Update on SIV remission studies

Recently presented insights on how an antibody used to treat intestinal diseases can suppress Read more

Granulins treasure not trash - potential FTD treatment strategy

Granulins are of interest to neuroscientists because mutations in the granulin gene cause frontotemporal dementia (FTD). However, the functions of granulins were previously Read more

Blood vessels and cardiac muscle cells off the shelf

How to steer induced pluripotent stem cells into becoming endothelial cells, which line blood Read more

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IMSD program nurtures young scientists

Guest post from Megan McCall, who works at Winship Cancer Institute. Thanks Megan!

On a Thursday afternoon this past semester, a diverse group of 50 students were listening to a lecture on the art of storytelling by Eladio Abreu, a lecturer in the Biology department. This was an unusual topic for these students, but they sat enrapt, not distracted by cell phones or laptops.

Eladio Abreu, PhD

The weekly seminar was part of the Emory Initiative to Maximize Student Development (IMSD) program, aimed at the professional development of undergraduate and graduate students in STEM fields. What sets this program apart is its commitment to increase diversity in the biological, biomedical and behavioral sciences by nurturing students who may be underrepresented in these fields. IMSD’s associate director Amanda James says the program includes some of Emory’s strongest students.

The two-year, NIH-funded research program has three main goals: preparing undergraduate students for doctoral programs in STEM fields, nurturing graduate students during their matriculation into Emory’s Ph.D. programs and increasing diversity through mentoring. They accomplish these goals by connecting undergraduates and graduates through mentorship, seminars, and career coaching, says Keith Wilkinson, IMSD director and vice-chair of the Department of Biochemistry.

(from left) Lina Jowhar, Max Cornely, Chayla Vazquez, and Jamie Guillen at an Initiative to Maximize Student development meeting.

This meeting included updates from students on their summer research plans. Answers ranged from epidemiology research with a children’s hospital in Philadelphia, to influenza research at Johns Hopkins. In addition to weekly seminars, IMSD offers classes aimed at increasing success post-graduation, workshops for career development, and pathways to funded research, a rare commodity for undergraduates. Students who can’t do funded research may use resources that IMSD offers to find other opportunities.

Lina Jowhar is an undergraduate who started the program in her third year at Emory. She is engaged in research on cystic fibrosis, a genetic disorder of the lungs, and she values the weekly meetings, particularly Abreu’s lecture on the art of storytelling. “I love his interactive teaching style,” she says. “He was comfortable letting us know that he changed the examples in his PowerPoint to include Biggie and Tupac which showed me how important it is to connect with your audience.” Read more

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NGLY1 update

Emory Medicine readers may remember the Stinchcombs, a Georgia family caring for two daughters with a genetic neurological/developmental disorder called NGLY1 deficiency. We found their efforts to care for their daughters inspiring.

The rapid discovery of several children with NGLY1 deficiency, facilitated by social media, has led to a wave of research. Two recent papers represent advances toward finding treatments.

In PLOS Genetics, Japanese scientists showed that deleting the ENGase gene can partially rescue problems created by NGLY1 deficiency in a mouse model (RIKEN press release). That implies drugs that inhibit the ENGase enzyme might have similar positive effects.

Scientists knew that the NGLY1 enzyme removes chains of sugars from misfolded proteins that are stalled in cells’ production pipeline. ENGase is another enzyme that acts on those sugar chains, and its absence compensates for the lack of NGLY1. Read more

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March for Science ATL: photos

Emory scientists and supporters of science were out in substantial numbers Saturday at the March for Science Atlanta in Candler Park.

March organizers, many of whom came from the Emory research community, say they want to continue their advocacy momentum and community-building after the event’s success. Check out the web site “Science Marches On” for post-march activities. The organizers have estimated that somewhere around 8,000 people participated in Saturday’s march, based on aerial drone footage and Atlanta Police estimates.

Marchers Jarred Whitlock, Bethany Whitlock, Erica Werner, Victor Faundez, and Chelsea Lee (left to right)

Several issues propelled the Marches for Science around the world: proposed research funding reductions, skepticism on specific issues such as climate change or vaccines, and attention on diversity in science. Some Emory folks such as autism geneticist/communicator Chris Gunter and oncology nursing leader Deborah Bruner were in Washington DC for the March for Science there.

Here in Atlanta, marchers had a variety of colorful costumes and signs, with messages ranging from the blunt to the subtle.  The crowds enjoyed sunny weather and pre-march entertainment from the punk rock band Leucine Zipper and the Zinc Fingers.

Former Emory neuroscience postdoc Alison Bernstein, who blogs as “Mommy PhD” and is now an assistant professor at Michigan State, was one of the first speakers, describing how some vaccine skeptics have embraced unproven and possibly dangerous treatments for conditions such as eczema.

Emory virologist Anice Lowen was quoted in this WABE story.

Read more

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How race + TBI experience affect views of informed consent

The upcoming HBO movie of The Immortal Life of Henrietta Lacks reminds us that biomedical research has a complex legacy, when it comes to informed consent and people of color.

A paper from Emory investigators, published in AJOB Empirical Bioethicstouches on related current issues. The paper examines how race and close experience with traumatic brain injury affect study participants’ views of informed consent in clinical research.

This emerged from a study of community consultation for EFIC (exception from informed consent), in connection with a nationwide clinical trial of progesterone for traumatic brain injury (TBI). EFIC describes clinical research performed when the normal process of obtaining patients’ informed consent is not possible, because of emergency conditions such as seizures or TBI. Before such studies can be undertaken, the FDA calls for protective procedures and community consultation.

In this case, researchers surveyed 2612 people at 12 sites involved in the TBI study. The survey asked about attitudes toward the EFIC aspects of the study and also asked if they had personal experience with traumatic brain injury – either themselves or someone close to them. How that personal connection affected their responses was influenced by race.

Key paragraph from discussion:

Among white participants, increased levels of acceptance of EFIC were found among those with any connections to TBI. On the other hand, among participants identifying as black or other nonwhite races, there was decreased acceptance of EFIC enrollment among TBI patients and no increase in acceptance among those with a family member/loved one with TBI. The fact that black and white participants with no personal TBI experience or with a more distant connection to TBI had similar acceptance rates suggests that baseline acceptance of EFIC among these two groups is fairly similar and that the experience with the condition itself plays a role in driving the observed differences…

Read more

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Fecal transplant replants microbial garden

When facing a life-threatening infection, the “yuck factor” is a minor concern. Fecal microbiota transplant (FMT for short) has become an accepted treatment for recurrent Clostridium difficile infection, which can cause severe diarrhea and intestinal inflammation.

In a new video, Emory physicians Colleen Kraft and Tanvi Dhere explain how FMT restores microbial balance when someone’s internal garden has been disrupted.

C. difficile or “C diff” is a hardy bacterium that can barge into the intestines after another infection has been treated with antibiotics, when competition for real estate is low. In the last few years, doctors around the world have shown that FMT can resolve recurrent C diff infection better than antibiotics alone.

At Emory, Kraft and Dhere have performed almost 300 FMTs and report a 95 percent success rate when treating recurrent C diff. They have established a standard slate of stool donors, whose health is carefully screened.

Building on their experience with the procedure, Kraft and Dhere are studying whether FMT can head off other antibiotic-resistant infections besides C diff in kidney transplant patients. They have teamed up with infectious disease specialists Aneesh Mehta and Rachel Friedman-Moraco to conduct this study. Read more

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The very first cells

Please welcome cell biologist Dorothy Lerit to Emory.

Dorothy Lerit, PhD

She was the lead author on a recent Cell Reports paper on primordial germ cell formation in Drosophila, along with colleagues from NHLBI, where she was a postdoc, as well as Princeton, UVA and Columbia. Primordial germ cells are the cells that are destined to become sperm or eggs.

Germ cells are the very first cells that form out of the embryo, Lerit says. Lab Land is reminded of Lewis Wolpert’s claim that gastrulation – the separation of an apparently uniform group of embryonic cells into three germ layers — is “truly the most important time in your life.” Germ cell specification, certainly important from the viewpoint of future generations, occurs even before gastrulation.

In the Cell Reports paper, Lerit was examining the function of a particular gene called Germ cell-less; remember that Drosophila genes are often named after the effects of a mutation in the gene.

Drosophila development is superficially quite different from that of mammals. In particular, for a while the early embryo becomes a bag full of cell nuclei — without membranes separating them — known as a syncytium. This is the time when Germ cell-less function is important.

Amazing picture of germ cell formation from HHMI/Nature Cell Biology/Ruth Lehmann’s lab https://www.hhmi.org/node/16760/devel

Lerit’s background is in studying the centrosome, the place in the cell where microtubules meet, and critical for orderly cell division and for ensuring that “germline fate determinants” are sequestered to the right primordial cells.

Despite the differences between insect and mammalian embryo development, the function of Germ cell-less seems to have been conserved in evolution since problems with the human version of the gene are linked to sterility in men.

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Provocative prions may protect yeast cells from stress

Prions have a notorious reputation. They cause neurodegenerative disease, namely mad cow/Creutzfeld-Jakob disease. And the way these protein particles propagate – getting other proteins to join the pile – can seem insidious.

Yet prion formation could represent a protective response to stress, research from Emory University School of Medicine and Georgia Tech suggests.

A yeast protein called Lsb2, which can trigger prion formation by other proteins, actually forms a “metastable” prion itself in response to elevated temperatures, the scientists report.

The results were published this week in Cell Reports.

Higher temperatures cause proteins to unfold; this is a major stress for yeast cells as well as animal cells, and triggers a “heat shock” response. Prion formation could be an attempt by cells to impose order upon an otherwise chaotic jumble of misfolded proteins, the scientists propose.

A glowing red clump can be detected in yeast cells containing a Lsb2 prion (left), because Lsb2 is hooked up to a red fluorescent protein. In other cells lacking prion activity (right), the Lsb2 fusion protein is diffuse.

“What we found suggests that Lsb2 could be the regulator of a broader prion-forming response to stress,” says Keith Wilkinson, PhD, professor of biochemistry at Emory University School of Medicine.

The scientists call the Lsb2 prion metastable because it is maintained in a fraction of cells after they return to normal conditions but is lost in other cells. Lsb2 is a short-lived, unstable protein, and mutations that keep it around longer increase the stability of the prions.

The Cell Reports paper was the result of collaboration between Wilkinson, Emory colleague Tatiana Chernova, PhD, assistant professor of biochemistry, and the laboratory of Yury Chernoff, PhD in Georgia Tech’s School of Biological Sciences.

“It’s fascinating that stress treatment may trigger a cascade of prion-like changes, and that the molecular memory of that stress can persist for a number of cell generations in a prion-like form,” Chernoff says.”Our further work is going to check if other proteins can respond to environmental stresses in a manner similar to Lsb2.” Read more

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Unlocking a liver receptor puzzle

Imagine a key that opens a pin tumbler lock.  A very similar key can also fit into the lock, but upside down in comparison to the first key.

Biochemist Eric Ortlund and colleagues have obtained analogous results in their study of how potential diabetes drugs interact with their target, the protein LRH-1. Their research, published in Journal of Biological Chemistry, shows that making small changes to LRH-1-targeted compounds makes a huge difference in how they fit into the protein’s binding pocket.

First author Suzanne Mays, a graduate student in Emory's MSP program

First author Suzanne Mays, a graduate student in Emory’s MSP program

This research was selected as “Paper of the Week” by JBC and is featured on the cover of the December 2 issue.

LRH-1 (liver receptor homolog-1) is a nuclear receptor, a type of protein that turns on genes in response to small molecules like hormones or vitamins.  LRH-1 acts in the liver to regulate metabolism of fat and sugar.

Previous research has shown that activating LRH-1 decreases liver fat and improves insulin sensitivity in mice. Because of this, many research teams have been trying to design synthetic compounds that activate this protein, which could have potential to treat diabetes and nonalcoholic fatty liver disease. This has been a difficult task, because not much is known about how synthetic compounds interact with LRH-1 and switch it into the active state. Read more

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Retaining the resistance: MCR-1, colistin + lysozyme

If you’ve been following the news about antibiotic resistant bacteria, you may have heard about a particularly alarming plasmid: MCR-1. A plasmid is a circle of DNA that is relatively small and mobile – an easy way for genetic information to spread between bacteria. MCR-1 raises concern because it provides bacteria resistance against the last-resort antibiotic colistin. The CDC reports MCR-1 was found in both patients and livestock in the United States this summer.
David Weiss, director of Emory’s Antibiotic Resistance Center, and colleagues have a short letter in The Lancet Infectious Diseases showing that MCR-1 also confers resistance to an antimicrobial enzyme produced by our bodies called lysozyme. MCR-1-containing strains were 5 to 20 times less susceptible to lysozyme, they report.
This suggests that the pressure of fighting the host immune system may select for MCR-1 to stick around, even in the absence of colistin use, the authors say.
While the findings are straightforward in bacterial culture, Weiss cautions that there is not yet evidence showing that this mechanism occurs in live hosts. For those that really want to get alarmed, he also calls attention to a recent Nature Microbiology paper describing a hybrid plasmid with both MCR-1 and resistance to carbapenem, another antibiotic.

Read more

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Gestational age estimated via DNA methylation

Researchers have developed a method for estimating developmental maturity of newborns. It is based on tracking DNA methylation, a structural modification of DNA, whose patterns change as development progresses before birth.

The new method could help doctors assess developmental maturity in preterm newborns and make decisions about their care, or estimate the time since conception for a woman who does not receive prenatal care during pregnancy. As a research tool, the method could help scientists study connections between the prenatal environment and health in early childhood and adulthood.

How advanced is the development of a newborn, possibly preterm baby? Geneticists have developed a method for estimating gestational age by looking at DNA methylation.

The study, led by Alicia Smith, PhD and Karen Conneely, PhD, used blood samples from more than 1,200 newborns in 15 cohorts from around the world. The results are published in Genome Biology.

Smith is an associate professor and vice chair of research for the Department of Gynecology and Obstetrics in the School of Medicine, and Conneely is an assistant professor in the Department of Human Genetics. The first author, Anna Knight, is a graduate student in the Genetics and Molecular Biology Program.

Gestational age, is normally estimated by obstetricians using ultrasound during the first trimester, by asking a pregnant woman about her last menstrual period, or by examining the baby at birth. Ultrasound is considered to be the most precise estimate of gestational age. This work extends upon earlier studies of DNA methylation patterns that change over development and predict age and age-related health conditions in children and adults.

The Emory team gathered DNA methylation data from previous studies examining live births and health outcomes, and used an unbiased statistical learning approach to select 148 DNA methylation sites out of many thousands in the genome. By examining methylation at those sites, gestational age could be accurately estimated between 24 and 44 weeks, the authors report. The median difference between age determined by DNA methylation and age determined by an obstetrician estimate was approximately 1 week.

The researchers also found that the difference between a newborn’s age predicted by DNA methylation and by an obstetrician may be another indicator of developmental maturity, and is correlated with birthweight, commonly used as an indicator of perinatal health. Read more

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