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Applied Biotechnology, Bioengineering, Genetics, Research, Stanford News

A computer kit could lead to better way to design synthetic molecules

A computer kit could lead to better way to design synthetic molecules

SmolkeSlipping something small into cells to regulate gene expression has long been a goal of biomedical researchers. And there have been many efforts to do just that. Usually researchers concoct a teeny strip of microRNA, or miRNA, and hope it does the trick.

But now, researchers at Stanford’s Department of Bioengineering have developed a computer model to take the guesswork out of designing miRNA. The model determines how to assemble a molecule so it will measure the level of a certain compound in a cell and then use that information to regulate the expression of a gene.

The research is featured in the current edition of Nature Methods, and senior author Christina Smolke, PhD, describes the process in a release issued this week:

“You start with an idea of what you want to do in the cell, and then you build and iterate on a design over and over until you reach something close to what you want,” Smolke said. “As we design and build more sophisticated systems, we will want the ability to efficiently achieve precise quantitative behaviors, and being able to accurately predict relationships between the system inputs and outputs are important to achieving this goal.”

She and Smolke’s team — which includes former graduate student Ryan Bloom and former undergraduate Sally Winkler —tested the model on the well-known Wnt signaling pathway, which plays a key role in embryonic development, stem cell production and cancer. The synthesized miRNA correctly monitored the protein produced by the pathway, validating their model.

Becky Bach is a former park ranger who now spends her time writing about science or practicing yoga. She’s a science writing intern in the Office of Communications and Public Affairs. 

Previously: A non-surgical test for brain cancer?, From plant to pill: Bioengineers aim to produce opium-based medicines without using poppies, Researchers engineer biological “devices” to program cells
Photo of Smolke by L.A. Cicero

Behavioral Science, Evolution, Imaging, Neuroscience, Research, Stanford News, Surgery

In a human brain, knowing a face and naming it are separate worries

In a human brain, knowing a face and naming it are separate worries

Alfred E. Neuman (small)Viewed from the outside, the brain’s two hemispheres look like mirror images of one another. But they’re not. For example, two bilateral brain structures called Wernicke’s area and Broca’s area are essential to language processing in the human brain – but only the ones  in the left hemisphere (at least in the great majority of right-handers’ brains; with lefties it’s a toss-up), although both sides of the brain house those structures.

Now it looks as though that right-left division of labor in our brains applies to face perception, too.

A couple of years ago I wrote and blogged about a startling study by Stanford neuroscientists Josef Parvizi, MD, PhD, and Kalanit Grill-Spector, PhD. The researchers recorded brain activity in epileptic patients who, because their seizures were unresponsive to drug therapy, had undergone a procedure in which a small section of the skulls was removed and plastic packets containing electrodes placed at the surface of the exposed brain. This was done so that, when seizures inevitably occurred, their exact point of origination could be identified. While  patients waited for this to happen, they gave the scientists consent to perform  an experiment.

In that experiment, selective electrical stimulation of another structure in the human brain, the fusiform gyrus, instantly caused a distortion in an experimental subjects’ perception of Parvizi’s face. So much so, in fact, that the subject exclaimed, “You just turned into somebody else. Your face metamorphosed!”

Like Wernicke’s and Broca’s area, the fusiform gyrus is found on each side of the brain. In animal species with brains fairly similar to our own, such as monkeys, stimulation of either the left or right fusiform gyrus appears to induce distorted face perception.

Yet, in a new study of ten such patients, conducted by Parvizi, Grill-Spector and their colleagues and published in the Journal of Neuroscience,  face distortion occurred only when the right fusiform gyrus was stimulated. Other behavioral studies and clinical reports on patients suffering brain damage have shown a relative right-brain advantage in face recognition as well as a predominance of right-side brain lesions in patients with prosopagnosia, or face blindness.

Apparently, the left fusiform gyrus’s job description has changed in the course of our species’ evolution. Humans’ acquisition of language over evolutionary time, the Stanford investigators note, required the redirection of some brain regions’ roles toward speech processing. It seems one piece of that co-opted  real estate was the left fusiform gyrus. The scientists suggest (and other studies hint) that along with the lateralization of language processing to the brain’s left hemisphere, face-recognition sites in that hemisphere may have been reassigned to new, language-related functions that nonetheless carry a face-processing connection: for example, retrieving the name of a person whose face you’re looking at, leaving the visual perception of that face to the right hemisphere.

My own right fusiform gyrus has been doing a bang-up job all my life and continues to do so. I wish I could say the same for my left side.

Previously: Metamorphosis: At the push of a button, a familiar face becomes a strange one, Mind-reading in real life: Study shows it can be done (but they’ll have to catch you first), We’ve got your number: Exact spot in brain where numeral recognition takes place revealed and Why memory and  math don’t mix: They require opposing states of the same brain circuitry
Photo by AllenGraffiti

Applied Biotechnology, Immunology, Infectious Disease, Research, Technology

Artificial spleen shown to filter dangerous pathogens from blood

Artificial spleen shown to filter dangerous pathogens from blood

79118_webOur spleens filter out toxins from our blood and help us fight infections. But serious infections can overpower our bodies’ ability to fight them off, especially among older adults whose immune systems are weaker. Now, a research team led by Donald Ingber, MD, PhD, of Harvard has come up with an artificial “biospleen” that can trap bacteria, fungi and viruses and remove them from circulating blood. Science Magazine describes the device in a news story:

The team first needed a way to capture nasties. They coated tiny magnetic beads with fragments of a protein called mannose-binding lectin (MBL). In our bodies, MBL helps fight pathogens by latching onto them. Ingber and colleagues showed that the sticky beads could grab a variety of microbes in the test tube.

With that key challenge out of the way, the researchers were ready to design the rest of the system. They engineered a microchiplike device a little bigger than a deck of cards that works somewhat like a dialysis machine. As blood enters the device, it receives a dose of the magnetic beads, which snatch up bacteria, and then fans out into 16 channels. As the blood flows across the device, a magnet pulls the beads—and any microbes or toxins stuck to them—out of the blood, depositing them in nearby channels containing saline.

The researchers first tested their device with donated human blood tainted with bacteria. They found that filtering the blood through the device five times could eliminate 90% of the microbes.

The device improved survival rates in rats and may decrease the incidence of sepsis, a dangerous side effect of severe infections. The researchers also found that the device could filter the total volume of blood in an adult human – about 5 liters or (1.3 gallons) – in about five hours.

Previously: Our aging immune systems are still in business, but increasingly thrown out of balance
Image, of the magnetic MBL-coated nanobeads beads capturing pathogens, from Harvard University Wyss Institute

Cancer, In the News, NIH, Research, Stanford News, Women's Health

NIH Director highlights Stanford research on breast cancer surgery choices

NIH Director highlights Stanford research on breast cancer surgery choices

The director of the NIH, Francis Collins, MD, this morning weighed in on a topic that has garnered much attention lately: the type of surgery that women diagnosed with breast cancer choose. The post, found at the NIH Director’s blog, describes a recent study by Stanford researchers published earlier this month in the Journal of the American Medical Association that examined survival rates after three different types of breast cancer surgery for women diagnosed with cancer in one breast: a lumpectomy (removal of the just the affected tissue, usually followed by radiation therapy), a single mastectomy (removal of the whole affected breast), and double mastectomy (removal of the unaffected breast along with the affected one.)

In a previous post we wrote in detail about the study and the finding that the number of double mastectomies in California have increased dramatically. However, except for women with the BRCA1 or BRCA2 genes, the procedure does not appear to improve survival rates for women who undergo the surgery compared with women who choose other types of breast surgery. Collins notes:

It isn’t clear exactly what prompted this upsurge in double mastectomy, which is more expensive, risky, and prone to complications than other two surgical approaches. But [researchers] Kurian and Gomez suggest that when faced with a potentially life-threatening diagnosis of cancer in one breast—and fears about possibly developing cancer in the other—women may assume that the most aggressive surgery is the best. The researchers also said it’s also possible that new plastic surgery techniques that achieve breast symmetry through bilateral reconstruction may make double mastectomy more appealing to some women.

Despite its recent upsurge in popularity, the study found double mastectomy conferred no survival advantage over the less aggressive approach of lumpectomy followed by radiation.

Collins also points out that the slightly worse survival rates of women who undergo single mastectomies probably reflect the fact that poorer women were more likely to have this surgery and is evidence of yet another health disparity linked to economic status.

Previously: Breast cancer patients are getting more bilateral mastectomies – but not any survival benefit

Immunology, Microbiology, Public Health, Research

Gut bacteria may influence effectiveness of flu vaccine

Gut bacteria may influence effectiveness of flu vaccine

flu_shotPast research has shown that the microbes living in your gut can dictate how body fat is stored, hormone response and glucose levels in the blood, which can ultimate set the stage for obesity and diabetes. Now new research suggests that the colonies of bacteria in our intestine play an important role in your body’s response to the flu vaccine.

In the study, Emory University immunologist Bali Pulendran, PhD, and colleagues followed up on a unexpected finding in a 2011 paper: the gene that codes for a protein called toll-like receptor 5 (TLR5) was associated with strong vaccine response. Science News reports that in the latest experiment:

[Researchers] gave the flu vaccine to three different groups: mice genetically engineered to lack the gene for TLR5, germ-free mice with no microorganisms in their bodies, and mice that had spent 4 weeks drinking water laced with antibiotics to obliterate most of their microbiome.

Seven days after vaccination, all three groups showed significantly reduced concentrations of vaccine-specific antibodies in their blood—up to an eightfold reduction compared with vaccinated control mice, the group reports online … in Immunity. The reduction was less marked by day 28, as blood antibody levels appeared to rebound. But when the researchers observed the mice lacking Tlr5 on the 85th day after vaccination, their antibodies seemed to have dipped again, suggesting that without this bacterial signaling, the effects of the flu vaccine wane more quickly.

Previously: The earlier the better: Study makes vaccination recommendations for next flu pandemic, Working to create a universal flu vaccine and Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease
Photo by Queen’s University

Patient Care, Research, Technology

How can health-care providers better leverage social media to improve patient care?

How can health-care providers better leverage social media to improve patient care?

A growing number of Americans are turning to the Internet for health information and many are using social media tools to engage with patients like themselves or health-care providers. But findings recently published in the Journal of Medical Internet Research suggests that a significant portion of the health-related content on social networking sites is irrelevant or devoted to marketing or promotion of products, events and institutions. Study authors also warned that social media can quickly spread misinformation to a broad audience.

In the study, Stanford medical student Akhilesh Pathipati and colleagues analyzed Facebook search results for common medical conditions. Pathipati explains in a Sacramento Bee opinion piece how health-care providers can adopt social media strategies to address the  concerns mentioned above. He writes:

Providers should build online support systems that reach all patients. A PricewaterhouseCoopers poll found that 40 percent of respondents would use social media to cope with chronic medical conditions. If patients are embarrassed by having a stigmatized illness though, they may lack that coping mechanism.

In the short term, providers may want to set up private groups on social networking sites in which patients can interact with other affected individuals. Setting up an anonymous network may prove to be even more useful, as anonymity has been shown to help people share more about their health. The long-term goal should be to find ways to reduce the stigma associated with certain illnesses.

Previously: Lack of adoption of social media among health-policy researchers = missed opportunity, More reasons for doctors and researchers to take the social-media plunge and A reminder to young physicians that when it comes to social media, “it’s no longer about you”

Research, Sleep, Stanford News

William Dement: Stanford Medicine’s “Sandman”

William Dement: Stanford Medicine's "Sandman"

dement

Sixty years before he would be referred to as the “Father of Sleep Medicine,” William Dement, MD, PhD, got kicked out of a class for dozing off.  One of the world’s foremost sleep experts, Dement is profiled in the current issue of STANFORD magazine, with writer Nicholas Weiler describing how Dement blazed a trail for the field of sleep research and medicine.

From the piece:

When he arrived at Stanford, he set aside most of his research on dreams and shifted his focus to pathologies that affect sleep quality—and to the importance of optimal sleep in our daily lives. “It wasn’t until we realized there were sleep disorders,” he says, that people started paying attention to sleep research. In 1970, he founded the Stanford Sleep Disorders Clinic, a center dedicated to the diagnosis and treatment of these maladies. The clinic was soon inundated by patients complaining of extreme daytime sleepiness due not to narcolepsy or insomnia, but to a recently discovered disorder, sleep apnea, in which the patient’s airway would collapse during sleep, causing him to wake gasping for air hundreds of times each night.

Galvanized by the unexpected prevalence of undiagnosed sleep disorders, Dement spent the next decade working feverishly to raise the profile of sleep medicine as a clinical field. Before long, similar clinics were springing up all over the country, “and they were finding the same thing,” Dement says. Still, it wasn’t until 1993 that the first long-term epidemiological study found that 24 percent of men and 9 percent of women suffer from sleep apnea. Research at the Stanford Sleep Disorders Clinic and elsewhere has found strong correlations between sleep apnea and obesity, high blood pressure and heart disease, America’s leading cause of death.

Thanks to his work and the popular sleep class that he has taught since 1971 (more than 20,000 students have taken it!), Dement is well-respected and loved among his peers and students – something captured by this 2008 video.

Previously: Stanford docs discuss all things sleepCatching some Zzzs at the Stanford Sleep Medicine CenterThanks, Jerry: Honoring pioneering Stanford sleep research and Catching up on sleep science
Related: Stalking the netherworld of sleep and Dement keeps last class wide awake
Illustration, which originally appeared in STANFORD, by Gabriel Moreno

Autoimmune Disease, Genetics, NIH, Research, Science

Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease

Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease

I don’t know about you, but I’m fascinated with the idea of the “microbiome.” If you’re unfamiliar with the term, it describes the millions upon millions of tiny, non-human hitchhikers that live on and in you (think bacteria, viruses, fungi and other microscopic life). Although the exact composition of these molecular roommates can vary from person to person, they aren’t freeloaders. Many are vitally important to your metabolism and health.

We’ve reported here on the Human Microbiome Project, launched in 2007 and supported by the National Institutes of Health’s Common Fund. Phase 2 of the project started last fall, with grants to three groups around the country to study how the composition of a person’s microbiome might affect the onset of diseases such as type 2 diabetes and inflammatory bowel disease, as well as its role in pregnancy and preterm birth. Now the researchers, which include Stanford geneticist Michael Snyder, PhD, have published an article in Cell Host & Microbe detailing what data will be gathered and how it will be shared.

As explained in a release by the National Human Genome Research Institute:

“We’re producing an incredibly rich array of data for the community from the microbiomes and hosts in these cohorts, so that scientists can evaluate for themselves with these freely available data which properties are the most relevant for understanding the role of the microbiome in the human host,” said Lita M. Proctor, Ph.D., program director of the Human Microbiome Project at NIH’s National Human Genome Research Institute (NHGRI).

“The members of the Consortium can take advantage of each other’s expertise in dealing with some very complex science in these projects,” she said. “We’re generating these data as a community resource and we want to describe this resource in enough detail so people can anticipate the data that will be produced, where they can find it and the analyses that will come out of the Consortium’s efforts.”

As I’ve recently blogged, data-sharing among researchers and groups is particularly important for research efficiency and reproducibility. And I’m excited to hear what the project will discover. More from the release:

For years the number of microbial cells on or in each human was thought to outnumber human cells by 10 to 1. This now seems a huge understatement. Dr. Proctor noted that the 10-to-1 estimate was based only on bacterial cells, but the microbiome also includes viruses, protozoa, fungi and other forms of microscopic life. “So if you really look at the entire microbial community, you’re probably looking at more like a 100-to-1 ratio,” she said.

Although thousands of bacterial species may make their homes with human beings, each individual person is host to only about 1,000 species at a time, according to the findings of the Human Microbiome Project’s first phase in 2012.

In addition, judging from the array of common functions of bacterial genes, if the bacteria are healthy, each individual’s particular suite of species appear to come together to perform roughly the same biological functions as another healthy individual. In fact, researchers found that certain bacterial metabolic pathways were always present in healthy people, and that many of those pathways were often lost or altered in people who were ill.

Stanford’s Snyder will join forces with researchers in the laboratory of George Weinstock, PhD, of the Jackson Laboratory for Genomic Medicine in Connecticut to investigate the effect of the microbiome on  the onset of Type 2 diabetes. Snyder may be uniquely positioned to investigate the causes of the condition. In 2012, he made headlines when he performed the first ever ‘omics’ profile of himself (an analysis that involves whole genome DNA sequencing with repeated measurements of the levels of RNA, proteins and metabolites in a person’s blood over time). During the process, he learned that he was on the cusp of developing type 2 diabetes. He was able to halt the progression of the disease with changes in exercise and diet.

Previously: Stanford team awarded NIH Human Microbiome Project grantElite rugby players may have more diverse gut microbiota, study shows and Could gut bacteria play a role in mental health?

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

Biomed Bites, Research, Science, Stanford News, Videos

Studying the drivers of metastasis to combat cancer

Studying the drivers of metastasis to combat cancer

Today we’re launching Biomed Bites, a weekly series created to highlight some of Stanford Medicine’s most compelling research and introduce readers to promising scientists from across the basic and clinical sciences.

One might not think there’s much of a connection between grapes and cancer cells, but Amato Giaccia, PhD, has found some similarities. “The tumor microenvironment is very analogous to the microenvironment you would have in Napa Valley, where different types of grapes grow in different areas depending on the richness of the soil and the different climate and weather that exist,” explains the Stanford radiation oncologist and cancer biologist in the video above. “In a similar matter, tumors require different environments for them to be able to grow and… metastasize.”

Giaccia and his colleagues study the genetic and epigenetic regulators of metastasis, and their work could lead to the development of therapeutics that inhibit or eradicate the process, which contributes to 90 percent of cancer-related deaths. “Understanding the drivers of metastasis and how to best target them is going to have a major impact on cancer survival and mortality in the future,” Giaccia says.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving forward biomedical innovation here.

Previously: Cellular culprit identified for invasive bladder cancer, according to Stanford study, Potential anti-cancer therapy starves cancer cells of glucose and Nomadic cells may hold clues to cancer’s spread
Photo in featured entry box by Lee Coursey/Flickr

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