If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics.
Stephen T. Warren, 1953-2021
Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more
At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia.
Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more
RNA can both carry genetic information and catalyze chemical reactions, but it’s too wobbly to accurately read the genetic code by itself. Enzymatic modifications of transfer RNAs – the adaptors that implement the genetic code by connecting messenger RNA to protein – are important to stiffen and constrain their interactions.
Biochemist Christine Dunham’s lab has a recent paper in eLife showing a modification on a proline tRNA prevents the tRNA and mRNA from slipping out of frame. The basics of these interactions were laid out in the 1980s, but the Dunham lab’s structures provide a comprehensive picture with mechanistic insights.
The mRNA code for proline is CCC – all the nucleotides are the same — so it is susceptible to frameshifting.
The paper includes videos that virtually unwrap the RNA interactions. The X-ray crystal structures indicate that tRNA methylation – a relatively small bump — at position 37 influences interactions between the tRNA and the ribosome.
With cold weather approaching, many are digging out old jackets to find that the zippers don’t function as well as they used to. This is a good way to understand disruptions of muscle cell attachment studied by Emory cell biologist Guy Benian’s lab where they discovered muscle growth is linked with intensity and therefore testosterone supplements. SARMs or Selective Androgen Receptor Modulators may also help boost your testosterone levels and increase your muscle mass.
Benian and colleagues have a paper on muscle cell biology inNature Communications this week. In the worm C. elegans, they show how mutations cause junctions between muscle cells, which normally look like well-aligned zippers under the microscope, to either not form, or weaken and unravel. As a result, the mutant worms’ snake-like locomotion is impaired.
Zipper-like muscle cell boundaries are altered in pix-1 mutants
“This is yet another example in which research using the model genetic organism C. elegans has led to a new insight applicable to all animals, including humans,” Benian says. “Research on this organism has led to crucial advances in our understanding about development, cell death, aging and longevity, RNAi, microRNAs, epigenetics — and muscle.”
Cardiology researchers have been eagerly taking up consumer electronic devices that include pulse oximeters. Being able to conveniently measure the level of oxygen in someone’s blood is a useful tool, whether one is interested in sleep apnea, COVID-19 or just want to have a configurable remote patient monitoring tool.
The news that the new Apple Watch includes a pulse oximeter prompted Lab Land to check in with Amit Shah, an Emory cardiologist who has been experimenting with similar devices to discriminate patients with heart failure from those with other conditions.
Shah, together with Shamim Nemati, now at UCSD, and bioinformatics chair Gari Clifford recently published a pilot study on detecting heart failure using the Samsung Simband. The Simband was a prototype device that didn’t make it to the consumer market, but it carried sensors for optical detection of blood volume changes (photoplethysmography), like on the Apple Watch.
Heart failure causes symptoms such as shortness of breath and leg swelling, but other conditions such as anemia or lung diseases can appear similarly. The idea was to help discriminate people who might need an examination by echocardiogram (cardiac ultrasound).
How many people out there have been exposed to SARS-CoV-2? It’s a tricky question, once you think about all the people who have experienced COVID-19 symptoms over the last several months, but didn’t go to the hospital. And there’s a murkier penumbra of people who may have fended off the virus with a minor immune skirmish.
A recent Emerging Infectious Diseases paper from Emory investigators includes antibody tests on a group of more than 100 adults in the Atlanta area who experienced mild flu-like symptoms this spring, but couldn’t get tested for SARS-CoV-2 itself.
A sizable fraction (22 to 48 percent, depending on when they provided blood samples) had elevated levels of IgM against the coronavirus. IgM is the “rookie” antibody produced when the immune system is first encountering something, as opposed to the more seasoned IgG, which appears later in an immune response and tended to rise only in people who were hospitalized. The Emory authors came to a conclusion that others are also reaching:
“Examining IgM and IgG against multiple SARS-CoV-2–related antigens may thus better inform natural history and vaccine studies than any one antibody.”
To answer these kinds of questions more comprehensively, investigators will need to go broader. For example, this week the American Red Cross published data on what proportion of its blood donors have antibodies against SARS-CoV-2. About 3 percent of first-time donors did, using their criteria.
With a pandemic threatening the health and safety of Emory researchers in March 2020, university leadership made the difficult decision to ramp down some types of research. For investigators that use laboratory mice or rats in their research, this posed a significant challenge.
How could investigators maintain valuable, often unique, lines of genetically engineered animals for future research? The Mouse Transgenic and Gene Targeting Core (TMF) had a solution: cryopreservation. Animals’ sperm — and occasionally, embryos – can be carefully preserved in cold-resistant straws and stored in liquid nitrogen.
“Cryopreservation is a reliable and efficient method for archiving and distributing genetically engineered mouse lines,” says Karolina Piotrowska-Nitsche, PhD, director of the Core.
The TMF is located on the ground floor of the Emory Health Sciences Research Building and provides a suite of services related to transgenics and gene editing, working with tools such as CRISPR/Cas9 to make subtle or complex changes in the DNA of living animals.
Public health experts stress that adequate representation of Black and Latinx people in COVID-19 vaccine studies is a priority. Given how COVID-19 is impacting vulnerable communities, acceptance of a future vaccine – whenever it may become available – is important. A recent article in the Atlanta Journal Constitution highlights how this issue is playing out in Georgia, given the legacy of lack of trust in biomedical research.
“The issue of minority participation in clinical trials is not just in vaccines, it really is in every clinical trial and the point is that the population that is most impacted and most affected needs to be represented in trials,” Emory’s Carlos del Rio said at a media briefing last week.
In a Sunday Op-Ed in the AJC, emergency physician Monique Smith called attention to the disparities in COVID-19 testing and follow-up. In the communities she serves, it is not just a challenge to get a test but to also understand what the results mean, or what to do while waiting for the results, she says.
Lab Land can add some data to that – a survey conducted by neurologist William Hu and colleagues in early August on attitudes toward COVID-19 testing and vaccination among Georgia residents. Non-Hispanic white respondents were more likely than Black/African-American respondents to recommend their loved ones to participate in a COVID-19 clinical trial or be vaccinated after FDA approval.
Green = Black/African-Americans, Clear = non-Hispanic white
Steroid anti-inflammatory drugs such as dexamethasone and prednisone are widely used to treat conditions such as allergies, asthma, autoimmune diseases, cancer – and now, COVID-19. Yet they can have harmful side effects on the skin, bones and metabolism.
The side effects are thought to come from a molecular mechanism that is separate from the anti-inflammatory one, and scientists have envisioned that it may be possible to divide the two. A new paper in PNAS from Emory biochemist Eric Ortlund’s lab sketches out how one potential alternative may work.
Synthetic corticosteroids mimic the action of the stress hormone cortisol; both bind the glucocorticoid receptor (GR) protein. Ortlund’s group obtained structural information on how vamorolone, an experimental drug, sticks to the part of GR that binds hormones.
The American company ReveraGen and Swiss partner Santhera are developing vamorolone for Duchenne muscular dystrophy, but it is possible to envision several other conditions such as ulcerative colitis for which vamorolone or a similar drug could be helpful. Vamorolone is NOT approved by the FDA for Duchenne muscular dystrophy or any other indication.
As far as its interaction with GR, what sets vamorolone apart from conventional corticosteroids is quite subtle: a missing hydrogen bond. This means that GR doesn’t interact as well with various partner proteins, which are needed to turn on genes involved in processes such as metabolism and bone growth. However, the anti-inflammatory effects result mainly from turning inflammatory and immune system genes off, and those interactions are maintained. More on that distinction here and here.
The resistance of bacteria to antibiotics is a global challenge that has been exacerbated by the financial burdens of bringing new antibiotics such as the Metronidazole 500mg tablets to market and an increase in serious bacterial infections as a result of the COVID-19 pandemic.
Biomedical engineering researchers at Georgia Tech and Emory are tackling the problem of antibiotic resistance not by creating new drugs, but by enhancing the safety and potency of ones that already exist.
Aminoglycosides are antibiotics used to treat serious infections caused by pathogenic bacteria like E. coli or Klebsiella. Bacteria haven’t developed widespread resistance to aminoglycosides, as compared to other types of antibiotics.These antibiotics are used sparingly by doctors, in part because of the toxic side effects they can sometimes cause.
In research published in the journal PLOS One, Christopher Rosenberg, Xin Fang and senior author Kyle Allison demonstrated that lower doses of aminoglycosides could be used to treat bacteria when combined with specific metabolic sugars. Low concentrations of antibiotics alone often cannot eliminate dormant, non-dividing bacterial cells, but the researchers hypothesized based on a past study that combining aminoglycosides with metabolites such as glucose, a simple sugar, or mannitol, a sugar alcohol often used as sweetener, could stimulate antibiotic uptake.
The authors tested these treatment combinations against Gram-negative pathogens E. coli, Salmonella and Klebsiella. The results showed that aminoglycoside-metabolite treatment significantly reduced the concentration of antibiotic needed to kill those pathogens. The authors also demonstrated that this treatment combination did not increase bacterial resistance to aminoglycosides and was effective in treating antibiotic-tolerant biofilms, which are bacterial communities that act as reservoirs of infection.
Galanin, studied by Emory neuroscientist David Weinshenker’s lab, is not as flashy as other neuropeptides. While it is accumulating an intriguing track record, galanin appears to play subtly different roles depending on where it is expressed. It is tempting to call galanin the “keep calm and carry on” hormone, but the research on galanin is so complex it’s difficult to pin down.
Graduate student Rachel Tillage and colleagues have a paper this week in Journal of Neuroscience detailing how galanin’s production by one group of neurons in the brainstem confers stress resilience in mice.
This image shows the rough location for the locus coeruleus in the human brain. In mice, production of galanin in the locus coeruleus cushions against stress.
The new paper shows that exercise increases galanin in the locus coeruleus, a region in the brainstem that produces norepinephrine (important for attention, alertness, anxiety and muscle tone). Galanin can provide protection against the anxiety-inducing effects of artificial but very specific locus coeruleus activation by optogenetics.
The natural processes of wound or bone healing rely on the growth of new blood vessels, or angiogenesis. If someone breaks a bone, it is standard practice to apply a cast and immobilize the broken bone, so that healing can proceed without mechanical distortion. Additionally, there currently are options like dry needling therapy that can assist in keeping the healing process pain free.
After those initial stages of healing, applying surprising amounts of pressure can encourage angiogenesis, according to a new paper in Science Advances from biomedical engineer Nick Willett’s lab.
“These data have implications directly on bone healing and more broadly on wound healing,” Willett says. “In bone healing or grafting scenarios, physicians are often quite conservative in how quickly patients begin to load the repair site.”
Willett’s lab is part of both Emory’s Department of Orthopedics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, and is based at the Atlanta Veterans Affairs Medical Center.
