Safely studying dangerous infections just got a lot easier

An extremely fast new 3D imaging method can show how cells respond to infection and to possible treatments

To combat a pandemic, science needs to move quickly. With safe and effective vaccines now widely available and a handful of promising COVID-19 treatments coming soon, there’s no doubt that many aspects of biological research have been successfully accelerated in the past two years.

Now, researchers from Lawrence Berkeley National Laboratory (Berkeley Lab) and Heidelberg University in Germany have cranked up the speed of imaging infected cells using soft X-ray tomography, a microscopic imaging technique that can generate incredibly detailed, three-dimensional scans.

Their approach takes mere minutes to gather data that would require weeks of prep and analysis with other methods, giving scientists an easy way to quickly examine how our cells’ internal machinery responds to SARS-CoV-2, or other pathogens, as well as how the cells respond to drugs designed to treat the infection.

“Prior to our imaging technique, if one wanted to know what was going on inside a cell, and to learn what changes had occurred upon an infection, they’d have to go through the process of fixing, slicing, and staining the cells in order to analyze them by electron microscopy. With all the steps involved, it would take weeks to get the answer. We can do it in a day,” said project co-lead Carolyn Larabell, a Berkeley Lab faculty scientist in the Biosciences Area. “So, it really speeds up the process of examining cells, the consequences to infection, and the consequences of treating a patient with a drug that may or may not cure or prevent the disease.”

Taking cellular freeze frames

Larabell is a professor of anatomy at UC San Francisco and director of the National Center for X-Ray Tomography, a facility based at Berkeley Lab’s Advanced Light Source (ALS). The facility’s staff developed soft X-ray tomography (SXT) in the early 2000s to fill in the gaps left by other cellular imaging techniques. They currently offer the SXT to investigators worldwide and continue to refine the approach. As part of a study published in Cell Reports Methods late last year, she and three colleagues performed SXT on human lung cell samples prepared by their colleagues at Heidelberg University and the German Center for Infection Research.

Read more on the Berkeley Lab website

Image: Digital images of cells infected with SARS-CoV-2, created from soft X-ray tomography taken of chemically fixed cells at the Advanced Light Source

Credit: Loconte et al./Berkeley Lab

Understanding what makes COVID-19 more infectious than SARS

Australian and International researchers continue to have rapid access to the macromolecular and microfocus beamlines at the Australian Synchrotron to solve protein structures in the fight against COVID-19.

“Since coming out of a hard lockdown, we are now accepting proposals for other research,” said Principal Scientist Dr Alan Riboldi-Tunnicliffe.

“Because scientists can access the beamline remotely, they do not have to worry about changes to borders and travel restrictions.”

There have been a number of COVID-19 publications, which included structural information about key proteins in the virus, from the beamlines.

Instrument scientist Dr Eleanor Campbell reports that an international team of researchers led by the University of Bristol (UK) have identified a possible cause of SARS-CoV-2’s increased infectivity compared to SARS-CoV (the virus which emerged in China in 2003) , which could provide a target for developing COVID-19 therapies.

Australian collaborators included researchers from the Institute of Molecular Bioscience at the University of Queensland, who sent the samples to the Australian Synchrotron.

Read more on the Australian Synchrotron website

In search of the perfect system

Researchers take a new approach to improve widely used biotechnology tool

The unique relationship between an essential vitamin and a purified bacterial protein has been used as a valuable tool in science and medicine for several decades. Together these two molecules, known as streptavidin and biotin, form a very strong and specific interaction that is invaluable for many biotechnological applications.

Labeling molecules with biotin and detecting them with streptavidin is a common part of many lab tests and has enabled many scientific discoveries in medicine. Streptavidin and biotin are as essential to lab technicians as hammers and nails are to a carpenter. The two molecules combine to form “molecular glue” for many of the tests used to diagnose infectious diseases like HIV, Hepatitis C and Lyme disease, to discover new proteins, viruses and bacteria, and to explore how molecules function in living organisms.

Read more on the Canadian Light Source website

Image: Trapped biotin: A crystal structure of the M88 mutein, determined at the CMCF beamline at CLS, reveals how the engineered disulphide formed between Cys49 and Cys86 (green spheres) partially block the exit pathway for biotin (magenta spheres). Credit: CLS