileged elite. So from his lab in Stanford’s bioengineering department, he’s producing instruments that enable people to undertake scientific explorations on the cheap.

Previously: Manu Prakash on how growing up in India influenced his interests as a Maker and entrepreneur, Dr. Prakash goes to Washington, The pied piper of cool science tools, Music box inspires a chemistry set for kids and scientists in developing countries and Free DIY microscope kits to citizen scientists with inspiring project ideas

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Applied Biotechnology, Bioengineering, Science, Stanford News, Technology

Manu Prakash on how growing up in India influenced his interests as a Maker and entrepreneur

Manu Prakash on how growing up in India influenced his  interests as a Maker and entrepreneur

foldscope_6.23.14Last week, Stanford bioengineer Manu Prakash, PhD, inventor of the 50-cent microscope, called the Foldscope, and a $5 chemistry kit, participated in the White House’s first-ever Maker Faire.

In a Q&A recently published on the White House blog, Prakash discusses what led him to become a Maker, his journey to the United States from India to pursue science and how he hopes his inventions will change the world. On the topic of how his immigrant roots influenced his interests as a Maker and entrepreneur, he says:

I recently started my own lab in the U.S. I decided to dedicate half of my time to frugal science (in the night time, I am a marine biophysicist). Because of growing up in a developing country context with very little resources, I naturally understand the scale of problems and the scale of solutions needed. But only by being in the hyperdrive mode of innovation in the U.S. do I have the tools at hand to actually tackle these challenges. So what I am as a Maker, an entrepreneur, and as an academic scientist is truly a juxtaposition/superposition of my experiences in these two countries.

Another common thread that my Indian roots taught me, which got strengthened by my experiences in the United States, is empathy. Without it, all the technological innovation in the world will not be utilized. It’s humans that make this incredible machine we call society run. The current society is truly global and we need to be global scientists.

Previously: Dr. Prakash goes to Washington, Stanford microscope inventor invited to first White House Maker Faire, The pied piper of cool science tools, Music box inspires a chemistry set for kids and scientists in developing countries and Free DIY microscope kits to citizen scientists with inspiring project ideas
Photo by @PrakashLab

Applied Biotechnology, Bioengineering, Science, Stanford News, Technology

Dr. Prakash goes to Washington

Dr. Prakash goes to Washington

Prakash at White House

It’s not every day that a researcher gets to hang out at the White House – so Wednesday was rather unusual for Stanford bioengineer Manu Prakash, PhD. Prakash, inventor of the 50-cent microscope, called the Foldscope, and a $5 chemistry kit, participated in the White House’s first-ever Maker Faire that day. He called it an “inspiring event” and tweeted the above photo from his time there.

And for those interested in learning more, a paper on the Foldscope was published online this week in PLOS One.

Previously: Stanford microscope inventor invited to first White House Maker Faire, The pied piper of cool science tools, Music box inspires a chemistry set for kids and scientists in developing countries, Free DIY microscope kits to citizen scientists with inspiring project ideas and Stanford bioengineer develops a 50-cent paper microscope
Photo by Manu Prakash

Bioengineering, Neuroscience, Sports, Stanford News

Mouthguard technology by Stanford bioengineers could improve concussion measurement

Mouthguard technology by Stanford bioengineers could improve concussion measurement

head impactPerhaps you’ve heard of helmet sensors to alert emergency contacts if a rider falls from a bicycle. Now, Stanford bioengineers are working with mouthguards that measure and report head impacts in football players in real time, and the research could have implications for understanding the forces of head traumas from more common accidents.

Stanford News reports:

For the past few years, David Camarillo, an assistant professor of bioengineering, and his colleagues have been supplying Stanford football players with special mouthguards equipped with accelerometers that measure the impacts players sustain during a practice or game. Previous studies have suggested a correlation between the severity of brain injuries and the biomechanics associated with skull movement from an impact.

Camarillo’s group uses a sensor-laden mouthguard because it can directly measure skull accelerations – by attaching to the top row of teeth – which is difficult to achieve with sensors attached to the skin or other tissues. So far, the researchers have recorded thousands of these impacts, and have found that players’ heads frequently sustain accelerations of 10 g forces, and, in rarer instances, as much as 100 g forces. By comparison, space shuttle astronauts experience a maximum of 3 g forces on launch and reentry.

Camarillo, PhD, and colleagues including bioengindeering doctoral student Lyndia Wu are enhancing the technology and refining the data collected, detecting head impacts in a lab test-dummy with 99 percent accuracy.  They’ve recently published a paper on their work in IEEE Transactions on Biomedical Engineering.

“Our football team has been extremely cooperative and interested in helping solve this problem,” Camarillo told writer Bjorn Carey. “What we are learning from them will help lead to technologies that will one day make bike riding and driving in your car safer too.”

Previously: Is repetitive heading in soccer a health hazard?Now that’s using your head: Bike-helmet monitor alerts emergency contacts after a crash and Stanford researchers working to combat concussions in football
Photo by Linda A. Cicero/Stanford News Service

Behavioral Science, Bioengineering, Neuroscience, Research, Stanford News, Technology

Party animal: Scientists nail “social circuit” in rodent brain (and probably ours, too)

Party animal: Scientists nail "social circuit" in rodent brain (and probably ours, too)

party animalStimulating a single nerve-cell circuit among millions in the brain instantly increases a mouse’s appetite for getting to know a strange mouse, while inhibiting it shuts down the same mouse’s drive to socialize with the stranger.

Stanford brain scientist and technology whiz Karl Deisseroth, MD, PhD, is already renowned for his role in developing optogenetics, a technology that allows researchers to turn on and turn off nerve-cell activity deep within the brain of a living, freely roving animal so they can see the effects of that switching in real time. He also pioneered CLARITY, a method of rendering the brain – at least if it’s the size of of a mouse’s – both transparent and porous so its anatomy can be charted, even down to the molecular level, in ways previously deemed unimaginable.

Now, in another feat of methodological derring-do detailed in a new study in Cell, Deisseroth and his teammates incorporated a suite of advanced lab technologies, including optogenetics as well as a couple of new tricks, to pinpoint a particular assembly of nerve cells projecting from one part to another part of the mouse brain. We humans’ brains obviously differ in some ways from those of mice. But our brains have the same connections Deisseroth’s group implicated in mice’s tendency to seek or avoid social contact. So it’s a good bet this applies to us, too.

Yes, we’d all like to be able to flip a switch and turn on our own “party animal” social circuitry from time to time. But the potential long-term applications of advances like this one are far from frivolous. The new findings may throw light on psychiatric disorders marked by impaired social interaction such as autism, social anxiety, schizophrenia and depression.From my release on this study:

“Every behavior presumably arises from a pattern of activity in the brain, and every behavioral malfunction arises from malfunctioning circuitry,” said Deisseroth, who is also co-director of Stanford’s Cracking the Neural Code Program. “The ability, for the first time, to pinpoint a particular nerve-cell projection involved in the social behavior of a living, moving animal will greatly enhance our ability to understand how social behavior operates, and how it can go wrong.”

Previously: Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, Researchers induce social deficits associated with autism, schizophrenia in mice, Anti-anxiety circuit found in unlikelybrain region and Using light to get muscles moving
Photo by Gamerscore blog

Applied Biotechnology, Bioengineering, Science, Science Policy, Stanford News

Stanford microscope inventor invited to first White House Maker Faire

Stanford microscope inventor invited to first White House Maker Faire

Foldscope-adams-squareLast week assistant professor of bioengineering Manu Prakash, PhD, received a call he couldn’t refuse — an invitation to attend the first-ever White House Maker Faire, to show attendees how to build a 50-cent microscope out of laser-cut paper, plastic tape and a tiny glass bead.

At today’s event, Prakash will also demonstrate how he turned a toy music box into a $5 programmable microfluidic chemistry set that can be used for applications as diverse as testing water quality and science fair projects.

Maker Faires, started by Make magazine in 2006, are gatherings where do-it-yourself enthusiasts show off their homemade projects and teach others how to make things using new technologies such as 3D printers, laser cutters, and desktop machine tools.

President Obama is hosting the first-ever White House Maker Faire to celebrate our “Nation of Makers” and to help empower America’s students and entrepreneurs to invent the future.

Prakash, who grew up in the mega-cities of India without a refrigerator, is a leader in the frugal maker movement. At Stanford, he works with students from bioengineering, medicine, and Bio-X to reengineer expensive, complex health-related devices to make them better, faster and cheaper.

His team also focuses on developing affordable science tools to inspire global innovation. To that end, Prakash recently launched an educational initiative called the “10,000 Microscopes Project,” where build-your-own-microscope kits will be shipped to the first 10,000 people who pledge to share their microscope images and experiments in a free, online microscopy manual.

“I’m so happy that the White House is looking at ways to celebrate scientific curiosity and invention,” Prakash told me. “Many children around the world have never used a microscope, even in developed countries like the United States. A universal program providing a microscope for every child could foster deep interest in science at an early age.”

For more information on the White House Maker Faire and today’s National Day of Making, or to watch the event live, visit www.whitehouse.gov/makerfaire or follow #NationofMakers on Twitter.

Previously: The pied piper of cool science tools, Music box inspires a chemistry set for kids and scientists in developing countries, Free DIY microscope kits to citizen scientists with inspiring project ideas and Stanford bioengineer develops a 50-cent paper microscope
Photo, of Quinn Monahan trying out a paper microscope, by Amy Adams
Photo in featured entry box by Manu Prakash

Bioengineering, Genetics, Neuroscience, Pregnancy, Research, Stanford News

Step away from the DNA? Circulating *RNA* in blood gives dynamic information about pregnancy, health

Step away from the DNA? Circulating *RNA* in blood gives dynamic information about pregnancy, health

blood on fingertip - 260

I read a lot of scientific papers. And while they’re all interesting, they don’t all make me snap to attention like the latest from Stanford bioengineer Stephen Quake, PhD. I even remarked to my husband that it’s rare to get the immediate sense that a discovery will significantly change clinical care.

If anyone’s going to shake up the status quo, however, it would be Quake. You may remember that Quake has made waves before with his pioneering discoveries involving the analysis of tiny bits of DNA circulating in our blood. His 2008 discovery that it’s possible to non-invasively detect fetal chromosomal abnormalities with a maternal blood sample has revolutionized prenatal care in this country. It’s estimated that, in 2013, hundreds of thousands of pregnant women used a version of this test to learn more about the health of their fetuses. And, in 2012, Quake showed its possible to sequence an entire fetal genome from a maternal blood sample.

Now he and his lab have gone one step further by turning their attention to another genetic material in the blood, RNA. Although information conveyed in the form of DNA sequences is mostly static (the nucleotide sequence of genes, for example), RNA levels and messages change markedly among tissues over time and at various developmental points. The difference in available information is somewhat like comparing a still photo with a high-resolution video when it comes to sussing out what the body is actually doing at any point in time.

The study was published today in the Proceedings of the National Academy of Sciences. As I explain in my release:

In the new study, the researchers used a technique previously developed in Quake’s lab to identify which circulating RNA molecules in a pregnant woman were likely to have come from her fetus, and which were from her own organs. They found they were able to trace the development of specific tissues, including the fetal brain and liver, as well as the placenta, during the three trimesters of pregnancy simply by analyzing blood samples from the pregnant women over time.

Quake and his colleagues believe the technique could also be broadly useful as a diagnostic tool by detecting distress signals from diseased organs, perhaps even before any clinical symptoms are apparent. In particular, they found they could detect elevated levels of neuronal-specific RNA messages in people with Alzheimer’s disease as compared with the healthy participants.

Quake and the lead authors, graduate students Winston Koh and Wenying Pan, liken their technique to a “molecular stethoscope.” They believe it could be broadly useful in the clinic. More from my release:

“We’ve moved beyond just detecting gene sequences to really analyzing and understanding patterns of gene activity,” said Quake. “Knowing the DNA sequence of a gene in the blood has been shown to be useful in a few specific cases, like cancer, pregnancy and organ transplantation. Analyzing the RNA enables a much broader perspective of what’s going on in the body at any particular time.”

Previously: Whole-genome fetal sequencing recognized as one of the year’s “10 Breakthrough Technologies” and Better know a bioengineer: Stephen Quake
Photo by Alden Chadwick

Bioengineering, Research, Stanford News, Technology

An advancement in optogenetics: Switching off cells with light now as easy as switching them on

An advancement in optogenetics: Switching off cells with light now as easy as switching them on

Earlier this week, the New York Times featured Karl Deisseroth, MD, PhD, and his work in optogenetics, which involves precisely turning select brain cells on or off with flashes of light. Today, Deisseroth and colleagues share in the journal Science an advancement in the field. As Tom Abate explains in a release:

Optogenetics gave researchers a powerful investigational technique to deepen their understanding of biological system design and function in animal models. But first-generation optogenetics had a shortcoming: Its light-sensitive proteins were potent at switching cells on, but less effective at turning them off.

Now in a paper culminating years of effort, Deisseroth’s team has re-engineered their light-sensitive proteins to switch cells off far more efficiently than before…

“This is something we and others in the field have sought for a very long time,” said Deisseroth, senior author of the paper and professor of bioengineering and of psychiatry and behavioral sciences.

Thomas Insel, MD, director of the National Institute of Mental Health, which funded the study, said this improved “off” switch will help researchers to better understand the brain circuits involved in behavior, thinking and emotion.

“This latest discovery by the Deisseroth team is the kind of neurotechnology envisioned by President Obama when he launched the BRAIN Initiative a year ago,” Insel said. “It creates a powerful tool that allows neuroscientists to apply a brake in any specific circuit with millisecond precision, beyond the power of any existing technology.”

The release offers more details on the work and its implications.

Previously: New York Times profiles Stanford’s Karl Deisseroth and his work in optogenetics, A federal push to further brain research, An in-depth look at the career of Stanford’s Karl Deisseroth, “a major name in science”, Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, The “rock star” work of Stanford’s Karl Deisseroth and Nature Methods names optogenetics its “Method of the Year
Related: Head lights

Bioengineering, In the News, Neuroscience, Stanford News, Technology

New York Times profiles Stanford’s Karl Deisseroth and his work in optogenetics

New York Times profiles Stanford's Karl Deisseroth and his work in optogenetics

Rockefeller University neurobiologist Cori Bargmann, PhD, is quoted in today’s New York Times as saying optogenetics is “the most revolutionary thing that has happened in neuroscience in the past couple of decades.” The article is a profile piece of Karl Deisseroth, MD, PhD, the Stanford researcher who helped create the field of optogenetics, and it reveals how a clinical rotation in psychiatry led him to this line of work:

It was eye-opening, he said, “to sit and talk to a person whose reality is different from yours” — to be face to face with the effects of bipolar disorder, “exuberance, charisma, love of life, and yet, how destructive”; of depression, “crushing — it can’t be reasoned with”; of an eating disorder literally killing a young, intelligent person, “as if there’s a conceptual cancer in the brain.”

He saw patient after patient suffering terribly, with no cure in sight. “It was not as if we had the right tools or the right understanding.” But, he said, that such tools were desperately needed made it more interesting to him as a specialty. He stayed with psychiatry, but adjusted his research course, getting in on the ground floor in a new bioengineering department at Stanford. He is now a professor of both bioengineering and psychiatry.

Previously: A federal push to further brain research, An in-depth look at the career of Stanford’s Karl Deisseroth, “a major name in science”, Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, The “rock star” work of Stanford’s Karl Deisseroth and Nature Methods names optogenetics its “Method of the Year
Related: Head lights
Photo in featured-entry box by Linda Cicero/Stanford News Service

Stanford Medicine Resources: