Fundamental research at Weinberg College paves the way for COVID-19 breakthroughs

By Rebecca Lindell

When the COVID-19 pandemic crashed like a tidal wave around the globe in the spring of 2020, the world turned desperately to science for solutions that would quell the crisis.

So much was unknown about a virus that had emerged seemingly out of the blue. How contagious was it? What exactly did it do to the body? How could you stop the spread? Almost instantly, a global cry rose for therapies, antibody tests and a vaccine to bestow immunity to COVID-19.

The problem was that the novel coronavirus is exactly that — a brand-new disease about which very little is known. Given that scientists are still discovering new things about illnesses that have been with us for ages, what hope could there be for a rapid breakthrough with COVID-19?

A great deal of hope indeed, thanks to the fundamental research that scientists at Weinberg College and elsewhere have been pursuing for decades.

 Fundamental research is work that expands the boundaries of scientific understanding, even when there is no immediate application for the results. It’s motivated by curiosity — a gap in knowledge that leads researchers to ask, “What is that about?”

Fundamental research is ongoing, steady and persistent. It’s not the sort of work that usually leads to fame and fortune. But it does carve the path for innovations that never would have been possible had that foundational research not taken place.

Thanks to previous work by fundamental researchers, scientists around the world have been able to move quickly to better understand COVID-19 and the issues it has raised.

Professor of Chemistry Samuel I. Stupp, for example, had long been investigating how to stabilize peptides for use in regenerative medicine. Now he’s teaming with MIT researchers to determine how to use peptides to disable the coronavirus’s malignant spike proteins.

Likewise, Associate Professor of Chemistry Omar Farha has been studying nanomaterials for the past 10 years. Thanks to his prior discoveries, he has been able to pivot quickly to determine how to use the materials to create face masks that can destroy the coronavirus on contact.

Such breakthroughs don’t spring from just a few months or even years of research. They are rooted in decades and even centuries of scientists relentlessly pursuing basic questions about how the world works.

“None of us can actually forecast discovery,” says Board of Trustees Professor of Chemistry Sir Fraser Stoddart, who won the 2016 Nobel Prize in Chemistry for his development of molecular machines. “It comes with working for many years.”

Stoddart’s own discoveries were driven by his fascination with art, architecture and design, which inspired him to express his groundbreaking ideas in nanotechnology. Similarly, Stupp, Farha and other Weinberg College researchers have pursued their interests in unique directions, generating research that now has the potential to have a true impact on the COVID-19 pandemic.

And even as the fight against the coronavirus continues, other College researchers are pushing the boundaries of knowledge in other disciplines, laying the groundwork for solutions to problems that have yet to present themselves.

Meet some of these researchers here, and learn about the questions that inspire them to continue exploring.

Omar Farha: Masks that deactivate viruses on contact

 Omar Farha works with what he calls “Tinker Toys” for scientists. Except that instead of sticks and wooden spools, the “toys” are organic links joined with metal clusters so tiny that they are invisible to the naked eye.

Omar FarhaBut just like actual Tinker Toys, these metal-organic frameworks, or MOFs, have spaces between them. And these cavities create an enormous amount of surface area — thousands of square meters per gram. A handful of material made with MOFs can have a surface area the size of multiple football fields. Within that space, big things can happen.

Within their cavities, MOFs can capture extremely high volumes of gases, vapors and toxic chemical agents. They can also be manipulated to perform complex tasks. MOFs can improve the fuel efficiency of motor vehicles, deliver medicine to cells in the human body, and lengthen the shelf life of fruits and vegetables in warehouse storage containers.

Farha is intrigued by MOFs, and has learned how to combine them with textiles to create a material that would be the envy of any Marvel superhero. He recently pioneered a way to infuse textiles with MOFs that can detoxify nerve agents. This material can then be used to protect those facing chemical warfare or working with hazardous substances.

“Our material can capture highly toxic chemicals the way a bath sponge captures water when you have a spill, but more importantly our sponges can destroy [and] detoxify these chemicals,” Farha explains.

The material works in battlefield-like environments, and it stands up over time to conditions that would otherwise degrade it, such as pollutants and profuse sweat. Conditions, in fact, not so different from than those faced by exhausted medical professionals working in crowded hospital wards treating scores of patients suffering from COVID-19.

In March, as the pandemic gained steam and the shortage of hospital-grade masks, gowns and other protective equipment became severe, Farha realized that the anti-nerve-agent nanomaterial that he had developed might be able to serve another purpose. Could the material be adapted to deactivate viruses as well? After all, he thought, we already know how to kill viruses and bacteria on surfaces. What would it take to infuse his nanomaterial with antiviral capabilities?

Farha and his team set about developing a chemically modified face mask that could deactivate viruses on contact. He applied for and quickly obtained a $200,000 RAPID grant from the National Science Foundation, which has called for immediate proposals to address the spread of COVID-19.

“The goal is for the virus to disintegrate once it contacts the mask, while filtered air will pass through the mask safely,” Farha said. “These face masks will have the potential to stop or slow the spread of the highly infectious coronavirus.”

Farha said the material should be able to work both ways — protecting the wearer from virus in the vicinity, as well as protect others who may come into contact with an infected person wearing the mask.

Farha’s work provides hope for healthcare providers who have had to re-use masks and even treat patients without proper protective materials. But Farha adds that he would not be in a position to even propose this project had he not been exploring the potential of MOFs for many years prior to the pandemic.

“It was only in the last two years that we learned how to coat textiles with our smart and programmable sponges,” he said. “But it took eight years’ worth of fundamental research to figure out how and why the material works before we were able to get to the applied part of the problem.”

Yuan He: Mapping the virus at the atomic level

Assistant Professor Yuan He has always been interested in life at the atomic level.

“I’ve always felt that we know so little about our surroundings,” He says. “What does life mean, on a very physical level? I’m fascinated by that.”

He pursued that fascination while earning his PhD in biochemistry and Yuan Hebiophysics at Northwestern in 2008. As a postdoctoral researcher at the Lawrence Berkeley National Laboratory, He continued to refine his expertise in a technique called cryo-electronic microscopy. “Cryo-EM” allows researchers to visualize, at a very precise level, the molecular structure of the elements of life — just what He had always wanted to do.

He returned to Northwestern in 2015 as the Department of Molecular Bioscience’s cryo-EM specialist in structural biology — the study of the molecular dynamics of proteins, nucleic acids and uncrystalizable biological macromolecules. He gravitated toward the study of polymerase, an enzyme that synthesizes long chains of nucleic acids.

It was a fortuitous decision, as polymerase plays a key role in the evolution of viruses that cause diseases like mumps, measles and influenza — and COVID-19.

“A virus is actually a parasite,” He explains. “It can’t live without host cells. But viruses made a very clever and bold move as they evolved: they simplified the components that they need to become a parasite. So a virus’s genome is much, much smaller than that of other organisms on the planet.

“And one of the essential components that they have kept through this evolution is the enzyme polymerase, which assembles RNA molecules.”

To unlock the mysteries of this vital enzyme, He uses cryo-EM to peer directly into molecules to determine their three-dimensional shape. In February 2020, just as the pandemic was gaining steam around the globe, He and Robert Lamb, the Kenneth F. Burgess Professor of Molecular Biosciences, announced that they had, for the first time, determined the 3D atomic structure of a key complex in the virus family that includes coronavirus.

By getting a “very precise picture” of this particular enzyme, He says, researchers will eventually be able to devise therapies and drugs to shut down a virus’s ability to replicate itself. Such work has shown prior success with coronaviruses similar to the one that causes COVID-19, lending hope to researchers battling the current pandemic.

“People are interested in using the tools of cryo-EM to compare the strategies different viral branches use to do slightly different jobs,” He said. “You can almost construct an evolutionary tree of all these different viruses, because they all likely came from the same ancestor. So our research will not only allow us to fix one problem, but learn about other branches as well. And by comparing them, you can find potential weaknesses common to a lot of viruses.”

The work has the potential not only to alleviate the COVID-19 crisis, but to revolutionize other areas of healthcare as well.

“Viruses are important tools,” He notes. “Many viruses have no symptoms and cause no harm,  so we can actually use them for drug delivery. So the more we learn about them, the more we can use them for things like gene therapy and a lot of other applications.”

Samuel Stupp: Disabling spike proteins with peptides 

An expert in materials chemistry and regenerative medicine, Samuel Stupp doesn’t typically work on viruses or vaccines.

But now, Stupp is playing an integral role in work that has the potential to lead to a COVID-19 therapy or vaccine, all because he pursued fundamental research in another area entirely.

Samuel StuppStupp has conducted pioneering work with peptides — the chemical structures that are the very basis of life.

“Proteins are made out of peptides,” says Stupp, director of Northwestern’s Simpson Querrey Institute and the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine, and Biomedical Engineering. “We depend on them for everything. And we can use peptides to signal cells to do things that they would not do naturally. Peptides are a very logical way to find new therapies, and you can make an infinite number of them. They carry a language that cells understand, because they themselves are of the same chemistry.”

But peptides are tricky to work with.

“Our bodies are structured to degrade peptides,” Stupp explains. “If you make a drug out of a peptide, it disappears very quickly. You either have to modify the peptide to make it more stable, or you’d have to provide so much of it to the patient that it would be either dangerous or impractical from a cost perspective.”

Driven to solve this problem, Stupp has made impressive strides in stabilizing peptides for use in regenerative medicine, particularly when it comes to the regeneration of bone, cartilage, muscle and blood vessels. He’s also advanced treatments for neurodegenerative diseases, spinal cord injuries, diabetes and many other areas. In another focus of his laboratory, he’s pursuing fundamental research that could lead to new materials for solar energy and self-assembling catalytic systems.

So when the COVID-19 pandemic broke out, Stupp realized he might be able to help there as well, because it turns out that the spike proteins — the crown of projections that give the coronavirus its halo effect — are also composed of peptides, making them an ideal target for peptide-disabling drugs.

In fact, a team at the Massachusetts Institute of Technology had recently discovered a peptide molecule that binds to the coronavirus’s spike protein. Stupp instantly spotted the potential for collaboration and reached out to his counterparts at MIT.

“The next day, we were in touch and got going,” Stupp recalls. “It’s a great feeling, because we scientists have such a great driving force to learn new things, and we like challenges, too. I have been fascinated by all the things that I have been learning about in this area, which is not one I had ever worked in before.”

These global collaborations underline the importance of fundamental scientific research — the open-ended pursuit of knowledge that can suddenly become critical.

“When there’s a crisis, you never know what areas of science will be needed to address a specific challenge,” Stupp says. “You have to draw from many parts of science to solve problems, and it’s very difficult to predict which ones will be the most useful. This pandemic illustrates a very important point: that even though I was not focused on viral infections, I was able to use my knowledge and my experience in something else that is directly applicable to the current COVID-19 challenge.

“All of us are desperately looking for a solution, not just in the U.S., but worldwide,” Stupp adds. “We’re hoping for a vaccine, but vaccine development is a very complex process. So this really highlights the importance of constant support for scientific research. Because without research, there are no solutions.”