Life-saving predictions from the ICU

Similar to the “precogs” who predict crime in the movie Minority Report, but for sepsis, the deadly response to infection. Read more

Five hot projects at Emory in 2017

Five hot projects at Emory in 2017: CRISPR gene editing for HD, cancer immunotherapy mechanics, memory enhancement, Zika immunology, and antivirals from Read more

Shaking up thermostable proteins

Imagine a shaker table, where kids can assemble a structure out of LEGO bricks and then subject it to a simulated earthquake. Biochemists face a similar task when they are attempting to design thermostable proteins, with heat analogous to shaking. Read more

Department of Pediatrics

The unsweetened option

Pediatric hepatologist Miriam Vos is starting a new study testing the effects of a low-sugar diet in children with NAFLD (non-alcoholic fatty liver disease). The study is supported by the Nutrition Science Initiative and conducted in a partnership with UCSD/Rady Children’s Hospital, San Diego. See below for more on NUSI.

While there are no medications approved for NAFLD – a healthy diet and exercise are the standard of care – plenty of drugs are under development, as a recent article from Mitch Leslie in Science illustrates. As a reality check and benchmark, the NUSI study will address whether the low-tech intervention of altering diet can be effective.

Lab Land has delved into NAFLD and its increasing prevalence in previous posts. Plenty of correlational data shows that sugar intake is linked to NAFLD (a recent paper from the Framingham Heart Study), but Vos points out that there are no studies showing that reducing sugar is sufficient to drive improvement in the disease.

Diet is a challenge to examine in humans rigorously. In observational studies, investigators are always bumping up against the limits of memory and accurate reporting. In an interventional study with adults, it’s possible to provide them a completely defined menu for a short time in a closed environment, but that’s less practical for longer periods or with children.

The press release announcing the NUSI study says: half of the families will eat and drink what they normally do while the rest will be put on sugar-free meals and snacks, all of which will be provided for the participants and their families for eight weeks.

Miriam Vos, MD

I was curious about how this would work, especially for boys aged 11 to 16 (the participants in her study), so I asked Vos more about it for Lab Land.

“We try to provide them a diet that is otherwise similar to what the family is used to,” she says. “For example, if they’re accustomed to home-cooked meals, our team of nutritionists will work with them to find different recipes.” Read more

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HIV virions attached to cell membrane

The third winner of the Best Image contest from the Postdoctoral Research Symposium, from postdoc Joshua Strauss in electron microscopist Elizabeth Wright’s lab.

Strauss explains:

Tetherin is a host cell factor that mechanically links HIV-1 to the plasma membrane. This is the first time anyone has imaged tethered HIV-1 by cryo-electron tomography. In doing so, we were able to learn about the length and arrangement of the tethers.

Note: Tetherin also studied by Paul Spearman + colleagues.Joshua_Strauss_OPE_Image

Cryo-electron tomography is an imaging technique which enables scientists to look at biological specimens in a “native-like” (frozen hydrated) state, without the chemical fixatives or heavy metal stains typically used for conventional electron microscopy.

The 3D reconstruction was manually segmented to highlight the different viral and cellular components: HIV-1 virions (lavender), mature conical-cores (aqua blue), immature Gag lattice (pink), plasma membrane (peach), rod-like tethers (sea green).

Posted on by Quinn Eastman in Immunology Leave a comment

All about Saccharomyces boulardii

Pediatric infectious disease specialist Tracey Lamb earned recognition this week for her NIH New Innovator award. The goal of Lamb’s project is to develop a probiotic yeast as a platform for inexpensive oral vaccines.

“We have a long way to go to develop this vaccine Magliette Calcio A Poco Prezzo delivery system to the point where it is ready for testing in the clinic,” she says. “Now my lab can undertake more intensive research on this project to demonstrate that our design is effective in protecting against infection.”

Three points:

1. The probiotic yeast Lamb is planning to develop as a vaccine platform is Saccharomyces boulardii, which has been tested in clinical trials as a treatment for gastrointestinal disorders such as Clostridium dificile infection and several forms of diarrhea. It was originally isolated in the 1920s from fruit in Southeast Asia.

2. Saccharomyces boulardii is very close to standard baker’s yeast, Saccharomyces cerevisiae, and is actually considered a subspecies of S. cerevisiae. Genomic differences that http://www.magliettedacalcioit.com contribute to its probiotic properties are under investigation.

3. The New Innovator program, running since 2007, is one of the ways the National Institutes of Health seeks to reward especially creative or potentially transformative research proposals. The New Innovator awards, up to $1.5 million over five years, are meant for newly independent researchers building their careers. Lamb managed to snag Emory’s first.

Posted on by Quinn Eastman in Immunology Leave a comment

Americans cutting sugar – but it’s still not enough

In America’s battle against obesity, there is some good news. According to a study conducted by Emory researchers, Americans consumed nearly a quarter less added sugars in 2008 than they did 10 years earlier.

The study, published in the American Journal of Clinical Nutrition in July 2011, found that the consumption of added sugars, such as those found in sodas, sports drinks, juices and sweetened dairy products, decreased among all age groups over a decade. The largest decrease came in the consumption of sodas, traditionally the largest contributor to added sugar consumption, according to Jean Welsh, MPH, PhD, RN, study author and post-doctoral fellow in pediatric nutrition at Emory University School of Medicine.

“While we were hopeful this would be the case, we were surprised when our research showed such a substantial reduction in the amount of added sugar Americans are consuming,” said Welsh. “We’re hopeful this trend will continue.”

So, why the change? One of Welsh’s partners in the study, Miriam Vos, MD, MSPH, an assistant professor of pediatrics in the Emory University School of Medicine, and a physician on staff at Children’s Healthcare of Atlanta, attributes much of the shift to public education.

“Over the past decade, there has been a lot of public health awareness about obesity and nutrition, and I think people are starting to get the message about sugar,” says Vos. “We’re not trying to send a message that sugar is inherently bad. It’s more that the large amounts of sugar we consume are having negative effects on our health, including increasing our risk of obesity, diabetes and cardiovascular disease.”

The study interpreted data of 40,000 people’s diets collected by the Centers for Disease Control and Prevention (CDC) over 10 years.  From the surveys, researchers were able to calculate how much added sugar – that is sugar that is not originally part of a food – that Americans are consuming. In 1999-2000, the typical person’s daily diet included approximately 100 grams of added sugar, a number that had dropped to 77 grams by 2007 and 2008.

While the study shows that the amount of added sugar Americans are consuming is lower, it doesn’t mean the amount is low enough.

“The American Heart Association recommends that we get about five percent of our calories from added sugars,” says Vos. “In 1999 to 2000, people were consuming about 18 percent of their calories from added sugars. Over 10 years, that amount decreased to 14.5 percent of our daily calories, which is much better. But, clearly, 14.5 percent is still three times more than what is considered a healthy amount. We’re on the right track, but we still have room for improvement.”

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A milestone in treating hemophilia

Hematologist Pete Lollar has devoted his career to developing treatments for hemophilia A, which is caused by a lack of blood clotting factor VIII. Lollar is a professor of pediatrics in Emory School of Medicine and director of hemostasis research at Children’s Healthcare of Atlanta. Last week, Lollar was honored by Emory’s Office of Technology Transfer for setting in motion research that has progressed to a phase III clinical trial of a new product, OBI-1, a special form of factor VIII.

John "Pete" Lollar, MD

Along with this milestone came a dramatic story, described by OTT’s assistant director Cale Lennon. The first patient to enroll in the clinical trial did so in November 2010 because of what appeared to be acquired hemophilia, which led to severe uncontrolled hemorrhaging. As a result of treatment with OBI-1, developed by Lollar and his research team at Emory, the patient’s bleeding was brought under control and it saved his life. He was treated at Indiana Hemophilia and Thrombosis Center in Indianapolis.

Acquired hemophilia is a challenge for doctors to deal with because it is such a surprise. Unlike people with inherited hemophilia, those with acquired hemophilia do not have a personal or family history of bleeding episodes. Their immune systems are somehow provoked into making antibodies against their own clotting factor VIII. These antibodies also appear over time in about 30 percent of patients with inherited hemophilia who take standard clotting factors.

OBI-1, a special form of clotting factor VIII, is less of a red flag to the immune system. This allows treatment of patients who cannot benefit from standard clotting factor VIII, because of the presence of auto-antibodies.

Emory originally licensed OBI-1 to Octagen Corporation, a “homegrown” startup company founded in 1997. Octagen sublicensed the OBI-1 technology to a French biotechnology firm, Ipsen Biopharm in 1998. Over the next decade, Octagen and Ipsen pursued preclinical and initial clinical studies and completed a phase II clinical trial in 2006. Ipsen purchased the OBI-1 program outright in May 2008.

In January 2010, Ipsen developed a partnership agreement with Inspiration Biopharmaceuticals, which was founded by two businessmen whose children have hemophilia. Under the agreement’s terms, Inspiration licensed OBI-1 from Ipsen and is responsible for its clinical development, regulatory approval and commercialization.

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