Study finds ‘important implications’ to understanding immunity against COVID-19

New research from Emory University indicates that nearly all people hospitalized with COVID-19 develop virus-neutralizing antibodies within six days of testing positive. The findings will be key in helping researchers understand protective immunity against SARS-CoV-2 and in informing vaccine development. The test that Emory researchers developed also could help determine whether convalescent plasma from COVID-19 survivors can provide immunity to others, and which donors' plasma should be used. The antibody test developed by Emory and validated Read more

Emory plays leading role in landmark HIV prevention study of injectable long-acting cabotegravir

Emory University played a key role in a landmark international study evaluating the safety and efficacy of the long-acting, injectable drug, cabotegravir (CAB LA), for HIV prevention. The randomized, controlled, double-blind study found that cabotegravir was 69% more effective (95% CI 41%-84%) in preventing HIV acquisition in men who have sex with men (MSM) and transgender women who have sex with men when compared to the current standard of care, daily oral emtricitabine/tenofovir disoproxil fumarate Read more

Yerkes researchers find Zika infection soon after birth leads to long-term brain problems

Researchers from the Yerkes National Primate Research Center have shown Zika virus infection soon after birth leads to long-term brain and behavior problems, including persistent socioemotional, cognitive and motor deficits, as well as abnormalities in brain structure and function. This study is one of the first to shed light on potential long-term effects of Zika infection after birth. “Researchers have shown the devastating damage Zika virus causes to a fetus, but we had questions about Read more

Neuro

Stage fright: don’t get over it, get used to it

Stage fright: don’t get over it, get used to it, advises Emory neuroscientist Anwesha Banerjee in her recent talk at TEDx Decatur. Many can feel empathy with the situation Banerjee describes. It was her first public presentation eight years ago, facing “a room full of scientists, who for whatever reason, did not look very happy that day.”

“What if I fail in front of the crowd? What if everybody thinks I’m an idiot?”

That feeling of scrutiny might have an evolutionary relationship to the fear of being eaten by a predator, she speculates.

Through participating in Toastmasters International, she has made public speaking more of a habit. She contrasts the two parts of the brain: the amygdala, tuner of emotional responses, with the basal ganglia, director of habits.

“I still get stage fright,” she says. “In fact, I have it right now, thinking how all you predators might try to eat me up! But my brain pays less attention to it.”

Banerjee is a postdoctoral scientist in cell biologist Gary Bassell’s lab, studying myotonic dystrophy. In 2017, she was funded by the Myotonic Dystrophy Foundation to create a mouse model of the neurological/sleep symptoms of myotonic dystrophy.

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Designer drugs as tools for studying brain development in non-human primates

To investigate the functions of regions within the brain, developmental neuroscience studies have often relied on permanent lesions. As an alternative to permanent lesions, scientists at Yerkes National Primate Research Center sought to test whether chemogenetic techniques could be applied to produce a transient inhibition of the amygdala, well known for regulating emotional responses, in infant non-human primates.

Their findings were recently published online by eNeuro, an open access journal of the Society for Neuroscience.

Amygdala — image from NIMH

Chemogenetics is a way of engineering cells so that they selectively respond to designer drugs, which have minimal effects elsewhere in the brain. It involves injection of a viral vector carrying genes encoding receptors responsive to the designer drug – in this case, clozapine-N-oxide, a metabolite of the antipsychotic clozapine. The technique has mostly been tested in rodents.

“This proof-of-principle study is the first to demonstrate that chemogenetic tools can be used in young infant nonhuman primates to address developmental behavioral neuroscience questions,” says Jessica Raper, PhD, first author of the eNeuro paper and a research associate at Yerkes. “Considering its reversibility and reduced invasiveness, this technique holds promise for developmental studies in which more invasive techniques cannot be employed.” Read more

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GRIN families join together for neuroscience

Editor’s note: This post was a collaboration with MMG graduate student Megan Hockman.

They were brought together by their children’s epilepsies, and by rapid advances in genetic sequencing. Only a few years ago, these families would have been isolated, left to deal with their children’s seizures and neurological problems on their own. Now, they’ve organized themselves and are shaping the future of research.

Agonist binding domains of NMDA receptors, where several disease-causing mutations can be found. Adapted from Swanger et al, AJHG (2016).

In mid-September, parents of children affected by variations in GRIN genes gathered at Emory Conference Center to meet with scientists to discuss current research. GRIN disorders occur because of mutations in genes encoding NMDA receptors, which play key roles in memory, learning and neuronal development. NMDA receptors are a type of receptor for glutamate, the main excitatory neurotransmitter in the brain. The receptors themselves are encoded by multiple genes and assemble into tetramers. When their function is altered by mutations in one of these genes, symptoms appear in infancy or early childhood, usually including epilepsy and developmental delay.

The conference was the first time several patient advocacy groups oriented around GRIN-related disorders had met together, says Denise Rehner, president of the CureGRIN Foundation and mother of an affected child. For parents, this was an opportunity to connect with each other and advocacy groups, and to interact with scientists. For researchers, it was a chance to hear from those who are being impacted by their studies, and to discuss better ways to share data.

“We got a chance to explain to all the stakeholders – patient groups, foundations, companies – exactly what we do,” said Emory neuroscientist and conference organizer Stephen Traynelis, director of the Center for Functional Evaluation of Rare Variants. Traynelis and colleague Hongjie Yuan have been tracking the direct impacts of mutations on the function of the NMDA receptor. In doing so, they plan work with clinicians to compile registries, linking specific functional data to patient symptoms.

In addition to understanding underlying mechanisms and outcomes of GRIN disorders, researchers want to figure out how to treat affected children with existing drugs. Several options exist for targeting NMDA receptors, such as dextromethorphan (a cough suppressant) or memantine, approved for symptoms of Alzheimer’s. Traynelis and Yuan previously collaborated with the Undiagnosed Disease Program (now the Undiagnosed Disease Network) at the National Institutes of Health to investigate memantine as a treatment for a child with a GRIN2A mutation, showing that the drug could reduce seizure burden in one patient. Read more

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A new term in biophysics: force/time = “yank”

Biologists and biomedical engineers are proposing to define the term “yank” for changes in force over time, something that our muscles cause and nerves can sense and respond to. Their ideas were published on September 12 in Journal of Experimental Biology.

Expressed mathematically, acceleration is the derivative of speed or velocity with respect to time. The term for the time derivative of acceleration is “jerk,” and additional time derivatives after jerk are called “snap,” “crackle” and “pop.”

The corresponding term for force – in physics, force is measured in units of mass times acceleration – has never been defined, the researchers say.

Scientists that study sports often use the term “rate of force development”, a measure of explosive strength. Scientists who study gait and balance — in animals and humans — also often analyze how quickly forces on the body change. It could be useful in understanding spasticity, a common neuromuscular reflex impairment in multiple sclerosis, spinal cord injury, stroke and cerebral palsy.

“Understanding how reflexes and sensory signals from the muscles are affected by neurological disorders is how we ended up needing to define the rate change in force,” says Lena Ting, PhD, professor of rehabilitation medicine at Emory University School of Medicine and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. Read more

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Emory Microbiome Research Center inaugural symposium

Interest in bacteria and other creatures living on and inside us keeps climbing. On August 15 and 16, scientists from a wide array of disciplines will gather for the Emory Microbiome Research Center inaugural symposium.

On the first day, Lab Land is looking forward to hearing from several of the speakers, touching on topics stretching from insects/agricultural pathogens to neurodegenerative disease. The second day is a hands on workshop organized by instructor Anna Knight on sorting through microbiome data. The symposium will be at WHSCAB (Woodruff Health Sciences Center Auditorium). Registration before August 2 is encouraged!

Many of the projects that we highlighted four years ago, when Emory held its first microbiome symposium, have continued and gathered momentum. Guest keynotes are from Rodney Newberry from WUSTL and Gary Wu from Penn.

 

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Mouse version of 3q29 deletion: insights into schizophrenia/ASD pathways

Scientists at Emory University School of Medicine have created a mouse model of human 3q29 deletion syndrome, which is expected to provide insights into the genetic underpinnings of both schizophrenia and autism spectrum disorder.

In 3q29 deletion syndrome, a stretch of DNA containing several genes is missing from one of a child’s chromosomes. The deletion usually occurs spontaneously rather than being inherited. Affected individuals have a higher risk of developing intellectual disability, schizophrenia, and autism spectrum disorder. 3q29 deletion is one of the strongest genetic risk factors for schizophrenia, and the Emory researchers see investigating it as a way of unraveling schizophrenia’s biological and genetic complexity.

The results were published in Molecular Psychiatry.

“We see these mice as useful tools for understanding the parts of the brain whose development is perturbed by 3q29 deletion, and how it affects males and females differently,” says Jennifer Mulle, PhD, assistant professor of human genetics. “They are also a starting point for dissecting individual genes within the 3q29 deletion.”

Working with clinicians and psychologists at Marcus Autism Center, Mulle is leading an ongoing study of 3q29 deletion’s effects in humans, and observations from the mice are expected to inform these efforts. (More about Mulle here.) Read more

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Head to head narcolepsy/hypersomnia study

At the sleep research meeting in San Antonio this year, there were signs of an impending pharmaceutical arms race in the realm of narcolepsy.

The big fish in a small pond, Jazz Pharmaceuticals, was preparing to market its recently FDA-approved medication: Sunosi/solriamfetol. Startup Harmony Biosciences was close behind with pitolisant, already approved in Europe. On the horizon are experimental drugs designed to more precisely target the neuropeptide deficiency in people with classic narcolepsy type 1 (for narcolepsy with cataplexy: hypocretin/orexin agonists).

Amidst this commercial maneuvering, a new clinical trial is underway at Emory Sleep Center. The study compares modafinil versus amphetamines for narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH).

These are not new drugs; they are old standards, when used to treat other sleep disorders. What’s remarkable here is that they are being tested “head-to-head.” In addition, the study explicitly tracks outcomes that people with NT2 and IH often talk about: sleep inertia, or difficulty waking up and getting out of bed in the morning, and brain fog, which is difficulty thinking/concentrating/paying attention. The main outcome measure is the Epworth Sleepiness Scale, which asks how likely someone is to fall asleep during daytime situations such as reading or while stopped in traffic. Read more

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I3 Venture awards info

Emory is full of fledgling biomedical proto-companies. Some of them are actual corporations with employees, while others are ideas that need a push to get them to that point. Along with the companies highlighted by the Emory Biotech Consulting Club, Dean Sukhatme’s recent announcement of five I3 Venture research awards gives more examples of early stage research projects with commercial potential.

This is the third round of the I3 awards; the first two were Wow! (basic discovery) and Synergy II/Nexus (promoting interdisciplinary collaboration). For the five Venture awards, the Dean’s office is providing a total of $100,000. The companies will then use the momentum to seek larger amounts of funding from various sources. Lab Land is still collecting information on the projects:

 

Faculty Name Technology Relevant links
Ray Dingledine + Thota Ganesh Pyrefin EP2 receptor antagonists vs epilepsy, pain, inflammation New class of potential drugs inhibits inflammation in brain
Mark Goodman, W. Robert Taylor Microbial Medical PET imaging agent for detection of bacterial infections Spoonful of sugar helps infection detection
Carlos Moreno + Christian Larsen ResonanceDx Miniaturized rapid creatinine test for point of care use  
Edmund Waller + Taofeek Owonikoko Cambium Oncology Enhancing responsiveness of pancreatic cancer to immunotherapy The Company’s lead compound was effective in animal studies for pancreatic cancer, melanoma, leukemia and lymphoma.
Chunhui Xu TK High-throughput screening for antiarrhythmic drugs using cardiomyocytes Fetal alcohol toxicity – in a dish // Cardiac ‘disease in a dish’ models advance arrhythmia research
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Beyond the amyloid hypothesis: proteins that indicate cognitive stability

If you’re wondering where Alzheimer’s research might be headed after the latest large-scale failure of a clinical trial based on the “amyloid hypothesis,” check this out.

Plaques. Tangles. Clumps. These are all pathological signs of neurodegenerative diseases that scientists can see under the microscope. But they don’t explain most of the broader trends of cognitive resilience or decline in aging individuals. What’s missing?

A recent proteomics analysis in Nature Communications from Emory researchers identifies key proteins connected with cognitive trajectory – meaning the rate at which someone starts to decline and develop mild cognitive impairment or dementia.

This paper fits in with the multi-year push for “unbiased” Alzheimer’s/aging research at Emory. The lead and senior authors are Aliza and Thomas Wingo, with proteomics from biochemist Nick Seyfried and company.

The proteins the Emory team spotlights are not the usual suspects that scientists have been grinding on for years in the Alzheimer’s field, such as beta-amyloid and tau. They’re proteins connected with cellular energy factories (mitochondria) or with synapses, the connections between brain cells.

“Our most notable finding is that proteins involving mitochondrial activities or synaptic functions had increased abundance among individuals with cognitive stability regardless of the burden of β-amyloid plaques or neurofibrillary tangles,” the authors write. “Taken together, our findings and others highlight that mitochondrial activities would be a fruitful research target for early prevention of cognitive decline and enhancement of cognitive stability.” Read more

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Focus on mitochondria in schizophrenia research

Despite advances in genomics in recent years, schizophrenia remains one of the most complex challenges of both genetics and neuroscience. The chromosomal abnormality 22q11 deletion syndrome, also known as DiGeorge syndrome, offers a way in, since it is one of the strongest genetic risk factors for schizophrenia.

Out of dozens of genes within the 22q11 deletion, several encode proteins found in mitochondria. A team of Emory scientists, led by cell biologist Victor Faundez, recently analyzed the network of proteins found in human cells, both from individuals affected by 22q11 deletion syndrome and their healthy relatives.

The results are published in Journal of Neuroscience. Note: this is a sprawling paper, involving both proteomics (courtesy of Nick Seyfried, whose Emory epithet is “wizard”) and mutant Drosophila fruit flies. There are four co-first authors: Avanti Gokhale, Cortnie Hartwig, Amanda Freeman and Julia Bassell.

Victor Faundez, PhD

Mitochondrial proteins are important for keeping cells fueled up and in metabolic balance, but how does altering them affect the brain in a way that leads to schizophrenia? That’s the overall question: how do changes in the miniature power plants within the cell affect synapses, the junctions between cells?

The scientists were focusing on one particular mitochondrial protein, SLC25A1, whose corresponding gene is in the 22q11 deletion. Faundez says that SCL25A1 has been largely ignored by other scientists studying 22q11.

“We think SLC25A1 exerts a powerful influence on the neurodevelopmental phenotypes in 22q11,” he says. “Our main focus forward is going to be the function that mitochondria play in synapse biology.” Read more

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