Mysterious DNA modification important in fly brain

Drosophila, despite being a useful genetic model of development, have very little DNA methylation on C. What they do have is methylation on A (technically, N6-methyladenine), although little was known about what this modification did for Read more

Where it hurts matters in the gut

What part of the intestine is problematic matters more than inflammatory bowel disease subtype (Crohn’s vs ulcerative colitis), when it comes to genetic activity signatures in pediatric Read more

Overcoming cisplatin resistance

Cisplatin was known to damage DNA and to unleash reactive oxygen species, but the interaction between cisplatin and Mek1/cRaf had not been observed Read more

Immunology

Providing the potent part of probiotics

A Emory News item on a helpful part of the microbiome focuses on how the same type of bacteria – lactobacilli – activates the same ancient signaling pathway in intestinal cells in both insects and mammals. It continues a line of research from Rheinallt Jones and Andrew Neish on how beneficial bacteria stimulate wound healing by activating ROS (reactive oxygen species).

Asma Nusrat, MD

A idea behind this research is: if we know what parts of the bacteria stimulate healing, perhaps doctors can deliver that material, or something very close, to patients directly to treat intestinal diseases such as Crohn’s or ulcerative colitis.

This idea has advanced experimentally, as demonstrated by two papers from Jones and Neish’s frequent collaborator, Asma Nusrat, who recently moved from Emory to the University of Michigan. This team had shown that a protein produced by human intestinal cells called annexin A1 activates ROS, acting through the same N-formyl peptide receptors that bacteria do.

Nusrat told me Friday her team began investigating annexins a decade ago at Emory, and it was fortuitous that Neish was working on beneficial bacteria right down the hall, since it is now apparent that annexin A1 and the bacteria are activating the same molecular signals. (Did you know there is an entire conference devoted to annexins? I didn’t until a few days ago.)

In a second Journal of Clinical Investigation paper published this February, Nusrat and her colleagues show that intestinal cells release vesicles containing annexin A1 following injury. The wound closure-promoting effects of these vesicles can be mimicked with nanoparticles containing annexin A1. The nanoparticles incorporate a form of collagen, which targets them to injured intestinal tissue. Read more

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Emory team part of undiagnosed conditions challenge

An Emory team of geneticists and genetics counselors is participating in the Clarity Undiagnosed competition, hosted by Boston Children’s Hospital and Harvard Medical School.

The team is led by genetics counselor Dawn Laney MS, CGC, CCRC. Team members include: Madhuri Hegde, PhD, William Wilcox, MD,PhD, Michael Gambello, MD, PhD, Rani Singh, PhD, RD, Suma Shankar, MD, PhD, Alekhya Narravula, MS,CGC, Kristin Cornell, MS, CRC, Cristina da Silva, MS, Sarah Richards, MS, CGC and Kimberly Lewis, MS, CGC.

In Clarity Undiagnosed, five families of patients with undiagnosed conditions provide DNA sequence information and clinical summaries to up to 30 competing teams. The teams then do their best to interpret the data and provide answers, and a $25,000 prize will go to the team that solves the mysteries in the most complete way.

At the discretion of the families, short videos of the patients may be available to investigators through producers of a forthcoming documentary film, Undiagnosed, but the teams are barred from direct interaction with the families. A glimpse of some of the families is possible by viewing the trailer. Teams have until September 21 to submit their reports and the results of the competition will be announced in November.

Boston Children’s and Harvard held a similar competition in 2012, which attracted teams from all over the world.

The competition grows out of the NIH-sponsored Undiagnosed Diseases Network; Emory pharmacologists Stephen Traynelis and Hongjie Yuan have been working with the related Undiagnosed Diseases Program based at NIH (very complex 2014 paper, blog post on personalized molecular medicine).

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Reversing liver fibrosis via adiponectin

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver conditions in the United States, affecting 30 percent of the population, and increasing — and likely to catch up in prevalence with obesity and diabetes. In NAFLD, fat content of the liver is elevated to 6 percent or more in people who drink in moderation or not at all. Patients will first present with elevated liver enzyme values in blood tests, but then an imaging test or tissue biopsy may be ordered to evaluate the extent of the damage. NAFLD is mostly asymptomatic and is variable in severity; a majority of those afflicted do not need drug treatments. However, NAFLD is thought to be a preliminary condition that can eventually progress to severe manifestations, such as cirrhosis, hepatocellular carcinoma, and end stage liver failure.

Progression of liver disease, from NIDDK.  This article is a guest post from Kristina Bargeron Clark, a graduate student at Emory and communications chair for Women in Bio-Atlanta. Her website is www.inkcetera.org.

Progression of liver disease, from NIDDK.
This is a guest post from Kristina Bargeron Clark, a MMG graduate student at Emory and communications chair for Women in Bio-Atlanta. Her website is www.inkcetera.org.

At Emory, Frank Anania, director of the Department of Medicine’s Division of Digestive Diseases, and his colleagues are developing a tool to treat liver disease. A recent publication in the FASEB Journal describes their investigation into the potential for the hormone adiponectin to modulate liver fibrosis.

Adiponectin is produced by adipose tissue, but is known to decrease in overweight people with metabolic disease. Research by others indicates that it may prevent heart and kidney fibrosis. The Emory team’s studies were conducted to determine if adiponectin could also reduce liver fibrosis.

Read more

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Bone-strengthening particles stimulate autophagy

Neale Weitzmann and George Beck have been publishing a series of papers describing how silica nanoparticles can increase bone mineral density in animals. Their findings could someday form the basis for a treatment for osteoporosis.

In 2012, we posted an article and video on this topic. We wanted to call attention to a few of the team’s recent papers, one of which probes the mechanism for a remarkable phenomenon: how can very fine silica particles stimulate bone formation?

The particles’ properties seem to depend on their size: 50 nanometers wide – smaller than a HIV or influenza vision. In a 2014 ACS Nano paper, Beck, Weitzmann and postdoc Shin-Woo Ha show that the particles interact with particular proteins involved in the process of autophagy, a process of “self digestion” induced by stress.

“These studies suggest that it is not the material per se that stimulates autophagy but rather size or shape,” they write. Read more

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A few links for BEINGS2015

Several well-known authors, scientists and bioethicists are in downtown Atlanta’s Tabernacle for the #BEINGS2015 conference. Paul Wolpe and the Center for Ethics have been central to organizing the event, and several Emory biomedical and genetics researchers will be involved in shaping the consensus documents that will emerge.

I won’t attempt to summarize the ongoing discussion at this point; with biotechnology, it is difficult to draw a circle around certain topics and say “we’re going to focus on this, but not this” and today was a good example. The border between existing agricultural biotechnology and new organisms seems hard to define.

Three interesting relevant links:

The National Academy of Sciences is launching an effort to guide decision making on human gene editing technologies such as Cas9/CRISPR

Collection of scientists’ comments on human gene editing and Cas9/CRISPR in Nature Biotechnology

Nature Chem Bio paper on engineered yeast that “paves way for home brew heroin”. Interesting role of FBI in overseeing this emerging area, and note that full production of opiates in yeast may look close, but is still not yet possible.

 

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Six beautiful images — choose your favorites

WoodruffMatthew1

Matthew Woodruff — Bali Pulendran lab

ImageJ=1.48g unit=micron

Kenneth Myers — James Zheng lab

Joshua_Strauss_OPE_Image

Joshua Strauss — Elizabeth Wright lab

AndersonJoAnna

JoAnna Anderson — Francisco Alvarez lab

AlexTamas

Alexey Tamas — Charles Searles lab

Emory’s Office of Postdoctoral Education is holding a Best Image contest. The deadline to vote is this Thursday, April 30. You can look at these beautiful images (and guess exactly what they are, based on what lab they come from), but to VOTE, you need to go to the OPE site.

This is part of the run up to their Postdoctoral Research Symposium at the end of May.

(Hat tip to Ashley Freeman in Dept of Medicine!)

Read more

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Congratulations to AAAS Mass Media fellows

Two Emory graduate students, Anzar Abbas and Katie Strong, will be spending the summer testing their communication skills as part of the AAAS Mass Media fellowship program. The program is supposed to promote science communication by giving young scientists a taste of what life is like at media organizations around the country. Both of Emory’s fellows have already gained some experience in this realm.

Abbas, a Neuroscience student who recently joined brain imaging number cruncher Shella Keilholz‘s lab, will be at Howard Hughes Medical Institute. He is part of the group that recently revived the Science Writers at Emory publication In Scripto.

Strong, a Chemistry student working with Dennis Liotta on selective NMDA receptor drugs, will be at the Sacramento Bee. She has been quite prolific at the American Journal of Bioethics Neuroscience and its Neuroethics Blog.

(Thanks to Ian Campbell, a previous AAAS Mass Media fellow from Emory who worked at the Oregonian, for notifying me on this!)

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Next generation sequencing roundup

The increasing clinical use of next generation sequencing, especially whole exome and whole genome, continues to be a hot topic. The ability to contribute to diagnosis, clinical utility, incidental findings and whether insurance will cover next-gen sequencing are all changing.

A Nature Medicine article lays out a lot of the emerging business issues on next-gen sequencing. On the topic of incidental findings, Buzzfeed science editor Virginia Hughes last week reported stories of women who receive a cancer diagnosis as a result of having a prenatal genetic test.

“These cases, though extremely rare, are raising ethical questions about the unregulated – and rapidly evolving – genetic-testing industry,” Buzzfeed says.

At a recent Department of Pediatrics seminar, Emory geneticist Michael Gambello described examples of how whole exome sequencing, performed to diagnose intellectual disability or developmental problems in a child, can uncover cancer or neurodegenerative disease risk mutations in a parent. The question becomes, whether to notify the parent for something that may or may not be actionable. This is why Emory Genetics Laboratory’s whole exome sequencing service has an extensive “opt-in/opt-out” consent process.

Emory Genetics Laboratory executive director Madhuri Hegde, working with the Association of Molecular Pathology, has been a leader in pushing genetic testing laboratories to adopt best practices. Read more

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Threshold for long-term marijuana effects on lung function

Intuition may suggest that smoke is bad for the lungs, whether it comes from a campfire or from tobacco or marijuana. A practical question is: how bad is an occasional joint, compared with some background level of air pollution and the lungs’ ability to cope?

Since a few states have been loosening restrictions on marijuana, a group of Emory pulmonologists – Jordan Kempker, Eric Honig, and Greg Martin — decided to look at the long-term effects of marijuana smoking on lung function. Their findings, published in the Annals of the American Thoracic Society (PDF), have already attracted some attention. Read more

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Unexpected mechanism for a longevity lipid

The idea that particular lipid components, such as omega-3 fatty acids, promote health is quite familiar, so the finding that the lipid oleoylethanolamide or OEA extends longevity in the worm C. elegans is perhaps not so surprising. However, a recent paper in Science is remarkable for what it reveals about how OEA exerts its effects.

Scientists at Baylor College of Medicine led by Meng Wang, with some help from biochemists Eric Ortlund and Eric Armstrong at Emory, discovered that OEA is a way one part of the cell, the lysosome, talks to another part, the nucleus. Lysosomes are sort of recycling centers/trash digesters (important for autophagy) and the nucleus is the control tower for the cell. The authors show that starting in lysosomes, OEA travels to the nucleus and activates nuclear hormone receptors (the Ortlund lab’s specialty). Read more

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