A new term in biophysics: force/time = "yank"

A group of scientists have proposed to define change in force over time as Read more

Are immune-experienced mice better for sepsis research?

The goal is to make mouse immune systems and microbiomes more complex and more like those in humans, so the mice they can better model the deadly derangement of Read more

One more gene between us and bird flu

We’re always in favor of stopping a massive viral pandemic, or at least knowing more about what might make one Read more

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Please vote in Best Image contest

Emory University School of Medicine’s Office of Postdoctoral Education has posted ten dazzling images from current Emory biomedical research here, and you can vote on your favorites (VOTE HERE). The Best Image contest sets the stage for the Postdoctoral Research Symposium on May 19. A gallery showing all ten at once — larger than what you see below– is also available at this site.

Voting lasts only until Sunday (4/23), since the three contest-winning images will be part of the abstract book and other materials, and the organizers need to complete printing orders soon.Screen Shot 2016-04-19 at 12.46.17 PM

Lab Land is looking forward to learning more about the images. For now, it is fun to guess what they are. In the gallery, each one is labeled with the name of the researcher who submitted them. Read more

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Manipulating mouse genes to order, CRISPR or old-school

Just a follow-up to last week’s announcement from the Emory Transgenic Mouse and Gene Targeting core that they are offering CRISPR/Cas9 gene editing for mice. Using CRISPR/Cas9 to produce genetically altered mice is a

Knockout_mice

Gene targeting – the 20th century way

substantial advance over the old way of doing knockouts and other manipulations (which itself won a Nobel Prize in 2007), mainly because it’s faster and easier.

To appreciate the difference, consider that the old way involves introducing DNA into mouse embryonic stem cells, and then selecting for the rare cells that take up and incorporate the DNA in the right way. Then the ES cells have to be injected into a blastocyst, followed by mouse breeding to “go germline.”

With CRISPR/Cas9, it’s possible to inject pieces of RNA that target the desired genetic changes, straight into a one-cell stage mouse embryo. Not every embryo has all the right changes, but the frequency is high enough to inject and screen. As this review explains, it’s possible to introduce mutations into three genes at once and get mice quickly, rather than make each one separately and then breed the mice together, which can take many months.

Also, because of the need for drug selection, the targeting construct in old-school gene targeting has to be a blunt instrument. That can make it hard to make subtle changes to a gene — like introduce point mutations corresponding to natural variations linked with human disease — without taking a sledgehammer to the entire gene locus. CRISPR/Cas9 takes care of that problem.

Despite the advantages of this technology, three things to keep in mind:

*Many genetically altered mice are already available “off the shelf” as part of the International Knockout Mouse/Mouse Phenotyping Consortium.

*Emory’s Mouse Core has been working with the company Ingenious Gene Targeting, and has been out-sourcing some of the tedious aspects of old-school gene targeting in mice to Ingenious, starting last year. Technicians there can generate a dazzling array of conditional knockouts. If you want your favorite gene to flip around and produce a fluorescent protein when you give the mice an antibiotic, but only in some cells — Ingenious can do that. Old school is actually still the way to go for fancy stuff like this.

*Jackson Labs in Maine also works with Emory, offering similar services, and offers a guarantee. Read more

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Measuring microbiome disruption

How should doctors measure how messed up someone’s intestinal microbiome is?

This is the topic of a recent paper in American Journal of Infection Control from Colleen Kraft and colleagues from Emory and the Centers for Disease Control and Prevention. The corresponding author is epidemiologist Alison Laufer Halpin at the CDC.

A “microbiome disruption index” could inform decisions on antibiotic stewardship, where a patient should be treated or interventions such as fecal microbial transplant (link to 2014 Emory Medicine article) or oral probiotic capsules.

What the authors are moving towards is similar to Shannon’s index, which ecologists use to measure diversity of species. Another way to think about it is like the Gini coefficient, a measure of economic inequality in a country. If there are many kinds of bacteria living in someone’s body, the disruption index should be low. If there is just one dominant type of bacteria, the disruption index should be high.

In the paper, the authors examined samples from eight patients in a long-term acute care hospital (Wesley Woods) who had recently developed diarrhea. Using DNA sequencing, they determined what types of bacteria were present in patients’ stool. The patients’ samples were compared with those from two fecal microbial transplant donors. Read more

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Beyond CF – potential byproducts of precision medicine

Just a quick comment on the potential of research being conducted by Eric Sorscher, who came to Emory from University of Alabama, Birmingham in 2015 and is now a Georgia Research Alliance Eminent Scholar. While Sorscher’s lab is working on advancing new treatments for cystic fibrosis patients who currently do not benefit from available drugs, it was intriguing to learn of potential side benefits beyond cystic fibrosis.

Cystic fibrosis is caused by mutations in the CFTR gene, which encodes a protein with important functions in cells that produce mucus, sweat, saliva, tears and digestive enzymes. But other things can impair the functioning of the CFTR protein besides genetic mutations. Namely, smoking. Read more

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From Emory scientist to California policy analyst

Don’t call them alternative careers — since most graduate students in the biomedical sciences won’t end up as professors. Since I found a career outside the laboratory myself, I like to keep an eye out for examples of Emory people who have made a similar jump. [Several more in this Emory Magazine feature, which mentions the BEST program, aimed at facilitating that leap.]

Debra Cooper, PhD

Debra Cooper, PhD

After a postdoc in Texas, former Emory neuroscience graduate student Debra Cooper was awarded a California Council on Science and Technology fellowship to work with the California State Senate staff, and is now a policy consultant there. More about her work can also be found at the CCST blog.

Describe your position as policy consultant now. What types of things do you work on? How does your experience in neuroscience/drug abuse research fit in?

As a policy consultant at the California State Senate Office of Research, I function as a bridge between policy and the technical information that informs public policy. A large component of my time is spent translating research and linking it with relevant policies and regulations. I then synthesize this information and disseminate it to the appropriate audiences through memoranda, reports, or presentations. Sometimes this information is used to advise and make recommendations for legislative ideas.

My main assignments deal with human services (i.e., public services provided by governmental organizations) and veterans affairs. As such, not every project that I work on is directly related to neuroscience, but I often find overlap between my assignments and my academic background. For instance, the intersection of mental health and veterans affairs services is an important topic that bridges my backgrounds. Even when I’m working on issues that don’t directly link to mental health, the years that I spent analyzing research and statistics comes in handy when evaluating relevant documents.

Describe your graduate research at Emory.

I had co-advisors while working on my PhD at Emory – Drs. David Weinshenker and Leonard Howell. My dissertation research focused on one question answered with two different model animals: rats (Weinshenker lab) and squirrel monkeys (Howell lab). I was studying the effectiveness of a drug, nepicastat, in reducing rates of relapse to cocaine abuse. Nepicastat blocks an enzyme (dopamine beta-hydoxylase) which is crucial for converting the neurochemical dopamine into the neurochemical norepinephrine. Both of these neurochemicals are involved in responses to cocaine, and we hypothesized that nepicastat could help in regulating these neurochemicals to prevent relapse. Read more

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An effective alternative to fecal transplant for C. difficile?

Bacterial spores in capsules taken by mouth can prevent recurrent C. difficile infection, results from a preliminary study suggest.

Clostridium difficile is the most common hospital-acquired infection in the United States and can cause persistent, sometimes life-threatening diarrhea. Fecal microbiota transplant has shown promise in many clinical studies as a treatment for C. difficile, but uncertainty has surrounded how such transplants should be regulated and standardized. Also, the still-investigational procedure is often performed by colonoscopy, which may be difficult for some patients to tolerate.

The capsule study, published Monday in Journal of Infectious Diseases, represents an important step in moving away from fecal microbiota transplant as a treatment for C. difficile, says Colleen Kraft, MD, assistant professor of pathology and laboratory medicine and medicine (infectious diseases) at Emory University School of Medicine.

Kraft and Tanvi Dhere, MD, assistant professor of medicine (digestive diseases) have led development of the fecal microbiota transplant program at Emory. They are authors on the capsule study, along with investigators from Mayo Clinic, Massachusetts General Hospital, Miriam Hospital (Rhode Island), and Seres Therapeutics, the study sponsor.

While this study involving 30 patients did not include a control group, the reported effectiveness of 96.7 percent compares favorably to published results on antibiotic treatment of C. difficile infection or fecal microbial transplant. Read more

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Wound-healing intestinal bacteria: like shrubs after a forest fire

In injured mouse intestines, specific types of bacteria step forward to promote healing, Emory scientists have found. One oxygen-shy type of bacteria that grows in the wound-healing environment, Akkermansia muciniphila, has already attracted attention for its relative scarcity in both animal and human obesity.

NMicro

An intestinal wound brings bacteria (red) into contact with epithelial cells (green). The bacteria can provide signals that promote healing, if they are the right kind.

The findings emphasize how the intestinal microbiome changes locally in response to injury and even helps repair breaches. The researchers suggest that some of these microbes could be exploited as treatments for conditions such as inflammatory bowel disease.

The results were published on January 27 in Nature Microbiology. Researchers took samples of DNA from the colon tissue of mice after they underwent colon biopsies. They used DNA sequencing to determine what types of bacteria were present.

“This is a situation resembling recovery after a forest fire,” says Andrew Neish, MD, professor of pathology and laboratory medicine at Emory University School of Medicine. “Once the trees are gone, there is an orderly succession of grasses and shrubs, before the reconstitution of the mature forest. Similarly, in the damaged gut, we see that certain kinds of bacteria bloom, contribute to wound healing, and then later dissipate as the wound repairs.” Read more

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Rescuing existing antibiotics with adjuvants

One of the speakers at Thursday’s Antibiotic Resistance Center symposium, Gerald Wright from McMaster University, made the case for fighting antibiotic resistance by combining known antibiotics with non-antibiotic drugs that are used to treat other conditions, which he called adjuvants.

As an example, he cited this paper, in which his lab showed that loperamide, known commercially as the anti-diarrheal Immodium, can make bacteria sensitive to tetracycline-type antibiotics.

Wright said that other commercial drugs and compounds in pharmaceutical companies’ libraries could have similar synergistic effects when combined with existing antibiotics. Most drug-like compounds aimed at human physiology follow “Lipinski’s rule of five“, but the same rules don’t apply to bacteria, he said. What might be a more rewarding place to look for more anti-bacterial compounds? Natural products from fungi and plants, Wright proposed.

“I made a little fist-pump when he said that,” says Emory ethnobotanist Cassandra Quave, whose laboratory specializing in looking for anti-bacterial activities in medicinal plants.

Medical thnobotanist Cassandra Quave collecting plant specimens in Italy.

Medical ethnobotanist Cassandra Quave collecting plant specimens in Italy

Indeed, many of the points he made on strategies to overcome antibiotic resistance could apply to Quave’s approach. She and her colleagues have been investigating compounds that can disrupt biofilms, thus enhancing antibiotic activity. More at eScienceCommons and at her lab’s site.

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Looking back – Lab Land Top 10 posts in 2015

Happy New Year, and thank you for reading Emory Lab Land. Here are the top ten posts during 2015, according to Google Analytics. I pledge to bring you more quirky and insightful research, striking images and explanations of hard-to-grasp concepts in 2016.

  1. Hypersomnia update: beyond subject one [post is from summer of 2014, reflects long tail/lasting interest from hypersomnia community]
  2. Anticancer drug strategy: making cells choke on copper
  3. Microbiome enthusiasm at Emory
  4. The unsweetened option [Not about iced tea, but about low-sugar diet and fatty liver disease]
  5. Fragile X regulation is a finely tuned machine
  6. Stem cell/cardiology researcher Hee Cheol Cho joins Emory
  7. There will be micro particles (in stored blood)
  8. Hypersomnia update: clarithromycin study
  9. Gabbing about GABA — implications for hypersomnia treatments
  10. Nudging physician behavior on antibiotic orders
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Metagenomics explainer

A term we heard a bunch at the Emory Microbiome Symposium in November was “metagenomics”. Time for an explainer, with some help from Emory geneticist Tim Read.

Nature Reviews Microbiology defines metagenomics as “genomic analysis of microbial DNA that is extracted directly from communities in environmental samples.”

This technology — genomics on a huge scale — enables a survey of the different microorganisms present in a specific environment, such as water or soil, to be carried out. Metagenomics is also emerging as a tool for clinical diagnosis of infectious diseases.

Read notes that the term specifically refers to “shotgun” sequencing of environmental DNA.

“The shotgun approach is to randomly sample small pieces of the DNA in the tube, no matter which organism they came from,” he says. “The output is a mélange of different genes from bacteria, viruses, fungi, plants and humans.  The data is fascinating but the analysis is daunting.” Read more

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