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Science is like an ongoing mystery novel, says Stanford neurobiologist Carla Shatz

Carla Shatz

We all know that Carla Shatz, PhD, director of the interdisciplinary institute Stanford Bio-X, is a pioneering scientist — her work in early brain development and in Alzheimer’s disease has earned her many accolades. Now she’s being featured in a videos series celebrating women pioneers in science.

I want to say first that it always rankles a bit when people are celebrated as being “pioneering women in XXX”. That makes it seem like if they weren’t women they wouldn’t have made the pioneer cut. Carla is a pioneer period. And also a woman. And gave a great interview.

One interesting point she made had to do with what she wished she’d known before starting a career in science. She said, “If you really like science and you like research, that is the joy and the easy part. The hard part is managing the teams and the research itself – the people.”

She went on to talk about the people who influenced her (her dad) and her first scientific experiment (it had to do with Siamese cats, and initially didn’t work).

When it comes to women in science, her answer was straightforward. She said we need talented people working on critical problems, and women are half the population. Without them, there are fewer people working on these important questions. She also said that she worries about the diminished funding for science driving the best minds (male and female) into other fields.

Her answer to what gets her up in the morning should help lure at least a few of those potential best minds into a scientific career, even with weak funding. She said:

Every day when I come to work I am so excited to be here and go to my lab and do experiments and be with my students. It’s part of an ongoing mystery. I can hardly wait to see the next part of the mystery that is going to be solved.

The series is sponsored by Scientista, which supports women in math and science, The Scientist magazine, Lab Manager and Mettler Toledo.

Previously: They said “Yes”: The attitude that defines Stanford Bio-X and Pioneers in science
Photo be Steve Fisch

Bioengineering, Research, Stanford News, Technology

Proteins from pond scum revolutionize neuroscience

Proteins from pond scum revolutionize neuroscience

pond scum smallI wrote a story recently about a cool technique called optogenetics, developed by bioengineering professor Karl Deisseroth, MD, PhD. He won the Keio Prize in Medicine, and I thought it might be interesting to talk with some other neuroscientists at Stanford to get their take on the importance of the technology. You know something is truly groundbreaking when each and every person you interview uses the word “revolutionary” to describe it.

Optogenetics is a technique that allows scientists to use light to turn particular nerves on or off. In the process, they’re learning new things about how the brain works and about diseases and mental health conditions like Parkinson’s disease, addiction and depression.

In describing the award, the Keio Prize committee wrote:

By making optogenetics a reality and leading this new field, Dr. Deisseroth has made enormous contributions towards the fundamental understanding of brain functions in health and disease.

One of the things I found most interesting when writing the story came from a piece Deisseroth wrote several years ago in Scientific American in which he stressed the importance of basic research. Optogenetics would not have been a reality without discoveries made in the lowly algae that makes up pond scum.

“The more directed and targeted research becomes, the more likely we are to slow our progress, and the more certain it is that the distant and untraveled realms, where truly disruptive ideas can arise, will be utterly cut off from our common scientific journey,” Deisseroth wrote.

Deisseroth told me that we need to be funding basic, curiosity-driven research along with efforts to make those discoveries relevant. He said that kind of translation is part of the value of  programs like Stanford Bio-X – an interdisciplinary institute founded in 1998 – which puts diverse faculty members side by side to enable that translation from basic science to medical discovery.

Previously: They said “Yes”: The attitude that defines Stanford Bio-X, New York Times profiles Stanford’s Karl Deisseroth and his work in optogenetics, 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
Photo by Tim Elliott, Shutterstock photos

Neuroscience, Research, Stanford News

Brain’s wiring more dynamic than originally thought

Brain's wiring more dynamic than originally thought

brain branches

I write a lot about news developments in which scientists learn new things about the body – how diseases develop or can be treated, how genes and proteins in our bodies make us who we are, how different areas of the brain work together to help us learn, remember and interact with our environment.

Yesterday I wrote a story in which the scientists learned that they have more work to do.

It all started when Joanna Mattis was looking for a PhD project. She had been working  in the lab of bioengineer Karl Deisseroth, MD, PhD, helping to develop optogenetics. At the time, that was an entirely new tool that scientists could use to turn parts of the brain on and off to see what happens. Mattis wanted to use optogenetics to map the wiring of two regions of the brain that were known to work together to help develop a spatial map of the environment. Those two regions are known as the hippocampus and the septum.

Some of the expertise needed to do this project didn’t exist in the Deisseroth lab. Mattis got a fellowship through Stanford Bio-X that specifically allows students to work with multiple mentors  – Mattis added neuroscientist John Huguenard, PhD, – bringing interdisciplinary expertise together to solve problems. In this case, those combined expertise didn’t so much solve a problem as create a new one.

What they found is that nerves in the hippocampus create one reaction in the septum if they fire slowly and a completely different reaction of they fire quickly. It was like learning that the wiring diagram of the brain shifts depending on how the brain sends signals.

Mattis told me, “There’s a lot of excitement about being able to make a map of the brain with the idea that if we could figure out how it is all connected we could understand how it works. It turns out it’s so much more dynamic than that.”

She said that next steps will include learning how widespread this type of wiring is throughout the brain, and understanding how it ties back to learning and memory.

Previously: Optogenetics: Offering new insights into brain disorders
Photo by nednapa/Shutterstock

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.

Research, Science, Stanford News

They said “Yes”: The attitude that defines Stanford Bio-X

They said "Yes": The attitude that defines Stanford Bio-X

bio-X peopleI write a lot about interdisciplinary research (it’s my job), but it was just recently that I heard the best description of what it is that makes interdisciplinary collaborations possible. It came from Carla Shatz, PhD, who directs Stanford Bio-X — an interdisciplinary institute founded in 1998 that brings together faculty from the schools of medicine, humanities & sciences and engineering. She told me:

You have to be able to walk into someone’s lab and say, “You know, I have this problem in my lab. Would you like to have a cup of coffee and talk about it?” And then that person needs to say, “Yes.”

We were talking about a recent report by the National Research Council of the National Academies. They had put together a workshop and then published a report giving advice and best practices for supporting interdisciplinary research. The report used Bio-X as a success story for the type of innovation that can come out of programs that cross disciplines.

Nowhere in the report is there a subhead reading, “Faculty have to say yes,” but a lot of the other advice is straight out of the Bio-X playbook. The institute needs to be located at the cross section of several schools or departments (check). The institute needs a building that brings people together (check). The institute needs to support students (check). The institute needs to be a financial value add rather than taxing participating departments (check).

This isn’t specifically called out in the report, but Shatz added that a good interdisciplinary institute also needs good food. She pointed out that people come from all over campus to eat at Nexus, located in the middle of the Clark Center that houses Bio-X and serves as a focus for its activities. It turns out scientists are just like the rest of us: offer good food and they will come. And then they will chat, and the next thing you know they’ll be collaborating.

I wrote a Q&A with Shatz based on our conversation. From now on, when I hear the phrase “She said yes” I’ll think of her, and her great description of the attitude that underlies collaboration.

Previously: Bio-X Kids Science Day inspires young scientists, Dinners spark neuroscience conversation, collaboration, Stanford’s Clark Center, home to Bio-X, turns 10 and Pioneers in science
Photo from Bio-X

Behavioral Science, Neuroscience, Stanford News

Real time view of changing minds

Real time view of changing minds

There at this morning’s meeting was a large box of donuts which I had absolutely no intention of eating. None. Until I changed my mind.

What happened this morning was probably a little more complex than the simple changes of mind that Stanford Neurosciences Institute director William Newsome studies, what with the delicious smell of chocolate and a quick realization that perhaps a lunchtime run could be squeezed into my day.

Newsome has focused on recording the activity of individual neurons in animals making simple decisions, like indicating which way a dot is moving on a screen. He and his team then statistically analyze the results of many such recordings of individual neurons. These studies have gone a long way toward revealing the activity of neurons in different parts of the brain but can miss some of the fine scale dynamics that take place during the decision-making process. Recently, new probes have been developed that allow scientists to record the activity of many neurons at the same time.

Using such a probe, Newsome and his team recorded groups of neurons in animals making simple decisions, and could track in real time the patterns of how the neurons fired as the animals made a decision and changed their minds. They published their results in Current Biology. A press release from New York University quotes co-first author on the paper Roozbeh Kiani (a former postdoctoral scholar in Newsome’s lab):

“Looking at one neuron at a time is ‘noisy’: results vary from trial to trial so you cannot get a clear picture of this complex activity. By recording multiple neurons at the same time, you can take out this noise and get a more robust picture of the underlying dynamics.”

The team was able to watch the neurons firing in real time, and detect a pattern indicating which decision the animal was going to make. They could also tell when the animal changed its mind, for example as a result of a stronger signal on the screen or to more time to make a decision. What I found interesting is that in most cases when the animals changed their minds it was to correct their initial decision.

What does all this suggest about my donut splurge? Maybe that given enough time I was able to correct my initial decision of self-control to the right one – of deliciousness.

Previously: Co-leader of Obama’s BRAIN Initiative to direct Stanford’s interdisciplinary neuroscience institute

Medical Education, Science, Stanford News

Bio-X Kids Science Day inspires young scientists

Bio-X Kids Science Day inspires young scientists

sciencefair_2691What better way to spend a sunny Friday afternoon than by letting a gooey cornstarch slurry ooze between your grubby fingers.

No? Then perhaps investigating the bacteria of your nose (the outside) is more of an end of the week treat. In the case of my kids, attempting a tae kwon do sparring match with a reluctant robot was another great way to enjoy the tenth annual Stanford Bio-X Kids Science Day.

About 200 kids showed up to the Clark Center courtyard June 13 to explore 15 booths of interactive fun. In the ten years of this event, Heideh Fattaey, executive director of operations & programs for Bio-X, said that around 2,000 kids have come to learn about science and have fun – and by extension, to discover that learning about science is fun.

Other booths had an array of magnets to investigate, pools of water with a collection of toys for learning about mass and volume, and a demonstration of the 50 cent paper microscope developed by bioengineer Manu Prakash, PhD, and his lab.

Every 20 minutes or so, an explosion from air-powered, t-shirt-shooting robot interrupted the festivities (finders keepers on the t-shirt).

sciencefair_2771In the center of the courtyard, undergraduate student Tony Pratkanis stood watch over the PS2 personal robot, not far from a bubble machine that held several kids in thrall. The robot had, on another day, made an independent coffee run for the lab of computer scientist Kenneth Salisbury. On Friday the robot was set to dole out high fives, though that program met its match with my son’s kicking.

Fattaey told me that the day is intended not just to wear out active kids, but to inspire the next generation of scientists who will be picking up biomedical innovation where today’s Bio-X faculty leave off.

Case in point, Fattaey said she talked with a high school student she knew who was going to be doing a summer internship in a Clark Center lab. “He said seeing all the kids have fun brought back memories of when he attended Kids Science Day,” she said.

Previously: Stanford Medicine community gathers for Health Matters event, At Med School 101, teens learn that it’s “so cool to be a doctor”, A day in the lab: Stanford scientists share their stories, what fuels their work, Stanford’s Clark Center, home to Bio-X, turns 10 and Bay Area students get a front-row seat to practicing medicine, scientific research
Photos, of Quinn and Reid Monahan playing with a cornstarch slurry, and of Reid Monahan sparring with the PS2 personal robot, by Amy Adams

Big data, Stanford News, Technology

What computation tells us about how our bodies work

What computation tells us about how our bodies work

Last week, as the 2014 Big Data in Biomedicine conference came to a close, a related story about the importance of computing across disciplines posted on the Stanford University homepage. The article describes research making use of the new Stanford Research Computing Center, or SRCC (which we blogged about here). We’re now running excerpts from that piece about the role computation, as well as big data, plays in medical advances.

cup of coffeeAs you sip your morning cup of coffee, the caffeine makes its way to your cells, slots into a receptor site on the cells’ surface, and triggers a series of reactions that jolt you awake. A similar process takes place when Zantac provides relief for stomach ulcers, or when chemical signals produced in the brain travel cell-to-cell through your nervous system to your heart, telling it to beat.

In each of these instances, a drug or natural chemical is activating a cell’s G-protein coupled receptor (GPCR), the cellular target of roughly half of all known drugs, says Vijay Pande, PhD, a professor of chemistry and, by courtesy, of structural biology and computer science at Stanford. This exchange is a complex one, though. In order for caffeine or any other molecule to influence a cell, it must fit snuggly into the receptor site, which consists of 4,000 atoms and transforms between an active and inactive configuration. Current imaging technologies are unable to view that transformation, so Pande has been simulating it using his Folding@Home distributed computer network.

So far, Pande’s group has demonstrated a few hundred microseconds of the receptor’s transformation. Although that’s an extraordinarily long chunk of time compared to similar techniques, Pande is looking forward to accessing the SRCC to investigate the basic biophysics of GCPR and other proteins. Greater computing power, he says, will allow his team to simulate larger molecules in greater detail, simulate folding sequences for longer periods of time, and visualize multiple molecules as they interact. It might even lead to atom-level simulations of processes at the scale of an entire cell. All of this knowledge could be applied to computationally design novel drugs and therapies.

“Having more computer power can dramatically change every aspect of what we can do in my lab,” says Pande, who is also a Stanford Bio-X affiliate. “Much like having more powerful rockets could radically change NASA, access to greater computing power will let us go way beyond where we can go routinely today.

Previously: Computing our evolution, Learning how to learn to readPersonal molecular profiling detects diseases earlier, New computing center at Stanford supports big data and Nobel winner Michael Levitt’s work animates biological processes
Photo by Toshiyuki IMIA

Big data, Genetics, Stanford News, Technology

Computing our evolution

Computing our evolution

Last week, as the 2014 Big Data in Biomedicine conference came to a close, a related story about the importance of computing across disciplines posted on the Stanford University homepage. The article describes research making use of the new Stanford Research Computing Center, or SRCC (which we blogged about here). We’re now running excerpts from that piece about the role computation, as well as big data, plays in medical advances.

The human genome is essentially a gigantic data set. Deep within each person’s 6 billion data points are minute variations that tell the story of human evolution, and provide clues to how scientists can combat modern-day diseases.

To better understand the causes and consequences of these genetic variations, Jonathan Pritchard, PhD, a professor of genetics and of biology, writes computer programs that can investigate those linkages. “Genetic variation effects how cells work, both in healthy variation and in response to disease, which ultimately regulates organism-level phenotypes,” Pritchard says. “How natural selection acts on phenotypes, that’s what causes evolutionary changes.”

Consider, for example, variation in the gene that codes for lactase, an enzyme that allows mammals to digest milk. Most animals don’t express lactase after they’ve been weaned from their mother’s milk. In populations that have historically revolved around dairy farming, however, Pritchard’s algorithms have shown that there has been strong long-term selection for expressing the genes that allow people to process milk. There has been similarly strong selection on skin pigmentation in non-Africans that allow better synthesis of vitamin D in regions where people are exposed to less sunlight.

The methods used in these types of investigations have the potential to yield powerful medical insights. Studying variations in gene regulation within a population could reveal how and where particular proteins bind to DNA, or which genes are expressed in different cell types – information that could be applied to design novel therapies. These inquiries can generate hundreds of thousands of data sets, which can only be parsed with clever algorithms and machine learning.

Pritchard, who is also a Stanford Bio-X affiliate, is bracing for an even bigger explosion of data; as genome sequencing technologies become less expensive, he expects the number of individual genomes to jump by as much as a hundredfold in the next few years. “There are not a lot of problems that we’re fundamentally unable to handle with computers, but dealing with all of the data and getting results back quickly is a rate limiting step,” Pritchard says. “Having access to SRCC will make our inquiries go easier and more quickly, and we can move on faster to making the next discovery.”

Previously: Learning how to learn to readPersonal molecular profiling detects diseases earlier and New computing center at Stanford supports big data

Big data, Imaging, Stanford News, Technology

Learning how we learn to read

Learning how we learn to read

Last week, as the 2014 Big Data in Biomedicine conference came to a close, a related story about the importance of computing across disciplines posted on the Stanford University homepage. The article describes research making use of the new Stanford Research Computing Center, or SRCC (which we blogged about here). We’re now running excerpts from that piece about the role computation, as well as big data, plays in medical advances.

letter - smallA love letter, with all of its associated emotions, conveys its message with the same set of squiggly letters as a newspaper, novel, or an instruction manual. How our brains learn to interpret a series of lines and curves into language that carries meaning or imparts knowledge is something psychology professor Brian Wandell, PhD, has been trying to understand.

Wandell hopes to tease out differences between the brain scans of kids learning to read normally and those who are struggling, and use that information to find the right support for kids who need help. “As we acquire information about the outcome of different reading interventions we can go back to our database to understand whether there is some particular profile in the child that works better with intervention 1, and a second profile that works better with intervention 2,“ said Wandell, who is also the Isaac and Madeline Stein Family Professor and a professor (by courtesy) of electrical engineering.

His team developed a way of scanning kids’ brains with magnetic resonance imaging then knitting the million collected samples together with complex algorithms that reveal how the nerve fibers connect different parts of the brain. “If you try to do this on your laptop, it will take half a day or more for each child,” he said. Instead, he uses powerful computers to reveal specific brain changes as kids learn to read.

Wandell is associate director of the Stanford Neurosciences Institute where he is leading the effort to develop a computing strategy – one that involves making use of SRCC rather than including computing space in their planned new building. He said one advantage of having faculty share computing space and systems is to speed scientific progress. “Our hope for the new facility is that it gives us the chance to set the standards for a better environment for sharing computations and data, spreading knowledge rapidly through the community,” he said.

Previously: Personal molecular profiling detects diseases earlier, New computing center at Stanford supports big data, Teaching an old dog new tricks: New faster and more accurate MRI technique quantifies brain matter, Study shows brain scans could help identify dyslexia in children before they start to read and Stanford study furthers understanding of reading disorders
Photo by Liz West

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