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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

Applied Biotechnology, Bioengineering, Global Health, In the News, Stanford News

Stanford bioengineer among Popular Science magazine’s “Brilliant 10”

Stanford bioengineer among Popular Science magazine’s “Brilliant 10”

prakash-popsci

Manu Prakash, PhD, a prolific inventor of low-cost scientific tools, has been named one of Popular Science magazine’s “Brilliant 10” for 2014 – an award that recognizes the nation’s brightest young minds in science and engineering.

In the last year Prakash has introduced two novel science tools made from everyday materials.

The first was a fully functional paper microscope, which costs less than a dollar in materials, that can be used for diagnosing blood-borne diseases such as malaria, African sleeping sickness and Chagas. It can also be used by children — our future scientists — to explore and learn from the microscopic world.

The second was a $5 programmable kid’s chemistry set, inspired by hand-crank music boxes. Like a music box, users crank a wheel that feeds a strip of hole-punched paper through the mechanism. When a pin hits a hole, it activates a pump that releases a precise, time-sequenced drop of a liquid onto a surface. This low-cost device can be used to test water quality, to provide affordable medical diagnostic tests, or to design chemistry experiments in schools.

The inventions are brilliant in both their elegant simplicity and their use of emerging technologies, such as 3D printers, microfluidics, laser cutters and conductive-ink printing.

“In one part of our lab we’ve been focusing on frugal science and democratizing scientific tools to get them out to people around the world who will use them,” Prakash told Amy Adams in a recent Stanford News story. “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.”

Sometimes, just for the fun of it, I’ll wander over to the Prakash lab to check out the team’s new inventions. They never fail to impress.

I heartily agree with the Popular Science editors on this year’s choices for the Brilliant 10: “Remember their names: they are already changing the world as we know it.”

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
Illustration courtesy of Popular Science magazine

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

Applied Biotechnology, Cancer, Genetics, Pediatrics, Research

Gene-sequencing rare tumors – and what it means for cancer research and treatment

Gene-sequencing rare tumors - and what it means for cancer research and treatment

Sequencing the genes of cancer patients’ tumors has the potential to surmount frustrating problems for those who work with rare cancers. Doctors who see patients with rare tumors are often unsure of which treatments will work. And, with few patients available, researchers are unable to assemble enough subjects to compare different therapies in gold-standard randomized clinical trials. But thanks to gene sequencing, that is about to change.

Though this specific research was not intended to shape the child’s treatment, similar sequencing could soon help doctors decide how to treat rare cancers in real time

That’s the take-away from a fascinating conversation about the implications of personalized tumor-gene sequencing that I had recently with two Stanford cancer experts. Cancer researcher Julien Sage, PhD, is the senior author of a recent scientific paper describing sequencing of a pediatric tumor that affects only one in every 5 million people. Alejandro Sweet-Cordero, MD, an oncologist who treats children with cancer at Lucile Packard Children’s Hospital Stanford, is leading one of Stanford’s several efforts to develop an efficient system for sequencing individual patients’ tumors.

In their paper, Sage’s team (led by medical student Lei Xu) analyzed the DNA and RNA of one child’s unusual liver tumor, a fibrolamellar hepatocellular carcinoma. The cause of this form of cancer has never been found. Curious about what genes drove the tumor’s proliferation, the scientists identified two genes that were likely culprits, both of which promoted cancer in petri dishes of cultured cells. One of the genes, encoding the enzyme protein kinase A, is a possible target for future cancer therapies.

Though this specific research was not intended to shape the child’s treatment, similar sequencing could soon help doctors decide how to treat rare cancers in real time. Sweet-Cordero is working to develop an efficient system for getting both the mechanics of sequencing and the labor-intensive analysis of the resulting genetic data completed in a few weeks, instead of the two to three months now required. “We’re trying to use this kind of technology  to really help patients,” Sage said. “If you’re dealing with a disease that may kill the patient very fast, you want to act on it as soon as possible.”

In addition to giving doctors clues about which chemotherapy drugs to try, gene sequencing gives them a new way to study tumors.

“What’s really important is that, instead of categorizing tumors based on how they look under a microscope, we’ll be able to categorize them based on their gene-mutation profile,” Sweet-Cordero said. Rather than setting up clinical trials based on a tumor’s histology, as doctors have done in the past, scientists will group patients for treatment trials on the basis of similar mutations in their tumors. “In my mind, as a clinical oncologist, this is the most transformative aspect of this technology,” he said. This is especially true for patients with rare tumors who might not otherwise benefit from clinical trials at all.

And for childhood cancers, knowing a tumor’s gene mutations could also help doctors avoid giving higher doses of toxic chemotherapy drugs than are truly needed.

“The way we’ve been successful in pediatric oncology is by being extremely aggressive,” Sweet-Cordero said. Oncologists take advantage of children’s natural resilience by giving extremely strong chemotherapy regimens, which beat back cancer but can also have damaging long-term side effects. “We end up over-treating significant groups of patients who could survive with less aggressive therapy,” Sweet-Cordero said. “If we can use genetic information to back off on really toxic therapies, we’ll have fewer pediatric cancer survivors with significant impairments.”

Meanwhile, Stanford cancer researchers are also tackling a related problem: the fact that not all malignant cells within a tumor may have the same genetic mutations, and they may not all be vulnerable to the same cancer drugs. Next month, the Stanford Cancer Institute is sponsoring a scientific symposium on the concept, known as tumor heterogeneity, and how it will affect the future of personalized cancer treatments.

Sage’s research was supported by the Lucile Packard Foundation for Children’s Health, Stanford NIH-NCATS-CTSA UL1 TR001085 and Child Health Research Institute of Stanford University. Sage and Sweet-Cordero are both members of the Stanford Cancer Institute, and the National Cancer Institute-designated Cancer Center.

Previously: Smoking gun or hit-and-run? How oncogenes make good cells go bad, Stanford researchers identify genes that cause disfiguring jaw tumor and Blood will tell: In Stanford study, tiny bits of circulating tumor DNA betray hidden cancers

Applied Biotechnology, In the News, Infectious Disease, Microbiology, Public Safety

How-to manual for making bioweapons found on captured Islamic State computer

Black DeathLast week I came across an article, in the usually somewhat staid magazine Foreign Policy, with this subhead:

Buried in a Dell computer captured in Syria are lessons for making bubonic plague bombs and missives on using weapons of mass destruction.

That got my attention. Just months ago, I’d written my own article on bioterrorism for our newspaper, Inside Stanford Medicine. So I was aware that, packaged properly, contagious one-celled pathogens can wipe out as many people as a hydrogen bomb, or more. Not only are bioweapons inexpensive (they’ve been dubbed “the poor man’s nuke”), but the raw materials that go into them – unlike those used for creating nuclear weapons – are all around us. That very ubiquity, were a bioweapon to be deployed, could make fingering the perp tough.

The focal personality in my ISM article, Stanford emergency-medicine doctor and bioterrorism expert Milana Trounce, MD, had already convinced me that producing bioweapons on the cheap – while certainly no slam-dunk – was also not farfetched. “What used to require hundreds of scientists and big labs can now be accomplished in a garage with a few experts and a relatively small amount of funding, using the know-how freely available on the internet,” she’d said.

This passage in the Foreign Policy article rendered that statement scarily apropos:

The information on the laptop makes clear that its owner is a Tunisian national named Muhammed S. who joined ISIS [which now calls itself "Islamic State"] in Syria and who studied chemistry and physics at two universities in Tunisia’s northeast. Even more disturbing is how he planned to use that education: The ISIS laptop contains a 19-page document in Arabic on how to develop biological weapons and how to weaponize the bubonic plague from infected animals.

I sent Trounce a link to the Foreign Policy article. “There’s a big difference between simply having an infectious disease agent and weaponizing it,” she responded in an email. “However, it wouldn’t be particularly difficult to get experts to help with the weaponization process. The terrorist has a picked a good infectious agent for creating a bioweapon. Plague is designated as a Category A agent along with anthrax, smallpox, tularemia, botulinum, and viral hemorrhagic fevers. The agents on the Category A list pose the highest risk to national security, because they: 1) can be easily disseminated or transmitted from person to person; 2) result in high mortality rates and have the potential for major public-health impact; 3) might cause public panic and social disruption; and 4) require special action for public-health preparedness.”

Islamic State’s interest in weaponizing bubonic plague should be taken seriously. Here’s one reason why (from my ISM article):

In 1347, the Tatars catapulted the bodies of bubonic-plague victims over the defensive walls of the Crimean Black Sea port city now called Feodosia, then a gateway to the Silk Road trade route. That effort apparently succeeded a bit too well. Some of the city’s residents escaped in sailing ships that, alas, were infested with rats. The rats carried fleas. The fleas carried Yersinia pestis, the bacterial pathogen responsible for bubonic plague. The escapees docked in various Italian ports, from which the disease spread northward over the next three years. Thus ensued the Black Death, a scourge that wiped out nearly a third of western Europe’s population.

Previously: Microbial mushroom cloud: How real is the threat of bioterrorism? (Very) and Stanford bioterrorism expert comments on new review of anthrax case
Photo by Les Haines

Applied Biotechnology, Parenting, Pediatrics, Research, Sleep, Stanford News, Technology

Biodesign fellows take on night terrors in children

Biodesign fellows take on night terrors in children

baby on bed

Standing in the Clark Center’s grand courtyard, gazing upward at scientists ascending an outdoor staircase and traversing the exterior corridors on the top two floors, one senses that big ideas take shape here. But how?

Prototyping, say Andy Rink, MD, and Varun Boriah, MS, who spent the last year as Biodesign fellows. Part of Stanford’s Bio-X community, the Biodesign Program trains researchers, clinicians and engineers to be medical-technology innovators during its year-long fellowship. Fellows learn the Biodesign Process, which could be likened to design thinking for health care. On teams of two or four, the fellows identify a substantial health-care need and generate ideas to solve it using medical-device innovation.

Though most Biodesign projects take root after fellows complete a “clinical immersion” shadowing health-care workers in a hospital to observe problems, Rink found his inspiration when visiting family and waking up to a 3-year-old relative’s screams from recurring night terrors. The problem was not so much that it affected the child – pediatricians may advise that children will likely outgrow the condition – but that it affected the parents, Rink saw.  The parent’s lost sleep and anxiety over their child’s well being had huge effects on their quality of life. (In some cases, these are so severe that Xanax and Valium may be prescribed to the children as a last-ditch effort.) What if a treatment could be found that involved no medication and no parental intervention, offering everyone a solid night’s sleep?

The physician and engineer are working with School of Medicine sleep researchers Christian Guilleminault, MD, professor of psychiatry and behavioral sciences, and Shannon Sullivan, MD, clinical assistant professor of psychiatry and behavioral sciences, on a clinical method to treat night terrors in children. In a first-floor room of the Clark Center, they’re protoyping an under-mattress device that senses how deeply a child is sleeping and is able to prevent the nightly episodes from occurring, creating a healthier sleep cycle for the children.  This relieves the parent’s anxiety, and helps the entire family sleep better.

Faculty and students from more than 40 departments across Stanford’s campus, including the schools of medicine, business, law, engineering and humanities and sciences, play a role in Biodesign, as do experts from outside the university. Fellows work closely with the Institute of Design at Stanford, attending – and then teaching – the school’s d.bootcamp. They also have access to the d.school’s facilities and consult regularly with their faculty. Some of the d.school’s methods – focusing on big problems, encouraging radical collaboration, prototyping early and user-testing before focusing on functionality – guide the trajectory of Biodesign projects.

Physicians who are Biodesign fellows often work outside their specialty, and engineers bring a mix of academic and industry experience to the design table. While faculty mentors may simply provide advice to fellows, Guilleminault and Sullivan have become invested in the course of the research as lead investigators on the study. For their involvement, they were both honored with the Biodesign Specialty Team Mentorship Award.

Fellow Boriah noted that medical-device innovation is moving from products like catheters to systems such as health IT, mobile health and software. A former CEO and co-founder of a wearable patient blood-diagnostics device, he said the Biodesign program has provided valuable “access to clinical reality.” Rink, a surgical resident at Northwestern University, said that as a fellow, he’s been “exposed to a side you don’t see in a hospital.”

The researchers are currently recruiting participants ages 2-12 for their study. Rink and Boriah are also working with the Stanford-supported StartX to see their project into the next stage of development.

Previously: Sleep, baby, sleep: Infants’ sleep difficulties could signal future problemsStudying pediatric sleep disorders an “integral part” of the future of sleep medicine and At Med School 101, teens learn that it’s “so cool to be a doctor” 
Photo by MissMayoi

Applied Biotechnology, Ophthalmology, Public Health, Stanford News, Technology

Stanford-developed eye implant could work with smartphone to improve glaucoma treatments

Stanford-developed eye implant could work with smartphone to improve glaucoma treatments

eyeGlaucoma, caused by rising fluid pressure in the eyes, is known as the silent thief of sight. Catching the disease in the early stages is critical because if detected too late it leads to blindness. Regular monitoring and controlling of the disease once detected is invaluable.

Now, Stephen Quake, PhD, professor of bioengineering at Stanford, and Yossi Mandel, MD, PhD, an applied physics and ophthalmologist at Bar-Ilan University in Israel, have developed a tiny eye implant that would allow patients to take daily or hourly measurements of eye pressure from home.

A recent Stanford Report article explains how the device works:

It consists of a small tube – one end is open to the fluids that fill the eye; the other end is capped with a small bulb filled with gas. As the [internal optic pressure] increases, intraocular fluid is pushed into the tube; the gas pushes back against this flow.

As IOP fluctuates, the meniscus – the barrier between the fluid and the gas – moves back and forth in the tube. Patients could use a custom smartphone app or a wearable technology, such as Google Glass, to snap a photo of the instrument at any time, providing a critical wealth of data that could steer treatment. For instance, in one previous study, researchers found that 24-hour IOP monitoring resulted in a change in treatment in up to 80 percent of patients.

“For me, the charm of this is the simplicity of the device. Glaucoma is a substantial issue in human health. It’s critical to catch things before they go off the rails, because once you go off, you can go blind. If patients could monitor themselves frequently, you might see an improvement in treatments,” Quake added.

The full report (subscription required) is published in the current issue of Nature Medicine.

Jen Baxter is a freelance writer and photographer. After spending eight years working for Kaiser Permanente Health plan she took a self-imposed sabbatical to travel around South East Asia and become a blogger. She enjoys writing about nutrition, meditation, and mental health, and finding personal stories that inspire people to take responsibility for their own well-being. Her website and blog can be found at www.jenbaxter.com.

Previously: What I did this summer: Stanford medical student investigates early detection methods for glaucomaTo maintain good eyesight, make healthy vision a priority and Instagram for eyes: Stanford ophthalmologists develop low-cost device to ease image sharing
Photo by Magmiretoby

Applied Biotechnology, Stanford News, Videos

Drew Endy discusses the potential to program life and future of genetic engineering at TEDxStanford

Drew Endy discusses the potential to program life and future of genetic engineering at TEDxStanford

In 2013, Drew Endy, PhD, assistant professor of bioengineering, was honored as a Champion of Change by the White House. A leader in the field of synthetic biology, Endy founded BioBricks Foundation, which has underwritten an open technical-standards-setting process for synthetic biology and developed a legal contract for making genetic materials free to share and use. He spoke at TEDxStanford about his work with designers, social scientists and others to transcend the industrialization of nature. Watch the above video to learn more about the potential for making life programmable and the future of genetic engineering.

Previously: Programming cells for chemical production and disease detection, The “new frontier” of synthetic biology, Drew Endy discusses developing rewritable digital data storage in DNA and Researchers create rewritable digital storage in DNA

Applied Biotechnology, Bioengineering, Science, Stanford News, Technology

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

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

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

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

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

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

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

Applied Biotechnology, Bioengineering, Science, Stanford News, Technology

Dr. Prakash goes to Washington

Dr. Prakash goes to Washington

Prakash at White House

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

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

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

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