Warren symposium follows legacy of geneticist giant

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

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

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

glycans

The sweet side of Alzheimer’s proteomics

The Alzheimer’s field has been in a “back to the basics” mode lately. Much research has focused on beta-amyloid, the toxic protein fragment that accumulates in plaques in the brain. Yet drugs that target beta-amyloid have mostly been disappointing in clinical trials.

To broaden scope and gain new insights into the biology of Alzheimer’s, Emory investigators have been making large-scale efforts to catalog alterations of brain proteins. One recent example: Nick Seyfried and Erik Johnson’s enormous collection of proteomics data, published this spring in Nature Medicine. Another can be seen in the systematic mapping of N-glycosylation, just published in Science Advances by pharmacologist Lian Li and colleagues.

“It is very exciting to see, for the first time, the landscape of protein N-glycosylation changes in Alzheimer’s brain,” Li says. “Our results suggest that the N-glycosylation changes may contribute to brain malfunction in Alzheimer’s patients.  We believe that targeting N-glycosylation may provide a new opportunity to help combat this devastating dementia.”

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Posted on by Quinn Eastman in Neuro Leave a comment

Carbohydrates not silent to immune system

Donor antibodies, administered intravenously or subcutaneously, make up a commercial product used to treat both immunodeficiencies and inflammatory or auto-immune diseases.

These preparations contain a complex mix of antibodies against glycans, the carbohydrate molecules on the outsides of cells, a Jan. 7 paper in Science Translational Medicine reveals.

At first glance, the findings are remarkable because:

A. Immunologists have long thought that carbohydrates, by themselves, are not good at provoking the immune system. (The assumption was: you need some protein for antigen presentation and getting T cells interested.) The data shows exceptions to the rule.

B. Some of the antibodies react against human carbohydrate structures. Instead of attacking them in an auto-immune fashion, they may actually be blocking viruses or bacteria from using those structures as gateways to infection.

The lab of Stephan von Gunten at the University of Bern collaborated with the National Center for Functional Glycomics led by biochemists Rick Cummings and David Smith at Emory to analyze the spectrum of carbohydrate structures bound by donor antibodies. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Oink! — Glycan receptors for flu viruses

Pigs are natural hosts for influenza viruses that can infect humans, in particular the 2009 and, going way back, 1918 H1N1 flu strains. So to understand how influenza infections spread in the body, biochemists and virologists look at pigs.

Biochemistry chair Rick Cummings’ group has a paper in PNAS this week examining the carbohydrates or glycans on the surfaces of pig lung cells, using their “shotgun glycomics” library approach. MMG graduate student Lauren Byrd-Leotis is the first author.Piglung

“The results illustrate the repertoire of specific, endogenous N-glycans of pig lung glycoproteins for virus recognition and offer a new direction for studying endogenous glycan functions in viral pathogenesis,” the team reports.

Posted on by Quinn Eastman in Immunology Leave a comment

Antiviral sugars in human milk

Biochemists Rick Cummings and David Smith have a paper in Journal of Biological Chemistry describing antiviral sugar molecules present in human milk. The first author is postdoctoral fellow Ying Yu.

Cummings and Smith are pioneers in the field of glycomics, studying the sugar molecules that decorate our proteins and coat our cells. They have found that human milk contains specialized glycans (carbohydrate linked to other molecules such as protein or lipid) that bind to influenza virus. This is separate from, and a supplement to, the adaptive immunity of antibodies and vaccines.

“The anti-flu glycans are not induced to our knowledge, but are part of a naturally occurring ‘liquid innate immune system’ in human milk,” Cummings says. “We’re very excited about this, and the availability of the human milk glycome in printed microarray formats will now allow screening for glycan binding to a wide variety of infant pathogens. This came from a single donor, so as to not complicate the matter yet, but work in progress shows that glycans from other donors have many related but also different glycans.”

He adds that his lab is finding that the glycans in human milk are different overall in complexity and makeup from those in other mammals.

Smith hypothesizes that the glycans may be functioning as “decoy receptors,” interfering with the molecules on the surfaces of human cells that viruses use to gain access.

Posted on by Quinn Eastman in Uncategorized Leave a comment