COVID-19

Connecting the World Through the Cloud

December 3, 2020 By Becca Wolf in Research Tags: bioinformatics, COVID-19, high-throughput phenotying

Maria Clare Lusardi, an undergraduate student in the Mendoza lab, uses the cloud, a program apart of CyVerse. | photo by Becca Wolf, Bond LSC

By Becca Wolf | Bond LSC

Clouds come in many shapes and sizes. Some are big and fluffy, others dark and ominous.

Or, as in David Mendoza’s case, the cloud is a hub of experiment information.

Mendoza, an associate professor of plant sciences and scientist in Bond Life Sciences Center, recently joined the CyVerse, a cyberinfrastructure system used by Mendoza’s lab that acts as and allows his team and collaborators to see data in real time. CyVerse, funded by the National Science Foundation, allows life science researchers to share and store their research data in the cloud.

This sort of system has come in quite handy for Mendoza as the Covid-19 pandemic limited the number of people allowed in a lab last spring, forcing him to look for a better way to work remotely but still together.

“These difficulties make you more creative. Covid-19 is a serious, terrible thing, and I could tell my lab was frustrated because they wanted to continue working, but couldn’t because of the restrictions,” Mendoza said. “We needed this. We started implementing the cloud and the opportunities to keep working and collaborate continued and worked out nicely.”

Mendoza connected the cloud to the robots his lab uses to take photos of experiments. These photos are sent every other hour to the cloud, so Mendoza and collaborators can check in on experiments from anywhere in the world.

To get connected, Mendoza brought in Drew Dahlquist, an undergraduate student, to help.

“As a computer science student, the stuff I’m doing feels very natural, but I didn’t realize how much other areas of science could use it. Before I came on, they were storing all the images just on a laptop in the lab and sending them around on thumb drives, which can be very inefficient,” Dahlquist said. “It’s going to greatly improve what David’s doing in the lab.”

Dahlquist has been transferring Mendoza’s data from the thumb drives to the cloud, a process he plans on being done with by the end of the semester.

“Hopefully, I can start tweaking it a little more to refine it and then just see what other needs pop up in the future,” Dahlquist said.

The Project

The main task benefitting from this new approach is a high-throughput phenotyping project, led by Landon Swartz, an undergraduate student in his lab.

“I was kicked off campus when we had quarantine last semester, so all of my projects stopped suddenly,” Swartz said. “I was just stuck at home doing remote stuff, which was not helpful. So that’s where Drew came in to do the cloud stuff. We realized that this is going to be a regular thing for the next few years and will likely happen again in the future.”

The cloud helps Swartz and Mendoza because instead of waiting a week to see how an experiment is doing, it receives frequent updates, so they can make changes to an experiment in real time instead of after the fact.

This is beneficial when they observe how leaf color changes when over or underexposed to nutrients like iron. This can cause chlorosis — when the leaves turn yellow from lack of iron and die. The cloud allows them to see if chlorosis is occurring at a different rate than they expected. With this information, they can change the parameters and continue the experiment without any issues.

“We are establishing protocols where first thing in the morning the machine is going to send me an email with the first photo of the day and to say that the robots are okay. Then, at night before bed, I’ll get the last picture of the day,” Mendoza said.

The camera used to take photos of experiments in the Mendoza lab. These photos are then sent to the cloud. | photo by Becca Wolf, Bond LSC

Collaboration made Easy

In addition to making experiments more accessible for the Mendoza lab, the cloud allows the lab to easily share data with collaborators.

“We started to realize that having our phenotyping robots be controlled remotely or be able to put our data onto the cloud would be super useful, not just for our lab, but also for labs around the world,” Swartz said. “So, maybe the U.S. goes into quarantine, but we have a sister lab in South Africa that is able to pick up our data where we left off and continue to run experiments for us.”

Having multiple labs look at the data at the same time helps create more ideas and exposes more people to those ideas.

“Our goal is to put the data out there and let more people try different approaches to analyze the data so that all of us as a field, can decide what is the best way to do standardized experiments,” Mendoza said.

Also, with the sister lab on another continent, there are people who can check in on the experiments around the clock.

“For instance, the lab in South Africa can see the data in real time. They can see if we need to change the light, increase the light, or make the night longer, and they could also control the nutrients among other things,” Mendoza said.

The cloud will only help experiments in the future.

“The internet is a great resource to collaborate. It’s not often used like that, but we can put data that we’re getting in the moment into this huge database that anyone across the world can look at. It really changes the whole game of science,” Swartz said. “It’s no longer about who can publish things first, it has really become an everyone’s in it together kind of thing. And that’s where I really would like to see this go, and especially in the next 10 or 20 years.”

While it started because of a pandemic, Mendoza sees it as a useful tool regardless of lab restrictions.

“Now that we’ve seen the possibilities, I don’t think we’re going back just because of the amount of experiments that you can do,” Mendoza said. “We actually plan on building more machines with more sensors, so it’s not going away anytime soon.”

Beyond the Vaccine

September 25, 2020 By Lauren Hines in Research Tags: COVID-19, virology

Lucas Woods from the Weisman lab watches lung cancer cells and oral epithelial cells grow. | photo by Lauren Hines, Bond LSC

By Lauren Hines | Bond LSC

Vaccine development remains a central goal to get the current COVID-19 pandemic under control. While vaccines are highly vital in the fight against the current pandemic, what if scientists could prevent the virus from entering cells altogether? Researchers at Bond Life Sciences Center are working to do just that and, so far, they’re the only ones at Mizzou on the case.

For the Gary Weisman lab, that starts with their study of a family of purinergic receptors which are found on the plasma membrane of cells. Molecules outside the cell bind to receptors and serve as signals to trigger an action, whether it’s transporting something into a cell, alerting its defenses or initiating programmed cell death. The specific receptors they study sound off one of the first alarms to alert host immune cells when a cell is damaged.

Weisman, Bond LSC principal investigator and Curators’ Distinguished Professor of biochemistry, noticed that the spike protein in the virus that causes COVID-19, SARS-CoV-2, shares an amino acid sequence — arginylglycylaspartic acid or RGD — with one of the receptors his lab studies named, P2Y2.

“So, we had this one niche that no one I think has followed,” Weisman said. “Even though people understand RGD sequences are important for protein to protein interactions, and possibly viral entry, no one has looked at this with respect to coronaviruses.”

While ACE2, a plasma membrane receptor, serves as the primary cell-surface receptor for SARS-CoV-2 binding, a potential role for the RGD sequence in the spike protein is to bind to alternate receptors and subsequently enhance viral infectivity.

“We postulated that if there was a way to use our receptor, it might be to block the entry of the virus,” Weisman said. “The virus can’t replicate on its own. It has to get inside the cell to be replicated, so if we prevent the entry, we can potentially stop the infections.”

They found plasma membrane receptors like ACE2 and P2Y2 all share this sequence that binds to other cell-surface receptors called, integrins. The lab is currently exploring ways to block these pathways without blocking other functions.

Few other labs have made this connection because RGD is not known to be present on many of the membrane receptors. In addition, the Weisman lab already has the supplies and connections to study these receptors.

“We, as the lab, have been studying this receptor and this family of receptors for so long that if there is a lab that has the tools and the knowledge to answer this question, I definitely think that is us,” said Kevin Muñoz Forti, Ph.D. candidate for the department of biochemistry.

Kevin Muñoz Forti is doing cell culture work in “the hood,” which is a space used to prevent researchers and other outside factors from contaminating the cells. | photo by Lauren Hines, Bond LSC

The lab partners with Kamal Singh, assistant director of the Molecular Interactions Core at Mizzou and associate research professor in the department of veterinary pathobiology, who works with viruses in a way that won’t infect workers.

Singh achieves this by using look-alikes, or pseudovrises, of the spike protein on SARS-CoV-2. To the cell, this mimics the outer shell of SARS-CoV-2, but is not contagious.

Even though the Centers for Disease Control and Prevention and Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, expect a vaccine soon, this work is for the long run.

“I can guarantee you this isn’t the last coronavirus that will come up,” Singh said. “There will be many because it has been kind of periodic lately. Coronaviruses have been emerging, so the research done in collaboration with Gary’s lab will definitely be available for… future coronaviruses.”

Coronaviruses are a family of viruses which may cause respiratory illness in humans. The most recent diseases, before COVID-19, caused by previous coronaviruses were Severe Acute Respiratory Syndrome (SARS) from 2002 and Middle East Respiratory Syndrome (MERS) from 2012. Severe Acute Respiratory Syndrome Coronavirus 2 is the virus that causes COVID-19.

“This is the virus that causes COVID-19 or SARS-CoV2,” said Lucas Woods, Weisman research lab manager. “If this type of research were to have been investigated during the first coronavirus epidemic, there might have been some type of lead on the type of work we’re doing… so, absolutely this work will be useful after a vaccine or treatment is available.”

Looking ahead, the study has two years of funding from the American Lung Association in addition to grants from the National Institutes of Health. The Weisman lab hopes to eventually make it to clinical trials, but the road from basic research to clinical trials is long and arduous.

“What’s on our side, at least for the future, is that with some of these pathways we’re looking at, there are already available drugs that target these particular pathways,” Woods said.

These pathway-blocking drugs aren’t approved for humans yet, but this research could facilitate clinical scientists to test the safety of these or related drugs in humans.

The Weisman lab’s research of P2 receptors can be applied to many systems in the body and other diseases. This also allows for more ways to receive grants to fund studies longer. Along with the COVID-19 studies, they study P2 receptors in diseases that affect salivary glands.

Cheikh Seye, Mizzou professor of biochemistry, studies vascular diseases that relate to the receptors studied by the Weisman lab. Seye understands that one of the complications of COVID-19 in humans is vascular related.

“I mean there’s a lot of interaction between the vasculature and other systems, so it doesn’t stay with the salivary gland,” Seye said. “It’s all interconnected, so that’s why we need to have a multi-dimensional approach.”

In addition, the lab has found commonalities between oral and lung epithelial tissue that may contribute to COVID-19.

While this study has quite a bit of potential, it’s a long way away from seeing practical results.

“All the people in the lab have confidence because they have been successful on their own doing this before,” Weisman said. “So, it’s just another challenge, but we know how to get the answers, we have the tools and we’re optimistic that we’ll find out something.”

Researchers working on this study include Gary Weisman, Kamal Singh, Lucas Woods, Cheikh Seye, Jean Camden and Kevin Muñoz Forti.

A Big Load: Using Wastewater to Test For COVID-19

September 11, 2020 By Becca Wolf in Research Tags: COVID-19, RNA

Marc Johnson collecting pellets in his lab. | photo by Becca Wolf, Bond LSC

By Becca Wolf | Bond LSC

There is not much thought that goes into using the bathroom. You do your business, flush, and wash your hands. It is just a part of the daily routine.

Recently though, human waste has become a golden nugget to researchers. In fact, waste from toilets throughout the community are contributing to figuring out where the next COVID-19 outbreak could happen.

And Marc Johnson, Bond Life Sciences Center principal investigator and MU professor of molecular microbiology and immunology, is the person figuring out how this human waste can be an asset as he processes samples from the sewer systems of more than 70 communities across the state.

A map of the sewersheds Marc Johnson’s lab receives samples from. | map contributed by Marc Johnson

These samples may be able to serve as the canary in the coal mine before large outbreaks strike in a community, allowing health officials to prepare for and potentially prevent the spread of COVID-19.

SARS-CoV-2, the virus that causes COVID-19, appears in wastewater several days before an infected person shows symptoms, so Johnson wants to find a faster way to test for the virus.

“We’re very good at predicting what’s happening right now based on samples we collected five days ago,” Johnson said, “We are predicting the future, we just don’t know what our prediction is until the future is actually here.”

This data may not seem helpful, however, it proves that the COVID-19 case numbers are accurate and, if acted upon quickly, can prevent an outbreak in a concentrated population such as prisons or schools.

“With the students, when you’re talking about patients that don’t necessarily know they’re infected, it can be really helpful to have a heads up that this dorm has some infections even if they don’t know it,” he said.

Testing wastewater for SARS-CoV-2—an RNA virus—consists of two phases. Phase one is obtaining the sample and phase two is RNA extraction.

Starting phase one, Johnson receives a 24 hour composite from a wastewater testing facility, “So that no matter when, it doesn’t matter whenever people go, as long as they go once a day we’ll catch them,” he said. This gives his lab a representative sample of the population.

Once the sample is taken from a wastewater treatment facility, it is put into a courier system that brings it to the state lab in Jefferson City, Mo. After it arrives there, the Missouri Department of Natural Resources brings them to Johnson’s lab at Bond LSC so he can begin phase two, RNA extraction.

In Johnson’s lab, the samples are put through a filter that nothing bigger than a virus can get through. This eliminates the solids and other bacteria in the wastewater. Next, a chemical is added that allows the viral particles to stick together so they can be pelleted.

This is then put in a centrifuge and is spun for a few hours to get a small, invisible pellet. RNA is then extracted from this pellet in a QIAcube, a robot Johnson’s lab purchased for this project. The QIAcube is the same robot used by the Missouri Department of Health Services for COVID-19 testing in their own facilities.

Marc Johnson placing the samples in the QIAcube. | photo by Becca Wolf, Bond LSC

After Johnson extracts the RNA, the samples are sent to Chung-ho Lin, MU research associate professor at the College of Agriculture, Food and Natural Resources, who continues testing.

This whole process takes about five days.

Johnson hopes that test results will soon go public so people have an idea of where outbreaks are, although reading the data can be confusing.

Said Johnson, “I think we all agree we’ll be better if we put the data out the way we want it to be seen, because it’s just when you look at the raw numbers, without understanding how to interpret it, you can make any conclusion you want.”

It will be a learning curve for the public to be able to understand the data. Johnson even struggled with it at first, “We learned this lesson the hard way,” he said, “I freaked out several times where I thought I had just discovered Armageddon going to our state, but you have to put it in perspective. When you figure out how much it actually takes to get a signal and how big the sewer shed sample is, it’s like, ‘No okay, that’s normal.’”

Along with other testing sites, Johnson’s lab has been testing several universities and colleges in the state, including MU. With time and improvements, it is realistic that his lab will be able to predict the number of infected patients in an area.

“It’s a crap ton of work,” Johnson said, “But it’s kind of interesting. It worked far better than I would have expected.”

While research on COVID-19 was not on Johnson’s agenda earlier this year, he has been trying to have fun with it.

“The puns are unending,” he said, “There are just so many great puns I’ve gotten out of it.”

“It’s serious research but it’s nice that the topic has gotten a little bit of levity.”

Shifting Focus: HIV researcher takes on COVID-19

May 19, 2020 By Becca Wolf in Research Tags: COVID-19

Marc Johnson | photo by Roger Meissen, Bond LSC

By Becca Wolf | Bond LSC

Marc Johnson’s research focus changed suddenly one day this February when he received a shipment. That package of synthesized SARS-COV2 spike genes — the virus that causes COVID-19 — has now taken him down a new path.

“It was unusual, nothing like this has ever happened to me before,” Johnson said, an MU professor of molecular microbiology and immunology and Bond LSC investigator. “I’ve never had to switch directions so abruptly before but, you know, we’re always taking on new projects and shifting, it just usually doesn’t happen as fast.”

Typically, Johnson can be found in his lab studying viral glycoproteins, proteins with sugar attached to them involved in structural functions of the cell wall, and spikes, the knobby proteins on the surface of a cell. His main focus is studying HIV and its interaction with its host. However, his lab got to work right away to apply what they know to find a way to block SARS-COV2, and ultimately, COVID-19.

To do this, they focused on what they know best: glycoproteins and spike.

SARS-COV2 shares both of these features, and, in fact, Johnson has done previous research on other coronaviruses. Glycoproteins and spike allow the virus to attach to other cells. He infects cells with a safe, stripped virus containing the SARS-COV2 Spike and uses trial and error to see what works and what does not.

Early on making the glycoprotein functional was a challenge. Sometimes, when a protein of one virus is taken and stuck on another virus, it does not work. That was the case with SARS-COV2. He decided to cut of the tail of spike to see what happens.

“Most of its [spike] on the outside of the virus. There’s still a little piece on the inside, and if you make the virus smaller they don’t have that inside piece and often work better,” Johnson said, “I couldn’t get anything to work until I made that truncation.”

Without much of the tail, Johnson started looking for ways to block the virus. He has used many methods to find an effective blocking technique.

“We’ve thrown various peptides on and we’ve tested various small molecules,” Johnson said. “We’ve also tried plasma from patients who have recovered to see if they’re producing neutralizing antibodies and, no surprise, they are.”

Antibodies are crucial because they are a sign that someone has an effective defense against the virus. At the very least, antibodies allow the body to keep future infections in check. Taking antibodies from one patient and placing them in another patient passively transfers resistance to a virus and, often, immunity. Researchers are conducting studies to see if this is an effective way of blocking COVID-19.

Having only worked on COVID-19 for three months, there is still a lot Johnson—and the world—does not know.

“80% of people are just like, ‘Yeah, whatever, I’m fine,’ and then others just fall off the deep end. But, we don’t know what’s different. We don’t know why some patients do so poorly and others just shake it off,” he said. “It’s different than anything I’ve ever worked with before. I wake up every morning and it seems like there’s a new discovery every day.”

Working on COVID-19 is much different than working on other viruses, such as HIV. Many scientists are now putting manuscripts of their research online before they are published in hopes of aiding others.

While Johnson is aware that the sooner a vaccine is developed, the better, he knows not to rush things.

“It’s not about having a vaccine, it is about making sure that it’s safe and effective,” Johnson said. “We’re acutely aware that there’s this backlash against vaccines even when they are safe. If you put out one vaccine that wasn’t safe, you would ruin it for all vaccines for generations.”

For now, the search to stop COVID-19 continues and Johnson hopes his work helps come up with a treatment soon.

“We haven’t found a magic bullet yet, but we’ve seen some inhibition with various compounds,” Johnson said, “So it’s a starting point.”

Treating COVID-19: Bond LSC lab explores effectiveness of remdesivir and other potential drugs

April 30, 2020 By Jerome Duggan in Research Tags: COVID-19, Kamal Singh, viruses

By Jerry Duggan | Bond LSC

As countries hang their hopes on the drug remdesivir for battling COVID-19, recent modeling and computer-aided drug evaluation at the University of Missouri caution to keep an open mind to other drug treatments.

Kamlendra Singh at MU’s Bond Life Sciences Center assessed remdesivir and several other drugs for long-term success in treating coronavirus causing the pandemic across the world. His results were published April 26 in the journal Pathogens.

“Remdesivir is working against COVID-19, but these other drugs are in no way inferior to it,” said Singh, the assistant director of the MU Molecular Interactions Core, Bond LSC investigator and MU associate research professor of Molecular Microbiology and Immunology in the School of Medicine. “They are all FDA approved and we believe, based on our research, that they are worth looking into as a form of treatment.

Working with colleagues at the Karolinska Institutet in Stockholm, Sweden, where he has an appointment, Singh and his team started their COVID-19 specific research in earnest on February 20. Through a combination of bioinformatics, molecular modeling and computer-aided drug design, they evaluated antiviral medicines remdesivir, favipiravir, 5-Fluorouracil and ribavirin for their effectiveness against COVID-19, and possible resistance under pressure of these compounds.

While Singh agrees that remdesivir works against COVID-19, he sees potential weaknesses of the drug and believes alternatives could supplement its use.

The team first assessed at the Gilead pharmaceutical remdesivir to inhibit SARS-CoV-2 viral polymerase, an antiviral drug originally used to treat Ebola. Remdesivir is one of the most highly touted drugs at this point in the fight against COVID-19. But Singh’s findings indicate SARS-CoV-2, — the causative agent of COVID-19 — is capable of mutating — that is, developing alterations in its genome — that could help it develop resistance to the drug.

Armed with this conclusion, Singh’s team looked at three additional compounds to treat the virus. With T-705, also known as favipiravir, they concluded COVID-19 could also develop resistance, but its past effectiveness as a broad-spectrum inhibitor of RNA viruses made it worth a look as a potential option to treat COVID-19. Favipiravir, which has been approved in Japan as an anti-influenza drug, was recently approved in Italy and China for treatment of COVID-19. Favipiravir is currently undergoing testing regarding its viability against COVID-19 and results are pending.

Additionally, Singh’s lab conducted research on two other broad-spectrum RNA polymerase inhibitors: 5-Fluorouracil and ribavirin. Singh examined 5-Fluorouracil because RNA polymerase (the enzyme that copies the virus genome) from SARS-CoV-2 is structurally similar to the RNA polymerases from human Rhinovirus and Foot-and-Mouth disease viruses and 5-FU shows effectiveness against these viruses. Due to this structural similarity, it stood to reason that 5-Fluorouracil may also have some effectiveness in treating COVID-19.

Ribavirin — one of the most widely used, broad spectrum inhibitors of RNA-viruses — shows unique properties that make it a prime candidate to bind to the active site of COVID-19. By binding to the active site, ribavirin theoretically could stop the replication of the viral genome and slow the spread of COVID-19 within an individual’s body. Still, doubt remains regarding its effectiveness since the virus can likely develop resistance to ribavirin through mutations or other mechanisms.

Singh has been working on coronaviruses — a broader category of viruses of which COVID-19 is just one specific manifestation — since his arrival at MU in 2009, so he is no stranger to this area of research. His broad goal is to ultimately have his research discoveries “make a difference in the lives of patients.”

He started his work on COVID-19 with the same goal in mind.

“I did not start my research on COVID-19 in order to write this paper and have it published,” he said. “I just wanted to do my part and spend some time researching compounds that could potentially be effective against COVID-19.”

As detailed as Singh’s findings are, he is quick to acknowledge that he is part of a global scientific community and had a team of professionals within his lab, especially Dr. Kyle Hill (a postdoctoral associate) that helped him to complete this work.

“This progress is not made by individuals, but by teams,” he said. “I have a talented group of individuals working with me and collaborating with me. I am well aware of their expertise and I know how to best utilize their skills.”

Ujjwal Neogi, who works at Karolinska Institutet, spearheaded the bioinformatics portion of the research. Ujjwal also helped in conceptualizing the idea of exploring already existing drugs to treat COVID-19. This work involved analyzing genetic code of the viruses, binding of the drugs with the target, and analyzing sequences of DNA, RNA, or protein to identify regions of similarity to find the most unchanging, widespread target for using a drug. This is important work since the smallest of differences in nucleotide sequence can result in mutations that would render these proposed COVID-19 treatments ineffective. Neogi was assisted with these tasks by Kyle Hill at the Bond LSC.

Anoop Ambikan (at Karolinska Institute) used R, a statistical computing and graphics program, to help put together the models and graphics behind this research. Xiao Heng, a member of the faculty at MU, used her expertise in biochemistry to help Singh conceptualize the research trajectory. Thomas Quinn, director of MU’s Molecular Interactions Core in the Bond LSC, helped with editing and advising throughout the process. Siddappa Byrareddy (University of Nebraska Medical Center, Omaha, Nebraska) brought previous experience with the topic of treating SARS, a form of coronavirus. Anders Sönnerborg, Singh’s longtime collaborator at Karolinska, provided funding for this work and is the one who takes the drugs to the clinic if they demonstrate potential. His involvement was important from the start of the process. Stefan Sarafianos, a former Bond LSC investigator and current collaborator had engaged with Singh in similar viral research in the past, and he imparted a lot of knowledge to Singh that enabled this research.

Taking a deeper look at potential drugs in an analytical way like this contributes to the University of Missouri System’s NextGen Precision Health Initiative. The NextGen Initiative aims to improve large-scale interdisciplinary collaboration in pursuit of life-changing precision health advancements and research.

While Singh concedes that none of his team’s work constitutes a guaranteed effective form of treatment against the virus, he feels that researchers have an obligation to continue working on a cure, and should not accept the status quo of hundreds of thousands of deaths globally. He also makes clear that for now this is all dry lab work. But plans are already in place to test these drugs in the wet lab for the validation once the appropriate protocols are established. Funding from the Karolinska Institute and the submission of two recent COVID related VA grant applications with Drs. Deutscher and Whaley-Connell will support compound validation and additional novel compound discovery and characterization.

“These treatments, if they turn out to be effective, all have limitations,” he admitted. “But, in the midst of a global pandemic, they are worth taking a deeper look at, because we have reason to believe, based on our research, that all of these drugs could potentially be effective in treating COVID-19.”

Kamlendra Singh is Assistant Director of the MU Molecular Interactions Core and an MU Associate Research Professor of Veterinary Pathology in the Collage of Veterinary Medicine (as of May 1, 2020).

Read more details about this research in “Feasibility of Known RNA Polymerase Inhibitors as Anti-SARS-CoV-2 Drugs,” published April 26 in the journal Pathogens.

The Lab in Time of COVID-19

April 29, 2020 By Lauren Hines in Research Tags: COVID-19, Marc Johnson

The main halls of Bond LSC are empty due to researchers being told to work from home. | photo by Roger Meissen, Bond LSC.

By Lauren Hines | Bond LSC

On an average day, you can find post doctorate Norman Best surrounded by corn in the greenhouse or at his bench in the McSteen lab doing molecular work. However, since Columbia and state leaders issued a stay-at-home order on March 25 to prevent the spread of COVID-19, this means Bond LSC is mostly empty and researchers like Best are at home writing.

“It’s definitely made me appreciate what I had before,” Best said.

Coronaviruses are a family of viruses that can cause respiratory illness in humans. They’re found circulating among animals, and then passed to humans. While the world has seen dangerous coronavirus outbreaks including severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome coronavirus (MERS) in 2012, the 2019 emergence of COVID-19 has spread much more quickly.

According to the Centers for Disease Control and Prevention, COVID-19 is spread through respiratory droplets produced when an infected person coughs, sneezes or talks. Staying at home and avoiding contact with others will help prevent the spread.

Most researchers are working from a distance, like Best who is writing a paper on how the plant hormones auxin and brassinosteroid affect lateral meristem growth. However, some are deemed essential whether it’s to water plants, finish crucial experiments or study COVID-19 itself.

Marc Johnson, professor of molecular microbiology and immunology, is currently studying glycoproteins which are proteins on the surface of viruses that dictate what cell they’re going to infect. Even though Johnson usually works on HIV, he’s shifting his focus to COVID-19 and its glycoproteins called, spike.

Johnson is taking other viruses and replacing their glycoproteins with COVID-19 spike proteins to basically create a safe version of our current coronavirus. This will allow him to do multiple tests to try to inhibit viral entry.

In addition, these experiments can also test the effectiveness of antibodies. Recovered patients are donating their plasma — blood without red blood cells and just antibodies — to transfer their coronavirus-fighting antibodies to other patients.

Marc Johnson observes cells modified with CRISPR under the microscope. | photo by Jennifer Lu, Bond LSC.

“Of course, if you take plasma from a patient, you want to make sure that there are the antibodies you want in there, so that’s where my [experiment] would come into play to check whether there’s a high level of neutralizing antibodies in their serum,” Johnson said. “If there is, then you know it’s good for injecting. It might be helpful for the patient.”

For those who aren’t working on COVID-19, the interruption has some feeling frustrated.

When Best was in the lab, he was doing molecular work on creating a CRISPR construct. CRISPR is a method of editing genes, essentially splicing DNA into a cell. Now, it’s sitting in the freezer half done.

“I’m working on finishing up a few publications that I’ve had data for that I’ve actually

not been able to analyze before,” Best said. “I had not taken the time to analyze as much as I have now because I am sitting all day on the computer…However, there are still a few things left to do in the lab that have been delayed because of quarantining.”

Jean Camden, senior research associate in the Weisman lab, goes into Bond LSC once a week to check on the mouse breeding colony in addition to working from home.

“For us, the timing was good,” Camden said. “We had just finished some large experiments, and we are now writing, all of us. We have plenty of work to do at home.”

For many researchers, as Camden describes, writing papers is one of the last tasks to do.

“Now there’s no excuse,” Camden said. There’s nothing else to do but write.”

However, even the mounds of data researchers have been sitting on will eventually run out.

“If [the end of social distancing] doesn’t happen within the next two or three weeks, then we will be getting behind on getting experiments done,” Camden said.

So far, MU has moved in-person summer classes online, but is hopeful to re-open campus in the fall under a “new normal.”

“[The end of social distancing] should depend on our preparedness and the resources because one of the reasons why I think we shut down is that we weren’t ready to cater for all the people that were going to be sick, and so the best option was to prevent it,” said Kwaku Tawiah, fifth year graduate student who studies Ebola in the Donald Burke lab. “I don’t know when normal life can return as we knew it before.”

Even though there’s a lot of uncertainty of what’s ahead, Bond LSC researchers are learning to adapt and are continuing their research.

“It is very fortunate that I have been able to work at home and keep my job,” Camden said. “A lot of people here in Columbia have been laid off, and I feel bad for the terrible things that have happened. So, I appreciate the position that I’m in.”

At the moment, Best is still sitting at home with his dog analyzing data and writing. He expects his paper on lateral suppressor1 to be published soon among many others in the works.

“I think we’re all ready to get back to normal life,” Camden said.

Influenza & COVID-19 Research: A Campus-wide Effort

April 29, 2020 By Becca Wolf in Research Tags: COVID-19, Henry Wan, influenza

By Becca Wolf | Bond LSC

With shelter in place orders being extended throughout the country and events being canceled, COVID-19 is a pressing issue, and influenza researchers at MU have been pivoting recently to begin studying the virus.

Henry Wan, an influenza researcher and Bond LSC principal investigator, is planning on expanding his work to start looking at COVID-19 along with a team of epidemiologists, anthropologists, engineers, and more at MU. While influenza and COVID-19 are not the same virus, both are infectious respiratory illnesses transmitted through similar ways.

COVID-19

Wan has spent years investigating the workings of influenza, so as the COVID-19 pandemic has played out he has been keeping an eye on its developments. He explained COVID-19 is “being incorporated into my study, in that human cohort, to study and monitor the disease that is going on here. We have established the diagnostic capacity in the lab for COVID-19 but I haven’t tested any samples yet,” he said as of March 18.

A few weeks ago, there was an online meeting of virus researchers at MU to discuss research efforts to combat COVID-19 and what their labs bring to the table. One idea they came up with is to have a cohort in Columbia, that would provide materials such as blood samples over time to track not only the spread of influenza and COVID-19, but vaccine and medication effectiveness. Jane McElroy, an epidemiologist in the MU school of medicine said, “Right now there’s the flu vaccine, so we want to get serum samples four times a year from community members, around vaccine times, and then a couple of times throughout the year to just see what their antibodies look like.”

“Once we have a COVID-19 vaccine, the participants in a cohort could help us by letting us see how their body’s immune functions are maintained with the vaccination,” she said.

This way, MU researchers would not only be getting information on influenza in Columbia but also COVID-19.

Lisa Sattenspiel, professor and chair of anthropology at MU, is also starting a project that is based on her research on the 1918 influenza epidemic. She is comparing the patterns from 1918 to what is going on with the current pandemic and looking at social, economic, and behavioral data to track the spread. “We’re starting this project now,” she said and a National Science Foundation grant proposal has recently been submitted for funding this idea.

Though a very serious and quick-moving situation, Wan and his collaborators are coming up with ideas to understand COVID-19. Not much is known yet about the virus, but they are doing their best to change that.

MU Collaborators

Wan cannot complete this research on his own. Along with students in his lab, he has already collaborated with more than 15 people throughout MU.

“I really enjoy collaboration, everyone is very passionate,” he said, “I think it is very important.”

Everyone brings a unique perspective and expertise to the team which leads to more breakthroughs.

McElroy has connections in the medical field that help Wan obtain samples from people who have influenza symptoms and, in the future, potentially people with COVID-19 symptoms as well. Working with her colleague, Dr. Shamita Misra, medical director of Mizzou Quick Care Clinics located in Columbia Hy-Vee stores, health care providers gather these samples from community members. Extending this work, McElroy has begun working with Dr. Christopher Sampson, a University of Missouri Health System emergency room physician, to identify and gather blood samples from patients with COVID-19.

By using samples from the community, Wan is able to track trends throughout Columbia and use that information to find ways to make the community healthier.

Another person Wan has collaborated with is Sattenspiel, who has been conducting influenza research for more than 25 years.

Sattenspiel tracks how influenza spreads throughout communities with computerized models of towns that simulate potential outbreaks. Having this knowledge gives Wan and his team a better idea of the rate influenza spreads and how to stop it.

Sattenspiel explained, “We are working on designing models that can deal with the entire life cycle of a virus and what goes on at the community level, how it gets transmitted within communities, how it gets transmitted within households, and what happens inside the human body. Ultimately, the goal is to look at different strategies for controlling it.”

With this model, she can test preventative strategies and see their effects.

“So things like vaccinations, if the vaccination works in a certain way, what’s its impact going to be, not only for the individual who was vaccinated but for the community in which they live?” Sattenspiel said.

Another preventative strategy they are looking at is social distancing, which has become relevant and especially effective recently with the COVID-19 pandemic. Through these collaborations, Wan is able to get a well-rounded view of influenza in order to create effective vaccines. He also hopes the addition of the new Next Gen Precision Medicine Institute will expand his research even further.

Wan’s Influenza Research

Arriving at Bond LSC last summer, Wan hit the ground running. He already has several grants and collaborators working on projects to improve the flu vaccine and figure out how influenza spreads in addition to his other work.

“We mainly focus on two aspects,” Wan said, “On one side I’ve been mainly focused on the influenza vaccine and the other aspect on influenza risk assessment.”

As a result, Wan’s lab looks at many factors such as, why the flu vaccine does not work, how to get a better flu vaccine, and which flu virus is more dangerous to humans, among others.

To test this, Wan gathers swab samples from people who have influenza much like how COVID-19 samples are collected.

“From the swab, we look at the virus whether it matches any flu vaccines,” he said. Wan and his graduate students and other senior lab members then look at this data and interpret it to come up with a solution.

Wan recently received a $3.65 million research project grant from the National Institute of Health (NIH) to determine if the number of vaccines a person has affects the number of times they will be infected with influenza. He said getting a flu vaccine results in “A lot of heterogeneity in our immune profile, affecting the vaccine.”

Wan and his team are curious if these vaccines build off each other and what the yearly effect of getting a flu shot is on the body. By understanding this, he will be able to come up with a way to improve the vaccination program, making it stronger.

In addition to this grant, Wan’s two other grants focus on predicting the influenza virus. Using artificial intelligence (AI), machine learning technology, and sequencing techniques, he looks at how the virus mutates and escapes the immunity in human populations. With this information, scientists are informed on how to make an effective vaccine, especially with new strands of influenza.

The Future

Just because COVID-19 is currently the world’s main focus, does not mean it’s the only virus in town. People still get sick from influenza annually, so Wan and his collaborators plan to continue their research on the spread of influenza and improving vaccines.

“The resources are really focused on coronaviruses because of what’s happening right now, but influenza is not going to go away either,” said McElroy, “Lots of people also die from influenza every year so we know that it is also important.”

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