Suppes, Davis (MU-Student)

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Two SARS-CoV-2 strains cause independent infections only 19 days apart

August 5, 2021 By Suppes, Davis (MU-Student) in Research Tags: COVID-19, Mizzou Research

Increasing detection of reinfections and rediscovering brand new infections within days raises concerns for herd immunity and the durability of vaccine efficacy.

Cynthia Tang working to figure out how COVID-19 reinfections can bring us answers on how the virus is developing at Bond LSC. | photo by Davis Suppes, Bond LSC

By Davis Suppes | Bond LSC

Like many viruses, SARS-CoV-2 continues to develop and evolve with time. As the virus evolves it becomes more infectious and can produce worse symptoms and a higher fatality rate. While more people have been infected, we also learn more about it, including how different variants of the same virus can reinfect someone who already had SARS-CoV-2.

In a recent study led by Cynthia Tang, an MD-PhD student at the University of Missouri (MU) School of Medicine and Institute for Data Science and Informatics, her lab was able to identify a patient who got reinfected with a different strain of SARS-CoV-2 just 19 days after their initial infection. Her Systems Biology Laboratory is headed by Principal Investigator, Dr. Henry Wan, who directs the MU Center for Influenza and Emerging infectious Diseases.

“We found a case of reinfection that occurred during a shorter window of time than what we see in the current US Centers for Disease Control and Prevention (CDC) guidelines,” Tang said, “so we may be missing a subset of those reinfection cases.”

In October 2020, the CDC published investigative criteria for suspected SARS-CoV-2 reinfections. These criteria included: any individuals testing positive over 90 days after their first laboratory-confirmed SARS-CoV-2 infection, or symptomatic individuals testing positive 45–89 days after initial infection with paired respiratory specimens.

For this patient, nineteen days following her initial positive test in March of 2020, she returned for another SARS-CoV-2 test due to return-to-work requirements. Despite her symptoms fading to encompass only productive cough and fatigue she tested positive again. She continued to experience persistent cough, fatigue, and difficulty breathing until 55 days after her initial positive test.

Tang showed that the two samples contained two infectious variants of SARS-CoV-2 viruses. No diverse polymorphisms, or a mixture of different viruses, were identified among the sequences of the viruses from each clinical sample, suggesting true reinfection rather than a coinfection. One good news is that this case also suggests that reinfections may not be worse than the prior infection.

The CDC has encouraged symptom-based strategies for ending isolation rather than viral retesting for asymptomatic individuals or for individuals without new symptoms during 90 days after illness onset due to findings that detectable but noninfectious SARS-CoV-2 RNA can persist in respiratory samples. This means that even if you don’t exhibit symptoms there could still be traces of SARS-CoV-2 in your system, and those traces could be from an original infection or a reinfection.

This study suggested that reinfection could pose a challenge to infection control, especially as the Delta variants are surging around and new variants continue to emerge.

“People showing influenza-like illnesses are recommended to isolate themselves for ten days or wait for their symptoms to go away. We may not be catching cases where individuals contract another COVID-19 infection within a short amount of time,” Tang said.

“The COVID-19 vaccination has been proven to be effective in reducing the chances for people to become infected and reinfected”, Tang added.

This research was published in the Journal of Medical Virology in June 2021.

Bringing Protection Back in Line

July 23, 2021 By Suppes, Davis (MU-Student) in Research Tags: Mizzou Research

Research refines platform to address immune disorders

Dr. Esma Yolcu and Dr. Haval Shirwan, Co-pioneers of ProtEx technology

By Davis Suppes | Bond LSC

The things that protect you can also cause the most harm. That’s especially true when it comes to your immune system, which protects you against infections, but is also responsible for a host of diseases, including autoimmune disorders, such as type 1 diabetes.

More than 1.4 million Americans suffer from the self-harming condition of diabetes without an effective cure, but researchers Haval Shirwan and Esma Yolcu may have the answer.

The pair tackle the problem of diabetes and other autoimmune disorders by targeting the component of the immune system that does harm for modulation. DNA-based gene therapy has traditionally been used as a scheme to modulate the immune system.

“DNA-based gene therapy is a complicated, exhaustive and expensive technology,” said Shirwan, a NextGen Precision Health researcher at the University of Missouri and a professor in the Department of Child Health and Molecular Microbiology and Immunology at the School of Medicine. “We wanted to see if there was a more efficient and practical way to do immunomodulation.”

For conditions like Type 1 diabetes, where the immune system misfires and destroy beta cells producing insulin, they target to replace defective islets with healthy ones from another individual. Insulin is an important hormone that plays a role in regulating your blood sugar level. A major hurdle for islet transplantation is the immune rejection.

Shirwan and Yolcu co-pioneered ProtEx™, a proprietary platform that allows for generation of novel recombinant immune ligands and their positional display as single agents or in combination on biological surfaces, such as islets. This is a practical and safe alternative to gene therapy for localized immunomodulation.

In traditional methods of gene therapy, DNA must first be introduced into the cell, but ProtEx technology bypasses that step. Sticking the protein directly on the cell surface for immunotherapy via a test tube allows for a safer, more effective method than gene therapy. Islets engineered to stick on their surface proteins evade rejection by the immune system.

Shirwan’s translational research program’s goal is to develop safe and practical immunomodulatory approaches with applications to transplantation, autoimmunity, cancer, and infections. On the cancer side, Shirwan and Yolcu team has shown that the immune system of a healthy individual can be trained to surveillance the body for cells that may transform into cancer and eliminate them before cancer takes hold. “This is an exciting finding that has not been reported in the literature and sets the stage for

Shirwan’s focus of learning about the immune system and improving it came to him very early when he was a virologist for University of California, Santa Barbara. He developed an interest in immunology and wanted to learn more about immune defense mechanisms. Before bringing his talents to Mizzou he also spent time working at the California Institute of Technology, Allegheny University of the Health Sciences, University of Louisville, and Cedars-Sinai Medical Center.

He believes preventing these cancers and infections is the route we should be aiming toward, rather than trying to find new ways to treat them after they have already damaged the body to an extent.

“Things like cancer are so effective and harmful because they use the same mechanism as the immune system to evade it,” Dr. Shirwan said, “Just like how a runner can build muscle memory for running, our immune system can learn and build up a memory of these pathogens and infections to create a more effective response.”

“This is just the tip of the iceberg,” Dr. Shirwan said, “I am very excited to continue expanding on what our immune system is capable of.”

This type of research contributes to the University of Missouri System’s NextGen Precision Health focus. The NextGen Initiative unites scientists, government and industry leaders with innovators from across the system’s four research universities in pursuit of life-changing precision health advancements.

Dr. Shirwan and his team are moving to the new NextGen building on Mizzou’s campus in mid-September. He is very thankful for getting the opportunity to work in these facilities with these people, and he is excited for the next step of their research.

Shirwan believes we have only scratched the surface of what our immune system is capable of. Our immune system may not always know what is good and bad for itself but one thing is for sure, Dr. Haval Shirwan is good for it.

A scientist steps away from the bench

July 1, 2021 By Suppes, Davis (MU-Student) in Faces of Science Tags: Mizzou Research

After 40 years of hard work, it is finally time for David Pintel to pass the torch.

By Davis Suppes| Bond LSC

David Pintel is hanging up his lab coat after 40 years.

“It’s been an honor to be able to do my work at the University of Missouri. I’ve had a great group of colleagues both here and at the medical school,” Pintel said.

The Bond LSC virologist retired July 1 after a storied career. He spent 20 years at the School of Medicine before joining Bond LSC upon its completion more than 15 years ago.

Since then he has aimed to better understand the interaction between viruses and host cells. Pintel specialized in the study of parvoviruses, the smallest of all DNA viruses that infect vertebrates. In addition, the parvovirus adeno-associated virus (AAV) has been developed as a promising gene therapy vehicle.

On his last official day in his office Pintel was busy still packing up old memories while taking everything in.

“I’ve had tremendous students and tremendous colleagues, you know they were the important parts of my career,” Pintel said, “Going through all the old memories, you know, it’s gonna take a little while”

Pintel is a Curators’ Distinguished Professor as well as a Dr. R. Phillip and Diane Acuff Endowed Professor in Medical Research Molecular Microbiology and Immunology. He reflected on fond memories of his work here, but when asked what his favorite memory was his answer was the same, working with all of these people.

“It’s an emotional end, when you do something every day of your life for 40 years,” Pintel said. “I’m so thankful and grateful for the people that have worked with me, people that have been my friends here and allowed me to have a successful career.”

The future for Pintel will come in due time, but for now he is in no hurry and plans to enjoy some time off.

“To be determined,” Pintel said, “I think I will decompress for a while before I make any decisions on the next step.”

#IAmScience Lyndon Coghill

June 24, 2021 By Suppes, Davis (MU-Student) in #IAmScience Tags: bioinformatics, Mizzou Research

Lyndon Coghill is the new Director of the Bioinformatics and Analytics Core, and he is already making big moves at Mizzou.

By Davis Suppes | Bond LSC

Lyndon Coghill’s official title may be Director of Informatics for the Bioinformatics and Analytics Core, but his job branches out much wider than just a single label. Even as an undergrad, Coghill wore many different hats.

“I was incredibly excited about the way that the MU Office of Research and Economic Development recruited me,” Coghill said, “With these types of processes you can get an idea as to whether or not an institution is actually committed and excited about building something out.”

With his experience and range of expertise, Coghill was an easy choice for Mizzou to fill the role of Director of the Bioinformatics and Analytics Core located at Bond Life Sciences Center.

Before he achieved his doctorate in biology, he completed his undergraduate degree in zoology with minors in microbiology and geology at Western Illinois University. For his dissertation, the research he conducted was focused heavily on evolutionary genomics. Simply put, he wanted to know how changes in the genome lead to changes in a physical organism that allow them to adapt better to different environments and conditions.

With his doctorate in biology, he would go on to his first postdoc at The Field Museum of Natural History in Chicago in 2013, and then on to Louisiana State University where he began his role as a senior post doctorate in 2015. He continued to diversify his portfolio there working with the department of biology, focusing on computational biology. He was then promoted to research data scientist which had him take on an even more computationally heavy role. With this, he was able to help biologists learn how to talk to computer scientists, and assist them with building collaborative programs together..

As director, Coghill’s mission is to provide bioinformatics and data science support to all researchers across the UM system. He is creating a central hub where faculty who want to conduct domain- specific biological or life sciences-related research that is computationally heavy can get the help they need to come up with solutions. He does this by helping researchers wrangle incredibly large datasets and by helping them understand what that data is telling them from an information perspective in a meaningful way.

Coghill mentioned how interim Vice Chancellor of Research and Economic Development Thomas Spencer also made a personal effort to make sure Coghill understood his vision going forward on campus “and for me that was enough of a selling point that I wanted to be a part of that,” Coghill said.

In addition to the thorough recruitment process, Mizzou’s facilities and access were other huge factors that Coghill was looking forward to once he got here. With a hospital, vet school and productive biology program all on the same campus instead of in different cities, Mizzou offers a unique opportunity to build the integrated program all in one place.

“We’re trying to reach out to every department on campus to build these relationships because you can’t have true integration of ideas and solutions if you don’t talk to everyone who might be a benefactor or have knowledge about that,” Coghill said.

Coghill believes that to create a phenomenal translational research program, this core must interact with all these programs so that experts of different fields can come together to collaborate.

“Informatics research, especially bioinformatics is a program that really forces you to keep one foot in both worlds of computer science and biology, and there’s a limited number of people who do that kind of work,” Coghill said, “I think that was one of the big pushes for getting my experience here for this position, to bring in somebody who could bring these programs together and integrate across all these different fields.”

Coghill is excited to be working with the variety of researchers and programs across the MU campus and UM System, and learning from them at the same time.

“We may not know their biological system as well as they do and we may not know the high performance computing system as well as a full-time systems administrator, but we know enough of both that we can communicate with both teams and make sure that we can help get the researchers from the starting point to a meaningful result,” Coghill said.

Their goal is to provide Mizzou and sister campuses with research support allowing faculty to build translational research programs using computing power and informatics. This core brings new opportunities for Mizzou students as well.

“We’re going to have programs for students that can rotate through as part of the Informatics and Data Science Institute,” Coghill said.

This means that students who are interested in research fields can get direct experience related to career possibilities outside of Mizzou and academics by working in this program.

“Students can come to us and learn basic coding skills, learn informatics and bioinformatics, and that will help them build a skillset that will make them quite employable,” Coghill said.

Between helping researchers in their labs and analyzing quantities of data they are gathering for the first time, Coghill has a variety of jobs he has to understand and execute.

“So, I am the guy who wears a lot of different hats and allows these researchers from different domains to talk to each other,” Coghill said. “We’re trying to help them get to the point where their work could be as big as they want.”

Mizzou and Coghill know that there is no way to push modern research without computing, especially at the scale research is done today.

It would be extremely rare for someone who has a doctorate and spent their life trying to understand how one particular part of a biological process works to also have a doctorate in computer science, “That’s where we help… we’re providing researchers with the tools to do research at a scale using computing power, and asking questions that for many, might have only been dreamed about at other times in their careers,” Coghill said.