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Infectious Disease, Research, Science, Stanford News

Science Friday-style podcast explains work toward a universal flu vaccine

Science Friday-style podcast explains work toward a universal flu vaccine

I had the pleasure of teaching a class this fall to a group of mostly chemistry and chemical engineering graduate students, helping them improve their skills communicating about their science with the public. For her assignment, graduate student Julie Fogarty recorded this Science Friday-style segment on work taking place in the lab of chemical biologist and bioengineer James Swartz, PhD. Swartz and colleagues are trying to develop a universal flu vaccine that would eliminate the need to get a new vaccine each year – something all of us would probably appreciate. (Here I’m thinking about my colleague Michelle Brandt, who recently suffered the woes of not finding time to get her kids vaccinated.)

Julie’s brother Skyped in for his role as Science Friday host extraordinaire Ira Flatow in this segment, while Julie played the enthusiastic and articulate guest. It’s often difficult to explain complex science in audio format, but Julie does a fantastic job explaining the work in way that is very visual. I love her description of the flu virus as a little mushroom.

(A previous blog entry featured another student, Rhiannon Thomas-Tran, who produced a great video about her work.)

Previously: Working to create a universal flu vaccine, Graduate student explains pain research in two-minute video and How one mom learned the importance of the flu shot – the hard way

Genetics, Neuroscience, Research, Science, Stanford News

Yeast advance understanding of Parkinson’s disease, says Stanford study

Yeast advance understanding of Parkinson's disease, says Stanford study

It’s amazing to me that the tiny, one-celled yeast can be such a powerful research tool. Now geneticist Aaron Gitler, PhD, has shown that the diminutive organism can even help advance the understanding of Parkinson’s disease and aid in identifying new genes involved in the disorder and new pathways and potential drug targets. He published his findings today in Neuron and told me in an email:

Parkinson’s disease is associated with many genetic and environmental susceptibility factors. Two of the newest Parkinson’s disease genes, EIF4G1 and VPS35, encode proteins involved in protein translation (the act of making protein from RNA messages) and protein sorting (shuttling proteins to the correct locations inside the cell), respectively. We used unbiased yeast genetic screens to unexpectedly discover a strong genetic interaction between these two genes, suggesting that the proteins they encode work together.

The proteins, EIF4G1 and VPS35, have changed very little from yeast to humans. Gitler and his colleagues showed that VPS35 interacts functionally with another protein implicated in Parkinson’s disease, alpha-synuclein, in yeast, round worms and even laboratory mice. As Gitler described:

Together, our findings connect three seemingly distinct Parkinson’s disease genes and provide a path forward for understanding how these genes might contribute to the disease and for identifying therapeutic interventions. More generally, our approach underscores the power of simple model systems for interrogating even complex human diseases.

Previously: Researchers pinpoint genetic suspects in ALS and In Stanford/Gladstone study, yeast genetics further ALS research

Patient Care, Public Health, Research, Science

Finding cures for the most challenging diseases

640px-Drawing_Test_tubes_different_colorsThe recent Ebola outbreak and the subsequent race to find a vaccine and other treatment options has brought the topic of drug development back in the public spotlight. But despite the millions of dollars spent on these efforts and the technological advances in biomedical sciences in the last 20 years or so, the process is still time-consuming and prone to failure. A recent feature story from National Journal (which also appears on The Atlantic’s website today) describes the work of several scientists trying to find cures or treatments for some of the most challenging diseases, from infectious diseases, like AIDS and Ebola, to chronic diseases such as Alzheimer’s.

The first disease the article highlights is a rare disorder called progeria, which causes young children to age prematurely. Recent breakthroughs in treatment have come from a team led by Francis Collins, MD, PhD, who is more famous for leading the Human Genome Project and now serves as director for the National Institutes of Health. Collins worked briefly on progeria early in his career and the combination of Collins’s work and genomics made it possible for his team to crack the genetic secret of the rare disease: that it was caused by a single genetic mutation. That finding led to a treatment that extended the lives of patients with progeria by several years. But it also points to some of the overwhelming challenges of chasing down cures and treatments:

The doctors and scientists hunting for new cures and treatments work in a constant state of tension. They operate in a tremendously high-stakes environment, pouring years of their lives into research as the people who inspire them continue to suffer and even die. Drug hunters face failure after failure, almost never followed by success. Decades of work flame out. Promising ideas turn into dead ends. For every 10,000 compounds they explore, scientists wind up with just one drug approved by the Food and Drug Administration. Even when medical science moves as fast as it can—and today, it’s moving faster than ever before—it’s still an agonizingly slow process.

“As much as we say that failure is part of what we do—if you’re not failing, you’re probably not doing science that’s very interesting—it still hurts,” Collins says. “It is frustrating, because you want to come up with the answer. You want to save lives. That’s what we all get into this medical research area to try to achieve, and yet the challenges are immense. And we make progress, oftentimes, in very small baby steps, even though what we’re hoping for are big leaps.”

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Aging, In the News, Neuroscience, Research, Science, Stanford News

Stanford research showing young blood recharges the brains of old mice among finalists for Science Magazine’s Breakthrough of the Year

Stanford research showing young blood recharges the brains of old mice among finalists for Science Magazine's Breakthrough of the Year

ballot box

Stanford research showing that an infusion of young blood recharges the brains of old mice is one of the finalists for Science magazine’s annual contest for People’s Choice for Breakthrough of the Year. Today is the last day to cast your vote. Click here if you’d like to support the work, which could lead to new therapeutic approaches for treating dementia.

Several months ago, I had the pleasure of helping break the news about this great piece of research. So, let’s face it, I take a certain amount of pride in the amount of news coverage it received and the attention it’s getting now.

But the real credit goes to Stanford neuroscientist Tony Wyss-Coray, PhD, along with his able lead author Saul Villeda, PhD, and colleagues. This important discovery by Wyss-Coray’s team revealed that infusing young mice’s blood plasma into the bloodstream of old mice makes those old mice jump up and do the Macarena – and perform a whole lot better on mousey IQ tests.

Infusing blood plasma is hardly a new technique. As Wyss-Coray told me when I interviewed him for my release:

“This could have been done 20 years ago….You don’t need to know anything about how the brain works. You just give an old mouse young blood and see if the animal is smarter than before. It’s just that nobody did it.”

And after all, isn’t that what breakthroughs are all about? It’s still too early to say, but this simple treatment – or (more likely) drugs based on a better understanding of what factors in blood are responsible for reversing neurological decline –  could someday turn out to have applications for Alzheimer’s disease and much more.

At last count, the Wyss-Coray’s research is neck-and-neck with a competing project for first place. If you think, as I do, that a discovery with this much potential deserves a vote of confidence make sure to take a moment this afternoon to cast your virtual ballot.

Previously: The rechargeable brain: Blood plasma from young mice improves old mice’s memory and learning, Old blood makes young brains act older, and vice versa and Can we reset the aging clock, once cell at a time?
Photo by FutUndBeidl

Pain, Science, Stanford News, Videos

Graduate student explains pain research in two-minute video

Graduate student explains pain research in two-minute video

Earlier this year I wrote about some fascinating research from the lab of chemist Justin Du Bois, PhD, who has been working with naturally occurring toxins with the goal of developing ways of combatting pain. This class of toxins is found in a number of poisonous animals, including the newts scurrying around Stanford campus, puffer fish and mollusks in red tides.

Now, graduate student Rhiannon Thomas-Tran, who has been working with Du Bois, produced a great video describing their approach, complete with some pretty creative drawings.

Previously: Toxins in newts lead to new way of locating pain

Neuroscience, Podcasts, Science, Stanford News

Stanford neurobiologist Bill Newsome: Seeking gains for the brain

Stanford neurobiologist Bill Newsome: Seeking gains for the brain

14601014695_30cfe1972d_zBill Newsome, PhD, knows the brain perhaps as well as the back of his hand. The Stanford neurobiologist was vice chair of the federal BRAIN Initiative launched by President Obama, and he directs the Stanford Neurosciences Institute. From that spot, he’s just funded a first round of interdisciplinary grants to Stanford faculty that he calls “risk taking.”  The need, he told me in this just-published 1:2:1 podcast, is critical:

When biomedical research money gets tight, as it now is, the funding agencies tend to get conservative. Right now we have these talented faculty at Stanford, many of them young faculty. They’re at the most creative parts of their career.  They’re at a place where they’re thinking big and dreaming big. We wanted to create this mechanism to allow them to do that.

I asked Newsome about the greatest challenges for neuroscience in the next few years. He had one word: technology. “If we were to improve the technology… If we could read out signals from the human brain and read in signals, actually do the circuit-tuning in the human brain non-invasively, at a spatial scale on the order of a millimeter or less and with fairly rapid time, it would revolutionize neuroscience,” he said.

So paint the picture, I asked, and  look ten years out. What would you like to see as far as progress? He told me:

I would like to see fundamental, substantive change on at least one devastating neurological or psychiatric disease. I don’t really care which one. Give me Alzheimer’s. Give me autism. Give me depression. Give me Parkinson’s disease. At the end of 10 years, if we can really have a breakthrough in the understanding of what causes one of those diseases mechanistically and have a therapy that dramatically improves people’s lives… I would say, ‘It’s worth it. We’ve done our job.’

Any worries or words of caution? He laments the current state of federal funding for science and worries that fiscal constraints will squeeze out young star scientists. “How do you keep convincing talented people to come into the field?” he said. “We’re deprioritizing science… How do we convince our brightest, our best, that this is a field with a really bright future?”

Previously: Deciphering “three pounds of goo” with Stanford neurobiologist Bill Newsome, Neuroscientists dream big, come up with ideas for prosthetics, mental health, stroke and more, BRAIN Initiative and the Human Brain Project: Aiming to understand how the brain works, Brain’s gain: Stanford neuroscientist discusses two major new initiatives and Co-leader of Obama’s BRAIN Initiative to direct Stanford’s interdisciplinary neuroscience institute
Photo by Allan Ajifo

History, Neuroscience, Research, Science, Stanford News

Illustration from 1881 resolves century-old brain controversy

Illustration from 1881 resolves century-old brain controversy

Figure2_WernickeThese days, a person can get through graduate school in the sciences practically without touching a physical publication. Most journals are available online going back decades. So it was a bit unusual when graduate student Jason Yeatman and postdoctoral scholar Kevin Weiner found themselves in the basement of Lane Medical Library trying to get to the bottom of a medical mystery.

It all started when Yeatman found a nerve pathway in brain images he’d taken as part of his work studying brain changes as kids learn to read.  This pathway didn’t appear anywhere in the available literature. He and Weiner became curious how this pathway – which clearly showed up in their work – could have escaped the notice of previous neuroscientists.

Their curiosity eventually led them back to an 1881 publication, still available in the basement of Lane Medical Library, where Carl Wernicke, MD, described identifying this brain pathway. Weier said, “That was a really cool experience that most people don’t have anymore, when you have to check your belongings at the door because the book you are about to look at is worth thousands of dollars per page. You are literally smelling 100 year-old ink as you find the images you have been searching for.”

Wernicke’s discovery contradicted theories by the eminent neuroanatomist at the time, Theodor Meynert, MD. I describe the controversy that led to this pathway expulsion from the literature in this Stanford News story:

Meynert strongly believed that all of the brain’s association pathways run from front to back – horizontal. This pathway, which Wernicke had called the vertical occipital fasciculus, or VOF, ran vertically. Although Yeatman and Weiner found references to the VOF under a variety of different names in texts published for about 30 years after Wernicke’s original discovery, Meynert never accepted the VOF and references to it became contentious before eventually disappearing entirely from the literature.

The group, whose work was published this week in the Proceedings of the National Academy of Sciences, says this was all more than just an exercise in curiosity. Psychologist Brian Wandell, PhD, in whose lab Yeatman was working, says it also shows the value of modern publishing methods, where making data available means scientists worldwide can try to reproduce results. He says it’s now less likely that a dispute could lead to a discovery being lost to history.

Image courtesy of PNAS

Genetics, NIH, Research, Science, Stanford News, Technology

Of mice and men: Stanford researchers compare mammals' genomes to aid human clinical research

Of mice and men: Stanford researchers compare mammals' genomes to aid human clinical research

Scientists have long considered the laboratory mouse one of the best stand-ins for researching human disease because of the animals’ genetic similarity to humans. Now Stanford researchers, as part of a consortium of more than 30 institutions, have confirmed the mouse’s utility in clinical research by showing that the basic principles controlling genes are similar between the two species. However, they also found some important differences.

From our press release on the work:

“At the end of the day, a lot of the genes are identical between a mouse and a human, but we would argue how they’re regulated is quite different,” said Michael Snyder, PhD, professor and chair of genetics at Stanford. “We are interested in what makes a mouse a mouse and a human a human.”

The research effort, Mouse ENCODE, complements a project called the Encyclopedia of DNA Elements, or ENCODE, both funded by the National Human Genome Research Institute. ENCODE studied specific components in the human genome that guide genes to code for proteins that carry out a cell’s function, a process known as gene expression. Surrounding the protein-coding genes are noncoding regulatory elements, molecules that regulate gene expression by attaching proteins, called transcription factors, to specific regions of DNA.

The Mouse ENCODE consortium annotated the regulatory elements of the mouse genome to make comparisons between the two species. Because many clinical studies and drug discovery use mice as model organisms, understanding the similarities and differences in gene regulation can help researchers understand whether their mouse study applies to humans.

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Big data, Cardiovascular Medicine, Chronic Disease, Research, Science, Stanford News, Videos

Big data approach identifies new stent drug that could help prevent heart attacks

Big data approach identifies new stent drug that could help prevent heart attacks

Ziad Ali, MD, PhD, was a cardiovascular fellow at Stanford with a rather unique skill when a 6-year study published today online in The Journal of Clinical Investigation first began.

The multi-talented physician-scientist – who is now associate director of translational medicine at Columbia University Medical Center – had figured out a way to put tiny little stents into mice with clogged arteries as a PhD student.

The skill would become key as he and colleagues set out to find a better pharmaceutical for the drug-eluting stents that are used in combination with angioplasty to treat coronary artery disease. In order to prevent stent disease, the often serious medical problem caused by stents themselves, chemotherapy drugs were added to bare metal stents. But these drug-eluting stents have their own problems: The drugs work like “hitting a pin with a sledgehemmer,” as Ali describes it, often damaging the lining of the arteries which can lead to heart attacks. As a result, patients are required to take blood thinners for up to a year after the procedure to prevent clots.

“A lot of our patient population is on the elderly side with bad hips or diabetes,” Ali told me. “Once you get a drug-coated stent, you can’t have surgery for a year. And if you stop the blood thinners for any reason, you’re at risk of a stent clotting off. And that actually causes a heart attack. Stent thrombosis has a high mortality rate.”

By using a “big data” computational approach, learning about the genetic pathways involved in coronary artery disease, then testing the new theories on mice models in the lab, researchers were able to pinpoint a potential new treatment for patients: Crizotinib, a pharmaceutical approved by the FDA for treatment in certain cases of lung cancer.

“This could have major clinical impact,” Euan Ashley, MD, PhD, senior author of the study, who discusses the work alongside Ali in the video above, said.

Previously: Euan Ashley discusses harnessing big data to drive innovation for a healthier world, New computing center at Stanford supports big data, Trial results promising for new anti-clotting drug and A call to use the “tsunami of biomedical data” to preserve life and enhance health
Photo in featured entry box by Mark Tuschman

Events, In the News, Research, Science, Stanford News

Breaking through scientific barriers: Stanford hosts 2015 Breakthrough Prize winners

Breaking through scientific barriers: Stanford hosts 2015 Breakthrough Prize winners

6018618935_38997291a8_zYoung scientists, I have good news: Nearly all of the 2015 winners of the Breakthrough Prize in Life Sciences pledged to devote at least some of their new-found riches to education programs that encourage budding scientists. No details yet, as the prizes were less than a day old when the researchers announced their plans at the Breakthrough Prize Life Sciences Symposium hosted by Stanford  yesterday.

“The Breakthrough Prize winners have done such amazing things,” said Lloyd Minor, MD, dean of the School of Medicine. Minor lauded the  founders of the award, Silicon Valley luminaries Sergey Brin and Anne Wojcicki, Jack Ma and Cathy Zhang, Yuri and Julia Milner, and Mark Zuckerberg and Priscilla Chan. “They have put together this wonderful way of rewarding and awarding scientists for the work they are doing. It’s a real privilege for us at Stanford to host the symposium.”

The six scientists, who each won a $3 million award, fielded questions and let the audience in on a secret: the path toward scientific success wasn’t always easy.

“I would have never, ever in a million years have predicted I would have been sitting up here,” said C. David Allis, PhD, a professor at The Rockefeller University who was honored for his discoveries in chromatin biology, or the study of the proteins associated with DNA. Chromatin was once thought to be useless and Allis said he received plenty of criticism about his research focus.

Jennifer Doudna, PhD, a professor of molecular and cell biology and chemistry at UC Berkeley, said she didn’t know any scientists growing up in Hawaii. It wasn’t until a cancer researcher visited her high school, giving Doudna her first glimpse at her future career. Doudna, who is also affiliated with the Howard Hughes Medical Institute and the Lawrence Berkeley National Lab, won along with microbiologist Emmanuelle Charpentier, PhD, for their work on genome editing. Charpentier leads the department of regulation in infection biology at the Helmholtz Centre for Infection Research in Germany.

Gary Ruvkun, PhD, said that although he’s a professor of genetics at Harvard Medical School and the Massachusetts General Hospital, he still hasn’t mastered the art of mentoring. “I’ve had people in my lab refer to me as the least grown up,” he said.  Ruvkun was recognized — along with molecular biologist Victor Ambros, PhD, of the University of Massachusetts Medical School — for their work on microRNAs, small pieces of RNA that regulate gene expression.

All of the winners thanked their family, mentors, colleagues, but Alim Louis Benabid, MD, PhD, thanked his patients as well. Benabid, board chairman of the Clinatec Institute in France, said many patients are embarrassed when their doctor asks them to take off their clothes. His patients let him stick his fingers in their brains, he joked. Benabid was honored for demonstrating that deep brain stimulation can alleviate some symptoms of Parkinson’s disease.

In the full-day symposium, several former Breakthrough Prize winners spoke, and Bay Area graduate students and postdocs hosted a poster session.

Previously: Are big-money science prizes a good thing?, Funding basic science leads to clinical discoveries, eventually and Why basic research is the venture capital of the biomedical world
Photo by Petras Gagilas

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