Researchers find new gene interaction associated with increased MS risk 03-28

A person carrying variants of two particular genes could be almost three times more likely to develop multiple sclerosis, according to the latest findings from scientists at The University of Texas Medical Branch at Galveston and Duke University Medical Center.

One of these variants is in IL7R, a gene previously associated with MS, and the other in DDX39B, a gene not previously connected to the disease.

The discovery could open the way to the development of more accurate tests to identify those at greatest risk of MS, and possibly other autoimmune disorders, the researchers said.

The findings are published in the latest issue of Cell.

A disease in which the body’s own immune system attacks nerve cells in the spinal cord and brain, MS is a major cause of neurological disease in younger adults, from 20 to 50 years of age, and disproportionally affects women. While treatable, there is no cure for MS, which can lead to problems with vision, muscle control, balance, basic body functions, among other symptoms, and could lead to disability.

Available treatments have adverse side effects as they focus on slowing the progression of the disease through suppression of the immune system.

Thanks to the collaboration between scientists at UTMB, Duke, University of California, Berkeley, and Case Western Reserve University, researchers found that when two particular DNA variants in the DDX39B and IL7R genes are present in a person’s genetic code, their interaction can lead to an over production of a protein, sIL7R. That protein’s interactions with the body’s immune system plays an important, but not completely understood, role in MS.

“Our study identifies an interaction with a known MS risk gene to unlock a new MS candidate gene, and in doing so, open up a novel mechanism that is associated with the risk of multiple sclerosis and other autoimmune diseases,” said Simon Gregory, director of Genomics and Epigenetics at the Duke Molecular Physiology Institute at Duke University Medical Center and co-lead author of the paper in Cell.

This new information has potentially important applications.

“We can use this information at hand to craft tests that could allow earlier and more accurate diagnoses of multiple sclerosis, and uncover new avenues to expand the therapeutic toolkit to fight MS, and perhaps other autoimmune disorders,” said Gaddiel Galarza-Muñoz, first author on the study and postdoctoral fellow at UTMB.

It can sometimes take years before an MS patient is properly diagnosed allowing the diseases to progress and resulting in further damage to the nervous system before treatment begins.

With more accurate measures of risk, health care providers would be able to screen individuals with family histories of MS or with other suspicious symptoms. It could lead those with certain genotypes to be more vigilant.

“One could envision how this type of knowledge will someday lead to diagnose multiple sclerosis sooner and, now that we have promising therapies, a doctor could start the appropriate treatment more quickly. It is not out the realm of possibility to imagine a path for screening for other autoimmune diseases such as Type 1 Diabetes,” said Dr. Mariano Garcia-Blanco, Professor and Chair of the department of biochemistry and molecular biology at UTMB, and co-lead author of the paper.

For Garcia-Blanco the fight against MS is personal. He was already working on research related to MS when in 2012 he found out his daughter, then in her late 20s, had been diagnosed with the disease. Garcia-Blanco said this refocused his efforts on his MS related work.

“I’m much more aware now of how the work we do in the lab could someday lead to something that can be used to help those who have to live with MS”, Garcia-Blanco said.

Other study authors include Farren B.S. Briggs, Irina Evsyukova, Geraldine Schott-Lerner, Edward M. Kennedy, Tinashe Nyanhete, Liuyang Wang, Laura Bergamaschi, Steven G. Widen, Georgia D. Tomaras, Dennis C. Ko, Shelton S. Bradrick and Lisa F. Barcellos.

The research was supported by the National Institutes of Health, National MS Society Pilot Award, Duke University Whitehead Scholarship, Ruth and A. Morris Williams Faculty Research Prize funds from Duke University School of Medicine, start-up funds from UTMB and funds from Mr. Herman Stone and family for MS research.

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A Chip That Mimics Human Organs Is the Design of the Year 07-06

A Chip That Mimics Human Organs Is the Design of the Year

 Paola Antonelli, the senior curator of design and architecture at the Museum of Modern Art, added an intriguing object to the museum’s permanent collection. It was a clear plastic chip, no bigger than a thumb drive, and it could soon change the way scientists develop and test life-saving medicines.

Called Organs-On-Chips, it’s exactly what it sounds like: A microchip embedded with hollow microfluidic tubes that are lined with human cells, through which air, nutrients, blood and infection-causing bacteria could be pumped. These chips get manufactured the same way companies like Intel make the brains of a computer. But instead of moving electrons through silicon, these chips push minute quantities of chemicals past cells from lungs, intestines, livers, kidneys and hearts. 

Networks of almost unimaginably tiny tubes give the technology its name—microfluidics—and let the chips mimic the structure and function of complete organs, making them an excellent testbed for pharmaceuticals. The ultimate goal is to lessen dependence on animal test subjects and decrease time and cost for developing drugs. Last year, researchers from Harvard’s Wyss Institute for Biologically Inspired Engineering started a company called Emulate, which is now working with companies like Johnson & Johnson on just this idea: pre-clinical trial testing. The company is currently working on incorporating Emulate’s chips into its research and development programs.

When the Harvard team first published its findings on the chips in 2010, the research was purely scientific. Now, five years later, it’s not only been inducted into the world’s foremost design collection, it’s also been named Design of the Year.very year, London’s Design Museum names one project as the year’s best. Past winners have included Zaha Hadid’s ethically-questionable (but stunning) Heydar Aliyev Cultural Centre in Azerbaijan, a lightbulb, and a government website. That a piece of medical equipment developed by biological engineers is this year’s winner isn’t just a nod to the design’s worthiness. It also says something about how views of what counts as “design” are changing.

To be sure, Organs-On-Chips is aesthetically brilliant. Antonelli, who recently called synthetic biology the most exciting frontier in design, described the chips as the epitome of design innovation. “In some lucky cases, the form is striking,” she says, referring to objects born out of scientific research. “In this particular case, added bonus, not only is the form striking, but so is the function—the idea behind the object.” Like a biological system, the chip’s form dictates its function, and its form is undeniably beautiful. But that’s not the end of the story. “Most people say form follows function, but it’s exactly the opposite in biology,” says Donald Ingber, a bioengineer and founding director of the Wyss Institute, which developed the chip and is working on commercializing it. 

“Actually, that’s not fair. It’s a dynamic relationship.” The structure of a biological system will inevitably affect the way it works, but Ingber says the design principle works both ways. “If you change the function, you can actually modulate the structure,” he says, noting how the diameter of blood vessels will adapt to decrease the tension in people who develop hypertension.

Working on the microscale requires precision. The chip effectively replaces the three-dimensional structures of an organ—the renal tubules of a kidney, the alveoli of the lungs, the veins in a liver—with tissue-lined microfluidic channels. Then it emulates the mechanics of those structures. For example, running air through a channel while using a vacuum to introduce a flexing motion will simulate the patterns of human breathing. The chip’s translucent polymer, in which the channels are encased, allows scientists to see what’s happening inside organs on the microscale. The prototypes can also be linked together to form a whole-body network of organs.

Organs-On-Chips embraces the most basic of design principles: efficiency. “Design in its greatest simplicity is minimizing any system down to its elements so as to have the greatest impact,” says Ingber. Like an increasing number of researchers, he understands that good science requires an understanding of good design. The principles that govern the two fields aren’t totally separate—in fact, design is a thread that runs through every field. It’s heartening when a big award reminds us of that.

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Single-cell breakthroughs let scientists see exactly what we’re all made of 07-05

Single-cell breakthroughs let scientists see exactly what we’re all made of

In Israel for Broad Institute conference, Eric Lander, pioneer of Human Genome Project, marvels at speed with which ‘new genomics’ opens ways to fight disease

Two years ago, when mathematician and biologist Eric Lander was in Israel for an innovative gathering of researchers and students, he took a break from his conference to describe to The Times of Israel how scientists had completed the sequencing of the human genome — a person’s “parts list” — and were now working on the “wiring diagram,” setting out how those parts work together.


Back in Israel recently for the third of his Broad Institute’s annual conferences, Lander enthused over the “amazing” pace at which science has moved on since that last visit, most especially in the study of single cells — what he called “the new genomics.”


One of the founding fathers of the Human Genome Project, Lander has dedicated his work to understanding what makes us tick, the better to keep us ticking. To underline the significance of this work for all of us, I headlined my 2013 interview with him, “This man’s work will change your life.” What’s unfolded in the last two years, he said, is a growing ability to identify what we humans are made of at the most fundamental level — the level of a single cell — with extraordinary potential benefits for understanding, observing and treating the diseases that afflict us.

Lander, 58, is the founding director of the Broad Institute of Harvard and MIT, which is devoted to utilizing human genome research in medicine. He was back in Israel for the “Third Annual Broad-Israel Science Foundation (ISF) Cell Circuits Symposium” — which brought together experts and students from the Broad Institute, from Harvard, and from Israel’s universities, on the cutting edge of human genome research and its applications for medicine.

Capitalizing on an Israeli scientific community that is very strong when it comes to combining biology and info-technology skills, the Broad-Israel partnership encourages Israeli and American trailblazing in an increasing number of joint projects, all designed to speed our progress toward thwarting cancers, Alzheimer’s, diabetes and other diseases.

Explaining the rapid advances in single-cell research, Lander said that as recently as two years ago, scientists had only what you might consider “a pixelated, low-resolution image” of our cell structure. They really didn’t know how many different types of cells there are in the body, and they couldn’t identify the differences between them.

“In the past we had a kind of blended big picture, a ‘smoothie,'” said Lander, finding another metaphor to enlighten this non-expert. “Now, because of new laboratory techniques and maths and advances in DNA sequencing,” he went on, “we have the ability to study single cells. Folks spent 40 years working to identify the cells of the retina, the back of an eye,” he said by way of an example. “Now you can do that in an afternoon.”

And why should we care? Because, Lander positively sparkled, “the ability to do single-cell analysis, to get the identities and states of each of the cells, is the final revolution in this field. It’s the equivalent of an amazing new microscope” — a microscope that offers remarkable potential for improving our health.

Human cancer cells with nuclei (specifically the DNA) stained blue. The central and rightmost cell are in interphase, so the entire nuclei are labeled. The cell on the left is going through mitosis and its DNA has condensed.  (TenOfAllTrades/Wikipedia)
Human cancer cells with nuclei (specifically the DNA) stained blue. The central and rightmost cell are in interphase, so the entire nuclei are labeled. The cell on the left is going through mitosis and its DNA has condensed. (TenOfAllTrades/Wikipedia)

For instance? In the old days — that is, until a couple of years ago — scientists struggled to understand what constituted a tumor. What common genetic features do tumors have? How might tumors be tackled most effectively? “Now we can see the commonality, the types of cells, the proportions, the logic,” he said. “This has major implications for our health.

“You want to kill a tumor? Well, maybe our treatments work on one type of cell. We were blind to that. Now we can test a treatment on the few different types of cells.”

The new microscope, in other words, enables an unprecedentedly precise understanding of disease. “It tells us what we need to solve.”

‘The ability to do single cell analysis, to get the identities and states of each of the cells, is the final revolution in this field. It’s the equivalent of an amazing new microscope’

“Imagine medicine before gross anatomy,” Lander suggested, as he sought to put the dramatic recent progress into historical perspective. “Then comes anatomy, and you can describe the organs of the body. You can see something problematic, say, in the lung, or in the heart. Well, this is the ultimate anatomy. It will penetrate every type of medicine. Not bad for two years. This just didn’t exist last time we spoke.”

Another area of rapid progress cited by Lander is the ability to “precisely edit” the genome of human cells, which has massive potential to help treat certain diseases. Just two years ago, Feng Zhang, a researcher at the Broad, invented this power gene-editing technology by harnessing by harnessing — called CRISPR-Cas9 — that can cut genomes in any place and thus enable editing.

Already an Israeli researcher at Broad has published a paper “editing” each of the 20,000 genes to find those that are essential to particular types of cancer cells – in effect, identifying the Achilles Heels of these cancers.

These advances also might open up possibilities of altering the human gene pool, of working to create less-diseased humans, even super-humans. “There’s talk of editing the DNA of embryos to alter our gene pool,” he acknowledged. “It’s being discussed.”

Then he added dryly, “I’m not sure it’s a good idea. Eugenics hasn’t worked out too well for society. Moreover, changing DNA for one purpose can have unexpected bad consequences.”

Where the advances are clearly positive is in the capacity — as genetic mapping becomes more affordable and more sophisticated — to identify the genes that predispose to Alzheimer’s, early onset cancer and many other diseases. (A personal genome map now costs about $3,000, he said.)

In some cases, genetic information can be important to parents. “Today, doctors can check two folks getting married for some mutations that would cause a disease if it was inherited by their children. In the future you would do checks for more.”

The partnership between Broad and Israel, Lander stressed, works particularly well because of Israel’s strong information technology and bio-science communities. “Israel is such an intersection of those skill sets,” he said.

And Israel’s ever-strained public health system, he added, actually has very good electronic medical records — “a 20-year history,” he said — which makes it well-placed to utilize new advances as they become available. “In the next decade we’ll collect a lot of information, and we’ll figure out the best uses. We’ll assess the risks of disease, the possibility to intervene.”


For all of that, you need groundbreaking scientists and good data. Like the United States, said Lander, Israel has both.

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