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

cryo-electron microscopy

Super-cold technique = hot way to see enzyme structure

In the last decade, a revolution has been taking place in structural biology, the field in which scientists produce detailed maps of how enzymes and other machines in the cell work. That revolution is being driven by cryo-electron microscopy (cryo-EM for short), which is superseding X-ray crystallography as the main data-production technique and earned a chemistry Nobel in 2017.

Just before COVID-19 sent some Emory researchers home and drove others to pivot their work toward coronavirus, Lab Land had a chance to tour the cryo-EM facility and take photos, with the help of Puneet Juneja, director of the core. Juneja demonstrated how samples are prepared for data collection — see the series of photos below.

Someone coming into the facility in the Biochemistry Connector area will notice a sign telling visitors and those passing by to stay quiet (forgot to take a photo of that!). The facility has electrical shielding and temperature/humidity controls. Also two levels of cooling are required for samples, since they are flash-frozen or “vitrified” in liquid ethane, which is in turn cooled by liquid nitrogen. The cooling needs to happen quickly so that ice crystals do not form. The massive cryo-EM equipment rests on a vibration-reduction platform; no music and no loud conversation are allowed during data collection.

One of the first structures obtained in this relatively new facility was the structure of a viral RNA polymerase, the engine behind viral replication. It wasn’t a coronavirus enzyme – it was from RSV (respiratory syncytial virus).

Still, cryo-EM is a way to visualize exactly how drugs that inhibit the SARS-CoV-2 polymerase – such as remdesivir or Emory’s own EIDD-2801 – exert their effects. Chinese researchers recently published a cryo-EM structure of the SARS-CoV-2 polymerase with remdesivir in Science. Read more

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

Toe in the water for Emory cryo-EM structures

Congratulations to Christine Dunham and colleagues in the Department of Biochemistry for their first cryo-electron microscopy paper, recently published in the journal Structure.

The paper solves the structure of a bacterial ribosome bound to a messenger RNA containing a loop that regulates translation. This process is important for the study of several neurological diseases such as fragile X syndrome, for example.

Christine Dunham, PhD

Dunham writes: “We are focusing on establishing this in bacteria to understand frameshifting and protein folding as a consequence of codon preference. We will then build up our knowledge to potentially study eukaryotic translational control.”

The paper neatly links up with two Nobel Prizes: the 2017 Chemistry prize for cryo-electron microscopy and the 2009 Chemistry prize for ribosome structure, awarded in part to Dunham’s mentor Venki Ramakrishnan. Also, see this 2015 feature from Nature’s Ewen Callaway outlining how cryo-EM is a must have for structural biologists wanting to probe large molecules that are difficult to crystallize.

Construction now underway in the Biochemistry Connector will allow installation of microscopes (worth $6 million) necessary for Dunham and others to do cryo-EM here at Emory, although she advises that it will be several months until they are photo-op ready. For the Structure paper, Dunham collaborated with George Skiniotis at University of Michigan; he recently moved to Stanford. Read more

Posted on by Quinn Eastman in Neuro, Uncategorized Leave a comment