Invisible enemy unveiled by Montana lab researchers

Perry Backus Ravalli Republic
Monday, April 13, 2020

HAMILTON (AP) — Researchers at Rocky Mountain Laboratories have been working hard to put a face on an invisible enemy that has turned the world upside down.

Using electron microscopes capable of producing images of a virus 10,000 times smaller than a human hair, the scientists have provided researchers around the world with invaluable information on the inner workings of the novel coronavirus.

The colorized images of the virus also offer the public an up-close view of something that can be hard for many to imagine, The Ravalli Republic reported.

One of the first images widely disseminated by RLM displays a series of yellow dots against a background of blues and purples. The yellow dots are the coronavirus shedding off a cell cultured at the laboratories from one of the first patients inflicted with COVID-19 in the United States.

“The virus is a very small part of a cell,” said RML’s Research Technologies Branch interim chief Beth Fischer, who leads the laboratories’ microscopy unit. “Most people don’t have an idea of scale. It’s something that we look at all the time.”

“In this case, we are sharing an image of what to many is an invisible enemy,” she said. “Hopefully, it can take a bit of mystery out of the adversary and give people something they can actually visualize.”

While the beautifully colored images of the virus have appeared in countless news stories, they aren’t an exact replication of how it would appear inside a human body.

The images captured by the Hamilton laboratories’ highpowered electron microscopes initially appear in black-andwhite images similar to the negatives from the old days of film.

From there, a close collaboration of science and art come together to enhance the images in a way that’s both beautiful to view and useful for researchers hoping to unlock secrets that could help defeat the spread of the virus.

Fischer and others in microscopy lab work closely with specially trained artists who colorize the images in ways that help scientists identify crucial elements on the interaction between the virus and cells. For example, the artist can color portions of an image to help a scientist identify how and where a virus or bacterium enters and attacks a cell.

“When they are in grayscale, most people wouldn’t know what they are looking at,” Fischer said. “The color draws the eye to a region of interest. I think it brings them to life a little bit.”

Hamilton’s RML has a long history with electron microscopes. One of the first commercially developed devices was installed at the lab in the 1950s.

Today National Institute of Allergies and Infectious Diseases scientists at the lab use heavy-duty electron microscopes to show either the surface of a sample using a scanning electron microscope (SEM), or what’s occurring inside a sample using a transmission electron microscope (TEM).

Scanning electron microscope images work well to show where and how a virus or bacteria may enter or leave a cell. Transmission electron microscope images show what the pathogen does once it’s inside and how they manipulate the cell to reproduce and spread.

“TEM is kind of like slicing a loaf of bread, pulling out a slice and examining that,” Fischer said.

RML researchers can also use a process called cryo-EM that freezes deactivated virus before looking at it through an electron microscope. It offers scientists an opportunity to study the virus in something closer to its native form.

“We don’t dehydrate them,” she said. “It’s like looking at a grape instead of a raisin.”

Through the use of this sophisticated technology, the hope is to develop a better understanding of what sets the novel coronavirus apart from its earlier counterparts, MERS (Middle East respiratory syndrome) and SARS (severe acute respiratory syndrome).

“Even though they all kind of look the same, there is something very different about them,” Fischer said. “In this case, it’s the way this virus is being easily transmitted between people. MERS had a higher mortality rate and SARS definitely did, too.”

“We are comparing their structures and looking to see what’s different about them,” she said.

In general, microscopy offers researchers a chance to see how a pathogen — whether it be a virus or bacterium — interacts with a human cell.

“We can look to see how it gets into a cell and what it harnesses inside the cell to make more of itself,” Fischer said. “We can get a lot of clues by looking inside a cell and also what happens when they escape the cells and begin to spread to other cells.”

“When you break down the basic science, you start understanding what things you may be able to target to prevent the success of the pathogen,” she said.

RML virologists and other researchers have been working seven days a week since the outbreak to put that science to work in developing vaccines and therapies.