FLC | LBNL scientists detail collaborative use of ALS in COVID-19 fight

LBNL scientists detail collaborative use of ALS in COVID-19 fight

April 15, 2020

Lawrence Berkeley National Laboratory’s (Berkeley Lab’s) Advanced Light Source (ALS) X-ray facility has been recalled to action to support research related to COVID-19.

A small team of staff at the ALS, which produces beams of X-rays and other types of light to support a wide variety of experiments for researchers from around the world, on March 31 launched several experiments for other scientists who controlled the work remotely. The specially approved ALS experiments – which were authorized by Berkeley Lab leadership – have so far been carried out by individual scientists working at separate experimental sites, known as beamlines, in the ALS facility in order to maintain social distancing. Additionally, on-site workers are taking extra precautions for safety such as regularly sanitizing equipment.

"The beamlines being used for the crystallography work developed a ‘rapid response’ capability several years ago, with remote access and automated data collection and analysis, and so were ready to hit the ground running when this crisis occurred,” said Paul Adams, director of the Lab’s Molecular Biophysics and Integrated Bioimaging (MBIB) division, which is connected to all of the beamlines and staff participating in the initial batch of approved COVID-19-related experiments. It receives support from participating members for this work, including from a large group of pharmaceutical companies across the U.S. and internationally.

Work that has been approved at the ALS includes proprietary experiments by several pharmaceutical companies: Switzerland-based Novartis, which has an office in Emeryville, California; San Francisco-based Vir Biotechnology; and Canada-based IniXium, a drug-discovery contract research organization serving the U.S. biotech industry.

Also in the first batch are crystallography experiments by a group of researchers from the lab of David Veesler, an associate professor at the University of Washington. That team is focusing on the spiky proteins on the surface of the COVID-19 virus, which the virus uses to bind to and enter host cells, and how to neutralize them. Another team, led by Daved Fremont, a professor at Washington University in Saint Louis, will be sending crystallized samples to the ALS, as will a team led by James Hurley, the Judy C. Webb chair and professor of biochemistry, biophysics, and structural biology at UC Berkeley.

Structural studies can lead to drugs that target and attack the virus while leaving other vital systems intact, for example, or that can otherwise improve the body’s defenses against the virus.

“There are proteins that are making up the virus structure and a large number of other, non-structural proteins that help in the infection cycle of the virus,” said Marc Allaire, a beamline scientist at the ALS who supports several beamlines operated by the Berkeley Center for Structural Biology.

A team led by Natalie Strynadka, a biochemistry professor at the University of British Columbia in Canada, is also expected to ship crystal samples for ALS experiments. Strynadka said her lab is collaborating with a team in Vancouver, Canada, to identify small molecular inhibitors that slow down COVID-19’s main viral protease (MPro), an enzyme that breaks down proteins into smaller forms. In related work, her lab is working with Pennsylvania-based Venatorx Pharmaceuticals and a team led by David Baker at the University of Washington to identify MPro inhibitors.

Ralf Bartenschlager, a virologist and professor at Heidelberg University in Germany, will be sending samples of COVID-19-infected cells, rendered inactive, for study using a technique known as soft X-ray tomography. In this collaborative effort, the aim is to unravel how infection by the SARS-CoV-2 virus alters the structure and organization of infected cells, with the long-term goal to identify viral and cellular targets perturbed by infection that are suitable for antiviral therapy. The experiment will be overseen by the Lab’s Carolyn Larabell, also a professor at UC San Francisco and director of the National Center for X-ray Tomography, which develops imaging technologies for biological and biomedical research.

The broader research community is welcome to apply for remote experiments relating to COVID-19 and SARS-CoV-2 at some beamlines via the National Institutes of Health-supported ALS-ENABLE program and an ALS fast-track proposal process known as RAPIDD (Rapid Access Proposals, Industry, and Director’s Discretion beam time).