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UC San Diego Scientists to Explore New Frontiers in Parkinson’s Disease Research with $7.2M Grant
9/17/2020
In August, a team of researchers at the University of California San Diego published groundbreaking back-to-back studies describing unprecedented details of a protein linked to genetically inherited Parkinson’s disease. The researchers produced the first visualizations of leucine-rich repeat kinase 2, or LRRK2, as seen within its natural environment inside the cell, as well as the first high-resolution blueprint of the protein.

The Aligning Science Across Parkinson’s (ASAP) initiative has announced support for the next phase of the research as the scientists focus on understanding the basic mechanisms underlying Parkinson’s, a neurodegenerative disorder affecting millions. ASAP’s goal is to support research that will inform a path to a cure for Parkinson’s. The three-year, $7.2 million grant will fund research across three UC San Diego laboratories and two others based in Germany. The Michael J. Fox Foundation for Parkinson’s Research is the implementation partner for ASAP and issuer of the grant, which contributes to the Campaign for UC San Diego.

“The goal of this project is to understand the basic cell biology and structure of this really fundamentally important LRRK2 molecule,” said Samara Reck-Peterson, PhD, the lead principal investigator of the project and professor at UC San Diego School of Medicine and Division of Biological Sciences and a Howard Hughes Medical Institute investigator.

“LRRK2 is a complicated molecule with a lot of moving parts, and its dynamic behavior is very likely to play a role in both its normal function and Parkinson’s pathology. Understanding how the structure of LRRK2 changes in different states and with different disease mutations will be key to developing treatments. The equipment and expertise in cryo-EM here at UC San Diego put us in a great position to visualize all of this,” said Andres Leschziner, PhD, a professor at UC San Diego School of Medicine and Division of Biological Sciences.
UCSD Researchers Discover Carbohydrate In Lungs That COVID-19 Uses To Infect
9/16/2020
UC San Diego School of Medicine researchers announced Tuesday they have discovered a carbohydrate that the SARS-CoV-2 virus uses to latch onto a cellular molecule in the lungs, which has potential implications for treatment of COVID-19 patients.

Since January, researchers have known that the novel coronavirus primarily uses a molecule known as ACE2 -- which sits like a doorknob on the outer surfaces of the cells that line the lungs -- to enter and infect those cells. Finding a way to lock out that interaction between virus and doorknob as a means to treat the infection has become the goal of many research studies.

"ACE2 is only part of the story," said Jeffrey Esko, PhD a professor of cellular and molecular medicine at UCSD and co-director of the Glycobiology Research and Training Center. "It isn't the whole picture."
COVID-19 Virus Uses Heparan Sulfate to Get Inside Cells
9/15/2020
A molecule known as ACE2 sits like a doorknob on the outer surfaces of the cells that line the lungs. Since January 2020, researchers have known that SARS-CoV-2, the novel coronavirus that causes COVID-19, primarily uses ACE2 to enter these cells and establish respiratory infections. Finding a way to lock out that interaction between virus and doorknob, as a means to treat the infection, has become the goal of many research studies.

University of California San Diego School of Medicine researchers have discovered that SARS-CoV-2 can’t grab onto ACE2 without a carbohydrate called heparan sulfate, which is also found on lung cell surfaces and acts as a co-receptor for viral entry.

“ACE2 is only part of the story,” said Jeffrey Esko, PhD, Distinguished Professor of Cellular and Molecular Medicine at UC San Diego School of Medicine and co-director of the Glycobiology Research and Training Center. “It isn’t the whole picture.”
How COVID-19 can damage the brain
9/15/2020
In the early months of the COVID-19 pandemic, doctors struggled to keep patients breathing, and focused mainly on treating damage to the lungs and circulatory system. But even then, evidence for neurological effects was accumulating. Some people hospitalized with COVID-19 were experiencing delirium: they were confused, disorientated and agitated2. In April, a group in Japan published3 the first report of someone with COVID-19 who had swelling and inflammation in brain tissues. Another report4 described a patient with deterioration of myelin, a fatty coating that protects neurons and is irreversibly damaged in neurodegenerative diseases such as multiple sclerosis.

“The neurological symptoms are only becoming more and more scary,” says Alysson Muotri, PhD a neuroscientist at the University of California, San Diego, in La Jolla.
Twist on CRISPR Gene Editing Treats Adult-Onset Muscular Dystrophy in Mice
9/14/2020
CRISPR-Cas9 is a technique increasingly used in efforts to correct the genetic (DNA) defects that cause a variety of diseases. A few years ago, University of California San Diego School of Medicine researchers redirected the technique to instead modify RNA in a method they call RNA-targeting Cas9 (RCas9).

In a new study, publishing September 14, 2020 in Nature Biomedical Engineering , the team demonstrates that one dose of RCas9 gene therapy can chew up toxic RNA and almost completely reverse symptoms in a mouse model of myotonic dystrophy.

“Many other severe neuromuscular diseases, such as Huntington’s and ALS, are also caused by similar RNA buildup,” said senior author Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine. “There are no cures for these diseases.” Yeo led the study with collaborators at Locanabio, Inc. and the University of Florida.
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