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Genetics, In the News, NIH, Science, Technology

The quest to unravel complex DNA structures gets a boost from new technology and NIH funding

The quest to unravel complex DNA structures gets a boost from new technology and NIH funding

5232013153_7808b471a2_zIf you’ve ever tried folding a map, packing an overnight bag or coiling a string of holiday lights, you know that the way you arrange an object affects how much space it takes up and how easy it is to use in the future. This same principle is true of DNA.

As a recent article in Science News explains, the way a DNA double helix is folded, packed and coiled is known to have a big effect on how much space it requires and how easy it is to access the information stored within. But, until recently, researchers lacked the technology to fully explore these four-dimensional DNA structures.

Now, new technology and last year’s launch of the National Institutes of Health‘s five-year, $120 million, 4D Nucleome project is helping researchers reveal the complex architecture of DNA. William Greenleaf, PhD, assistant professor of genetics at Stanford, discusses the significance of a genome‘s arrangement in the Science News article:

Like the genetic text within it, the genome’s shape holds specific instructions. “The way it’s compacted forms this sort of physical memory of what the cell should be doing,” Greenleaf says.

Loops of DNA that aren’t needed by a particular cell are tucked away from the biological machinery that reads genetic blueprints, leaving only relevant genes accessible to produce proteins. Studies have shown that sections of the genome that are shoved toward the edges of a nucleus are often read less than centrally located DNA. Such specialized arrangements allow cells as diverse as brain cells, skin cells and immune cells to perform different jobs, even though each contains the same genome. “In different cell types, there are very large changes to the regions that are being used,” Greenleaf says.

Much more remains to be understood about how a genome’s shape directs its activity. Future maps might zero in on functionally interesting regions of the genome, Greenleaf says. But he cautions there is also a benefit to unbiased, general exploration. Focusing on one location in the nucleome might lead researchers to miss important structural information elsewhere, he says.

Previously: DNA origami: How our genomes foldPacked and ready to go: The link between DNA folding and disease and DNA architecture fascinates Stanford researcher – and dictates biological outcomes
Photo by: Kate Ter Haar

Bioengineering, Research, Stanford News, Technology

New Stanford-developed technology bypasses “virtual reality sickness”

New Stanford-developed technology bypasses "virtual reality sickness"

headset_newsResearchers in the Stanford Computational Imaging Group have developed a new virtual reality headset that takes into account how the human eye focuses and processes depth.

Current display technologies are essentially two-dimensional and don’t present images the way our eyes were designed to see them, which can cause “virtual reality sickness,” or VR sickness for short, after only a few minutes.

The new system involves two transparent LCD displays with a spacer in between, which is called “light field technology.” A Stanford News article describes a light field as creating “multiple, slightly different perspectives over different parts of the same pupil. The result: you can freely move your focus and experience depth in the virtual scene, just as in real life.”

Gordon Wetzstein, PhD, assistant professor of electrical engineering, developed the technology along with researchers Fu-Chung Huang and Kevin Chen. In the news piece, Wetzstein listed the variety of applications this advance could have, robotic surgery top among them: “If you have a five-hour [robotic] surgery, you really want to try to minimize the eye strain that you put on the surgeon and create as natural and comfortable a viewing experience as possible.”

But the applications aren’t limited to what has already been imagined. Wetzstein explains, “Virtual reality gives us a new way of communicating among people, of telling stories, of experiencing all kinds of things remotely or closely. It’s going to change communication between people on a fundamental level.”

You can access a short video on the new development here.

Previously: Fear factor: Using virtual reality to overcome phobias, From “abstract” to “visceral”: Virtual reality systems could help address pain, Double vision: How the brain creates a single view of the world, Discover magazine looks at super human vision and Augmented reality iOS app for color vision deficiency
Photo by Vignesh Ramachandran

Autism, Behavioral Science, Medical Apps, Nutrition, Stanford News, Technology

Stanford grad students design new tools for learning about nutrition, feelings

Stanford grad students design new tools for learning about nutrition, feelings

2789442655_1f5c33ac51_zMushrooms and tomatoes, veggies that are often reviled by preschoolers, star in a new app designed by a Stanford graduate student that aims to involve children in preparing, and eating, healthy meals.

“Children are more likely to try food that they’ve helped cook,” explained Ashley Moulton, a graduate student in the School of Education’s Learning, Design and Technology Program, in a recent Stanford News story.

Moulton’s iPad app, Nomster Chef, is one of several student projects featured in the article and accompanying video:

Before cooking, children receive an educational video about a food they’ll be working with – for example, a video on how mushrooms grow. The app also incorporates food information in the recipe steps, like the fact that tomatoes are actually a fruit.

After user-testing the app prototype, “I heard from parents that they noticed differences in how their kids are eating,” Moulton said. The app also kept kids engaged throughout the cooking process.

For her project, fellow student Karen Wang developed an iPad app called FeelingTalk that helps children with autism interpret facial expressions:

…[I]n the first level of FeelingTalk, kids choose the one face that’s different (a sad face) from the three happy faces on the screen. The app will then label the different face “sad.”

“My app will be utilizing learning mechanics that directly work with the autistic brain to help them work on something that they’re having difficulty with,” Wang said. “By leveraging something they’re good at, we’re going to teach them to get comfortable looking at people’s faces, examining the key features, and eventually understanding emotions.”

Moulton, Wang and other students will present their work this afternoon at the LDT Expo at the Stanford Graduate School of Education.

Previously: A look at the MyHeart Counts app and the potential of mobile technologies to improve human health and No bribery necessary: Children eat more vegetables when they understand how food affects their bodies
Photo by Peter Weemeeuw

Autoimmune Disease, Genetics, Immunology, Science, Stanford News, Technology

Women and men’s immune system genes operate differently, Stanford study shows

Women and men's immune system genes operate differently, Stanford study shows

A new technology for studying the human body’s vast system for toggling genes on and off reveals that genes connected with the immune system switch on and off more frequently than other genes, and those same genes operate differently in women and men. What’s more, the differences in gene activity are mostly not genetic.

A couple of years ago, geneticists Howard Chang, MD, PhD; Will Greenleaf, PhD, and others at Stanford invented a way to map the epigenome – essentially the real time on/off status of each of the 22,000 genes in our cells, along with the switches that control whether each gene is on or off.

Imagine a fancy office vending machine that can dispense 22,000 different drinks and other food items. Some selections are forever pumping out product; other choices are semi permanently unavailable. Still others dispense espresso, a double espresso or hot tea depending on which buttons you push. The activity of the 22,000 genes that make up our genomes are regulated in much the same way.

That’s a lot to keep track of. But Chang and Greenleaf’s technology, called ATAC-seq, makes it almost easy to map all that gene activity in living people as they go about their lives. Their latest study, published in Cell Systems, showed that the genes that switch on and off differently from person to person are more likely to be associated with autoimmune diseases, and also that men and women use different switches for many immune system genes. That sex-based difference in activity might explain the much higher incidence of autoimmune diseases in women — diseases like multiple sclerosis, lupus and rheumatoid arthritis.

The team took ordinary blood samples from 12 healthy volunteers and extracted immune cells called T cells. T cells are easy to isolate from a standard blood test and an important component of the immune system. With T cells in hand, the team looked at how certain genes are switched on and off, and how that pattern varied from individual to individual. Chang’s team also looked at how much change occurred from one blood draw to the next in each volunteer.

Chang told me, “We were interested in exploring the landscape of gene regulation directly from live people and look at differences. We asked, ‘How different or similar are people?’ This is different from asking if they have the same genes.”

Even in identical twins, he said, one twin could have an autoimmune disease and the other could be perfectly well. And, indeed, the team reported that over a third of the variation in gene activity was not connected to a genetic difference, suggesting a strong role for the environment. “I would say the majority of the difference is likely from a nongenetic source,” he said.

Previously: Caught in the act! Fast, cheap, high-resolution, easy way to tell which genes a cell is using
Photo by Baraka Office Support Services

Imaging, Microbiology, Research, Science, Stanford News, Technology

3-D structure of key signaling protein and receptor revealed

3-D structure of key signaling protein and receptor revealed

Using ultra-bright X-rays at SLAC National Accelerator Laboratory, a team of international researchers has captured the 3-D structure of a key signaling protein and its receptor for the first time.

The discovery provides new insight into the functioning of a common cell receptor called a G protein-coupled receptor or GPCR. Researchers estimate this protein, and its relatives, are the targets of about 40 percent of pharmaceuticals. From a SLAC release:

“This work has tremendous therapeutic implications,” said Jeffrey Benovic, PhD, a biochemist who was not involved with the study. “The study is a critical first step and provides key insight into the structural interactions in these protein complexes.”

Specifically, the researchers were able to illuminate the structure of the GPCR bonded with a signaling protein called arrestin. Arrestins and G proteins both dock with the GPCRs, however, researchers had previously only examined a bonded G protein. G proteins are generally the “on” switch, while arrestins usually signal the GPCR to turn off:

Many of the available drugs that activate or deactivate GPCRs block both G proteins and arrestins from docking.

“The new paradigm in drug discovery is that you want to find this selective pathway – how to activate either the arrestin pathway or the G-protein pathway but not both — for a better effect,” said Eric Xu, PhD, a scientist at the Van Andel Research Institute in Michigan who led the experiment. The study notes that a wide range of drugs would likely be more effective and have fewer side effects with this selective activation.

Previously: Why Stanford Nobel Prize winner Brian Kobilka is a “tour de force of science”, Funding basic science leads to clinical discoveries, eventually and Video of Brian Kobilka’s Nobel lecture
Video by SLAC National Accelerator Laboratory

Cardiovascular Medicine, Chronic Disease, Imaging, Research, Stanford News, Technology

DNA damage seen after CT scanning, study shows

DNA damage seen after CT scanning, study shows

16288548276_e155ec8843_zUsing new laboratory techniques, Stanford scientists have been able to get a closer look at what happens inside the cells of patients undergoing medical imaging techniques. In a study published today, their research clearly shows that there is cellular damage in heart patients after CT scanning.

The researchers explained to me in interviews for a press release on the study that this doesn’t link CT scans to cancer. But as Patricia Nguyen, MD, lead author said in the release, it is further indication for caution:

“Whether or not this (cellular damage) causes cancer or any negative effect to the patient is still not clear, but these results should encourage physicians toward adhering to dose reduction strategies.”

Due to an explosion in the use CT scans for heart patients over the past decade, public health concerns have been raised over whether there might be a causal link with cancer. But until now, little has been known about exactly what happens at a cellular level when patients undergo CT scanning, a type of medical imaging which exposes them to low-dose radiation. This study took advantage of new laboratory techniques that made it possible to look inside cells of patients after they underwent CT scanning. As Nguyen explained in my release:

“Because we don’t know much about the effects of low-dose radiation — all we know is about high doses from atomic bomb blast survivors — we just assume it’s directly proportional to the dose. We wanted to see what really happens at the cellular level.”

Researchers examined the blood of 67 patients undergoing cardiac CT angiography using such techniques as whole-genome sequencing and flow cytometery to measure biomarkers of DNA damage. The results:

… showed an increase in DNA damage and cell death, as well as increased expression of genes involved in cell repair and death, the study said. Although most cells damaged by the scan were repaired, a small percentage of the cells died, the study said.

“These findings raise the possibility that radiation exposure from cardiac CT angiography may cause DNA damage that can lead to mutations if damaged cells are not repaired or eliminated properly,” the study said.

Photo by frankieleon

In the News, Pediatrics, Public Health, Stanford News, Technology

Water-conscious hospital will debut in 2017 with expansion of Lucile Packard Children’s Hospital

Water-conscious hospital will debut in 2017 with expansion of Lucile Packard Children’s Hospital

hospital-expansion-exterior-stanford-childrensPlaces where people live and work tend to use a lot of water, and hospitals are no exception. According to the U.S. Environmental Protection Agency’s 2012 report on water use in public buildings, hospitals rank third in water use just behind senior care facilities and hotels.

Now, the Lucile Packard Children’s Hospital Stanford is working to buck this trend with a new expansion that will use the latest water and energy-saving techniques and tools. This 521,000 square foot addition, which will open in 2017, is predicted to use about 38 percent less water than a comparable hospital.

This sustainable approach to building design began long before the current drought situation in California made water conservation a top priority. “In 2008, when we started planning, we knew there was not enough rainfall to sustain even the most efficient hospital’s needs,” said Robin Guenther, lead designer of the expansion project, in a recent post on the Healthier, Happy Lives blog.

In the piece, Guenther and her team discuss some of the expansion’s energy saving features, including shade structures that reduce the building’s heat gain from the sun and moving the hospital’s data center to the roof where it can be cooled by a wind-powered ventilation system instead of by air conditioning. According to Guenther, these modifications will make the building’s thermal energy consumption about 60 percent less than the average hospital in Northern California.

“Sustainability is a guiding principle in everything we do,” Christopher G. Dawes, president and chief executive officer of the hospital, commented. “Everyone on our team shares in this commitment. It’s part of being a good neighbor and a member of the larger community, and ensuring we’re doing the best thing possible when it comes to preserving all of our environmental resources.”

Previously: Green roofs are not just good for the environment, they boost productivity, study shows and From the Stanford Medicine archives: A Q&A with actor Matt Damon on water and health
Image courtesy of Lucile Packard Children’s Hospital Stanford

Addiction, Mental Health, Pain, Public Health, Technology

Student engineers unveil tamper-proof pill bottle

Student engineers unveil tamper-proof pill bottle

Pill-dispenserThe United States has been battling a prescription painkiller epidemic for years. The statistics from the Centers for Disease Control and Prevention are chilling: The number of painkillers prescribed has quadrupled since 1999; more than two million people abused painkillers in 2013; every day, 44 people die from a prescription opioid overdose.

In response, faculty at the Center for Injury Research and Policy at the Johns Hopkins Bloomberg School of Public Health issued a challenge to seniors in the university’s mechanical engineering program: build a pill bottle that would protect against theft and tampering.

One team of students came up with a design that worked so well that their team’s mentors Andrea Gielen, ScD, and Kavi Bhalla, PhD, submitted a proposal to the National Institutes of Health for further testing.

The device is about the size of a can of spray paint, much larger than the average pill bottle. It can only be opened with a special key, which pharmacists can use to refill with a month’s supply of OxyContin. A fingerprint sensor ensures only the prescribed patient can access the pills at prescribed intervals and doses. In a story on the Johns Hopkins website earlier this month, Megan Carney, one of the student engineers described how the pill dispenser works:

The device starts to work when the patient scans in his or her fingerprint. This rotates a disc, which picks up a pill from a loaded cartridge and empties it into the exit channel. The pill falls down the channel and lands on a platform where the patient can see that the pill has been dispensed. The patient then tilts the device and catches the pill in their hand.

A short video about the pill dispenser shows it in action, too. The dispenser still has to undergo additional testing, but the team hopes to bring it to market soon — and help prevent future opioid overdoses.

Previously: Unmet expectations: Testifying before Congress on the opioid abuse epidemic, The problem of prescription opioids: “An extraordinarily timely topic”, Assessing the opioid overdose epidemic, Why doctors prescribe opioids to patients they know are abusing them and Stanford addiction expert: It’s often a “subtle journey” from prescription-drug use to abuse
Photo courtesy of Johns Hopkins University

Genetics, In the News, Research, Science, Stanford News, Stem Cells, Technology

CRISPR marches forward: Stanford scientists optimize use in human blood cells

CRISPR marches forward: Stanford scientists optimize use in human blood cells

The CRISPR news just keeps coming. As we’ve described here before, CRISPR is a breakthrough way of editing the genome of many organisms, including humans — a kind of biological cut-and-paste function that is already transforming scientific and clinical research. However, there are still some significant scientific hurdles that exist when attempting to use the technique in cells directly isolated from human patients (these are called primary cells) rather than human cell lines grown for long periods of time in the laboratory setting.

Now pediatric stem cell biologist Matthew Porteus, MD, PhD, and postdoctoral scholars Ayal Hendel, PhD, and Rasmus Bak, PhD, have collaborated with researchers at Santa Clara-based Agilent Research Laboratories to show that chemically modifying the guide RNAs tasked with directing the site of genome snipping significantly enhances the efficiency of editing in human primary blood cells — an advance that brings therapies for human patients closer. The research was published yesterday in Nature Biotechnology.

As Porteus, who hopes to one day use the technique to help children with genetic blood diseases like sickle cell anemia, explained to me in an email:

We have now achieved the highest rates of editing in primary human blood cells. These frequencies are now high enough to compete with the other genome editing platforms for therapeutic editing in these cell types.

Porteus and Hendel previously developed a way to identify how frequently the CRISPR system does (or does not) modify the DNA where scientists tell it. Hendel characterizes the new research as something that will allow industrial-scale manufacturing of pharmaceutical-grade CRISPR reagents. As he told me:

Our research shows that scientists can now modify the CRISPR technology to improve its activity and specificity, as well as to open new doors for its use it for imaging, biochemistry, epigenetic, and gene activation or repression studies.

Rasmus agrees, saying, “Our findings will not only benefit researchers working with primary cells, but it will also accelerate the translation of CRISPR gene editing into new therapies for patients.”

Onward!

(Those of you wanting a thorough primer on CRISPR —how it works and what could be done with it — should check out Carl Zimmer’s comprehensive article in Quanta magazine. If you prefer to learn by listening (perhaps, as I sometimes do, while on the treadmill), I found this podcast from Radiolab light, but interesting.)

Previously: Policing the editor: Stanford scientists devise way to monitor CRISPR effectiveness and “It’s not just science fiction anymore”: Childx speakers talk stem cell and gene therapy

 

Bioengineering, Cardiovascular Medicine, Global Health, Stanford News, Technology

Stanford-India Biodesign co-founder: “You can become a millionaire, but also make a difference”

Stanford-India Biodesign co-founder: "You can become a millionaire, but also make a difference"

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

4499846308_9f084d26f0_zThe three Indian biodesign fellows who were at Stanford for the past six months have returned to New Delhi, where they’ll finish up their fellowship. They’re the last class of fellows from the Stanford-India Biodesign program, and in India they’ll be joining two teams already in progress as part of the new School of International Biodesign (SIB).

Balram Bhargava, MD, executive director of Stanford-India Biodesign (India), was at Stanford for the fellow’s final presentation of their prototype. He helped establish the relationship between Stanford and India and is now revamping the new self-sufficient program.

How did Stanford-India Biodesign originate?

I was at a retirement party in September 2006 for Ulrich Sigwart, MD, who developed the first stent. He called in some friends from all over the world, including Paul Yock, MD (director of the Stanford Biodesign Program). Paul and I shared a taxi ride to Ulrich’s vacation home and got talking. That’s when the program started. By January 2008 the first batch of fellows was here.

The basic intent was to start this innovative program in India and ultimately make it self-sufficient. We selected students from India and sent them to Stanford, then they finished out their fellowship in India.

How has the program changed over the years?

Our early fellows returned from Stanford with high-end ideas such as robots. I had to pull them all down back to the ground. My role was to give this program a soul, and I think I have been successful at that. After a few years Stanford also accepted that frugal design was the right thing for the world and I’m happy about that.

Many of our students had the intention of setting up a company and becoming millionaires. We’ve given them the idea that you can become a millionaire, but at the same time you can make a difference. That’s the delicate balance we want to teach. The students have been very bright and many of them have really delivered on this dream.

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