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

Reddit as window into opioid withdrawal strategies

Drug abuse researchers are using the social media site Reddit as a window into the experiences of people living with opioid addiction. Abeed Sarker in Emory's Department of Biomedical Informatics has a paper in Clinical Toxicology focusing on the phenomenon of “precipitated withdrawal,” in collaboration with emergency medicine specialists from Penn, Rutgers and Mt Sinai. Precipitated withdrawal is a more intense form of withdrawal that can occur when someone who was using opioids starts medication-assisted treatment Read more

CROI: HIV cure report and ongoing research

The big news out of CROI (Conference on Retroviruses and Opportunistic Infections) was a report of a third person being cured of HIV infection, this time using umbilical cord blood for a hematopoetic stem cell transplant. Emory’s Carlos del Rio gave a nice overview of the achievement for NPR this morning. As del Rio explains, the field of HIV cure research took off over the last decade after Timothy Brown, known as “the Berlin patient,” Read more

transcription factors

Promiscuous protein droplets regulate immune gene activity

Biochemists at Emory are achieving insights into how an important regulator of the immune system switches its function, based on its orientation and local environment. New research demonstrates that the glucocorticoid receptor (or GR) forms droplets or “condensates” that change form, depending on its available partners.

The inside of a cell is like a crowded nightclub or party, with enzymes and other proteins searching out prospective partners. The GR is particularly well-connected and promiscuous, and has the potential to interact with many other proteins. It is a type of protein known as a transcription factor, which turns some genes on and others off, depending on how it is binding DNA.

These are fluorescent droplets of the glucocorticoid receptor (GR) in red, with a coregulator protein in green. When DNA is added, the co-regulator forms its own droplets on the surface of GR droplets. Image courtesy of Filipp Frank

“It is now thought that most transcription factors form or are recruited into condensates, and that condensation modulates their function,” says Filipp Frank, PhD, first author of the paper and a postdoctoral instructor in Eric Ortlund’s lab in the Department of Biochemistry. “What’s new is that we identified a DNA-dependent change in GR condensates, which has not been described for other transcription factors.”

The results are published in Proceedings of the National Academy of Sciences. Ortlund is a co-author of the paper, along with postdoctoral fellow Xu Liu, PhD.

Understanding how the GR works could help researchers find anti-inflammatory drugs with reduced side effects. The GR is the target for corticosteroid drugs such as dexamethasone, which is currently used to treat COVID-19 as well as allergies, asthma and autoimmune diseases.

Corticosteroids’ harmful side effects are thought to come from turning on genes involved in metabolism and bone growth, while their desired anti-inflammatory effects result from turning other inflammatory and immune system genes off. Researchers want to find alternatives that could separate those two functions.

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Posted on by Quinn Eastman in Cancer, Immunology Leave a comment

Plasma cells, antibody factories

Immune cells that serve as antibody production factories, also known as plasma cells, are the focus of a recent Nature Immunology paper from Jeremy Boss and colleagues.

Plasma cells also appear in Ali Ellebedy and Rafi Ahmed’s recent paper on the precursors of memory B cells and Eun Lee’s work on long-lived antibody-producing cells. In addition, plasma cells appear prominently in Larry Boise’s studies of myeloma, because myeloma cancer cells are thought to come from plasma cells and have a similar biology.B cell methylation

The Boss lab’s paper focuses on patterns of methylation, modifications of DNA that usually help turn genes off. In comparison with resting B cells, plasma cells need to turn on lots of genes, so their DNA methylation level goes down when differentiation occurs (see graph). PC = plasma cells, PB = plasmablasts. DNAme indicates the extent of DNA methylation. Read more

Posted on by Quinn Eastman in Immunology Leave a comment