SUNY Oswego students, faculty and recent alumni were part of a research team that spans many institutions and disciplines to research the COVID-19 pandemic resulting from the SARS-CoV-2 virus.

SUNY Oswego students Emily Fingar, Michael Kirsch and Charlotte Labrie-Cleary and recent graduates Ali Khan and Santiago Soto joined Julia Koeppe of the chemistry faculty for the weeklong bootcamp hosted by the Institute for Quantitative Biomedicine at Rutgers University this summer.

Other institutions in Oswego’s group included Rochester Institute of Technology, Ursinus College, Hope College, Grand View University and Xavier University. The goal was to bring together teams of interdisciplinary researchers with complementary skills and interests to investigate the virus. Carried out completely remotely, participants interacted with experts and learned how to use various bioinformatics tools to answer pertinent research questions.

Research focused on the SARS-CoV-2 main protease (an enzyme that breaks down proteins into smaller units), which is essential for viral activity and a promising drug target. By understanding the differences in this protease resulting from the rapid evolution, researchers can move closer to developing an antiviral medicine to help COVID-19 patients, Koeppe said.

“Students learned to work remotely (in Zoom and Zoom breakout rooms) with a group of their peers and a faculty mentor to study the structure and function of the main protease from the virus,” Koeppe said. Students learned about computer programs used to view macromolecules such as proteins and enzymes; key principles of bioinformatics, such as sequence alignments that can show the evolution of proteins; and computer programs that model protein folding to determine three-dimensional structures.

“At the end of the boot camp, all of the students gave a short presentation with their group members on some specific questions that they explored when looking at changes in the amino acid sequence of the SARS-CoV-2 protease and how they expected these changes would or would not affect the function of the protease,” Koeppe said.

Preparing young researchers

Khan, a May graduate who is starting Ph.D. work in cancer biology at the University of Iowa’s Carver Medical School, worked in a team with two other students and Koeppe.

“We were given daily tasks in which we used various structural visualizing tools to understand different mutations of coronavirus with respect to bond length, change in heat energy, etc.,” Khan said. “There were a couple of mutations assigned per group and we had to analyze those and came up with a conclusion. We then gave a mini-presentation at the end of the week for our group about our findings.”

Khan said the knowledge and interactions all were fruitful for his future plans.

“This Bootcamp taught me how to interface with a scientist in a different field,” Khan said. “I also got an opportunity to attend various lectures which taught me the importance of research and how impactful research can be. I was also able to learn how to use visualization softwares and python programming language which will definitely come in handy in my Ph.D.”

For Santiago Soto, who earned his biology degree in May and is already working in the field professionally as a clinical laboratory technologist with Acutis Diagnostics, the bootcamp helped with his important everyday work with live SARS-CoV-2 samples.  

“I really enjoyed the opportunity to observe the mutation and evolution process of SARS-CoV-2s over the past six months and its main protease Nsp5 while comparing it to the original viral isolate to 161 unique sequence/structure variants,” Soto said. “This was done by analyzing amino acid sequences using 3D atomic level structures using several bioinformatic tools.” The research found Nsp5 could be a promising drug target for vaccine development, he added.

“This bootcamp allowed me to better understand the use of bioinformatics/biostatistics,” Soto noted. “It’s the base principle on being able to make identifications on the genetic basis of diseases, their desirable properties and unique adaptations. I would like to pursue sometime in the future a graduate degree and career in epidemiology, biomedical engineering or genetics, where the use of bioinformatics is constantly being used to assist in progression.”

A member of Koeppe's research team, senior biology and health science major Emily Fingar was “immediately interested” when Koeppe reached out with the opportunity. She learned Foldit, PyRosetta, and Mol visualization software programs “so that we could take our assigned mutants, where we had the DNA sequence but not necessarily a structure, and force those mutations into the known protease structure,” she said. 

“My team specifically was assigned 11 mutations in the SARS-CoV-2 main protease to characterize,” Fingar said. “Our goal was to model, using these programs, how each of the assigned mutations of the SARS-CoV-2 main protease might be changing at the protein level as well as the stability of that protein. We also used this data to examine if there are regions in the protein structure that are mutating more often than other regions.”

Fingar said the bootcamp helped her continue to broaden computational skills for research. “I'll be the first to admit I'm not the best with computers,” Fingar said. “This opportunity has shown me that I am capable of learning and effectively utilizing them in a meaningful way that is relevant to my research. My next challenge will be to tackle the statistical programming language R.”

‘Exhilarating’ pace

Senior biochemistry major Charlotte Labrie-Cleary found the opportunity to work in remote teams and gain experience relevant to research were key takeaways.

“I learned how to use incredibly powerful bioinformatic tools that I hope to learn more about in the future,” Labrie-Cleary said. “I learned about the evolution of viruses with a focus on coronaviruses. We learned in depth about the SARS-CoV-2 main protease as well as its spike protein and why they're important. We learned about testing techniques for COVID-19 and how they work.”

For Labrie-Cleary. learning so much at a fast pace “was exhilarating and I feel lucky to have been able to participate,” she said. “It has shed light into the world of bioinformatics, which is something I have always been super interested in. This experience will give me a head start when considering graduate programs, and it excites me to learn more about it. As an undergraduate, I am fortunate to have been offered such a valuable experience, as many students at our level are not offered such during undergraduate studies.” 

Senior biochemistry major Michael Kirsch appreciated learning about topics such as “the evolution of RNA viruses, development of testing for COVID-19, what parts of COVID-19 might be the best to target with medicines that are being developed to treat it, and how phylogenetic trees can be used to help piece together when different mutations in a virus branch off from one another,” he said.

His team used Mol and Foldit to examine the protein 6YB7, the COVID-19 main protease, which could lead to research on “what affects its ability to do its job as a protease, and future research can then be done on how to disrupt this protein from doing its job,” Kirsch said.

Virology, the study of viruses, is among the future fields Kirsch is considering, and the bootcamp has further encouraged him. “I now know how to use several new programs to visualize or otherwise analyze proteins, which will be useful in my last semester at Oswego, as the research I do with Dr. Koeppe is focused on determining the function of protein 3DL1,” he said. “Being able to better visualize it can only help my research efforts, which I'm excited about.”

The bootcamp will allow Koeppe to provide better lab experiences and topical opportunities for her students.

“I am currently modifying some of the bootcamp materials to use them as online lab experiments in our biochemistry lab courses for the fall semester, and I will also create a unit on the novel coronavirus and the main protease for my master’s-level enzymes course for the fall semester,” Koeppe noted. “Students who are interested in further study will be welcome to join my research group where they can begin with computational experiments to study the viral proteins with a goal of identifying a possible drug target.”

Koeppe and chemistry faculty member Kestutis Bendinskas have been using tools developed at the boot camp to design experiments for studying SARS-CoV-2 in their biochemistry lab courses.

The experience can help Koeppe develop “a unit on computational software for protein folding into our biochemistry lab curriculum that focuses on enzymes of unknown function,” she said. “The software we used for protein folding in the bootcamp was new to all of us, and we think it will be a good addition to what we've already been using in the lab.”