Fighting COVID-19 gives graduate students invaluable research experience

UNIVERSITY PARK, Pa. — When the COVID-19 pandemic began to sweep across the world, many researchers shifted focus to fight the virus. Penn State’s research community was no exception, and this included biomedical engineering graduate students.  

For these graduate students, their new research focus gives them not only a strong opportunity to make a real-world impact, but also an invaluable educational experience to add to their graduate school training.

Bringing the virus’ key elements into focus 

GM Jonaid, graduate research assistant in biomedical engineering, spent much of his research time prior to the pandemic studying key proteins that are related to cancer and viruses. He conducted this work in the lab of Deborah Kelly, Lloyd & Dottie Foehr Huck Chair in Molecular Biophysics, director of the Center for Structural Oncology and professor of biomedical engineering. 

“My pre-COVID-19 work is based on cryo-electron microscopy (cryo-EM),” Jonaid said. “Before COVID-19, I worked on the BRCA1 protein, p53 protein and the AAV subtype3 virus, a non-disease-causing virus that shows promise for gene therapy. BRCA1 and p53 are key proteins in human cancer and understanding these proteins is important for curing cancer.”

Jonaid’s COVID-19 research builds on what he has already learned about cryo-EM microscopy and the AAV subtype3 virus. He applies it to a specific aspect of COVID-19, nucleocapsid protein (N protein). Groups of N proteins protect the virus RNA and keep it stable inside the virus. This makes them a potential target for treatments and vaccines. 

“Most of the vaccines or drug developments focus on spike proteins (S protein) because S protein facilitates viral entry to the host,” Jonaid said. “However, N protein is highly expressed upon infection in the host cells. As a result, it triggers a high immune response. Because of its high immunogenic response, it is an ideal candidate for both vaccine and drug development.” 

Understanding the N protein’s 3D structure is vital for vaccine and drug development. The complete structure of N protein can be resolved with the help of cryo-EM microscopes, which is the goal of Jonaid’s current research. 

“My overall graduate training goal is to develop and implement computational tools or methods for biological problems/questions,” Jonaid said. “This COVID-19 research definitely helped me to become familiar with different computational tools frequently used in cryo-EM research. I am always excited to learn new tools and apply them to my research.”

Slowing the storm with cell therapy

James Coyne, a biomedical engineering graduate student, is working in the lab of Yong Wang, professor of biomedical engineering, to develop a cell therapy treatment for COVID-19. Cell therapy involves transplanting human cells to help repair or completely replace damaged tissues. For COVID-19 patients, cell therapy has the potential to prevent cytokine storms, a severe immune reaction where the immune system releases too many cytokines, message proteins that regulate immune activity, into the body. 

Cytokine storms have caused tissue damage in pandemic patients, resulting in long-term heart and lung issues. The method Coyne is working on could prevent these complications and offer a new method of treatment. 

“Our research is important because cells are like factories producing a multitude of molecules that can be used to treat complications caused by viruses like the overactivation of the immune system,” Coyne said. “This research has shown me the potential of cell therapies and I believe they will play a role in the treatment of many diseases in addition to COVID-19.”

Coyne’s previous research, which focused on the delivery of signaling molecules to tune the local microenvironment of the disease site, was helpful in his current COVID-19 research. He could take the skills and experience he acquired from delivering biological molecules to harsh tissue sites and apply it to cell delivery.

“The COVID research required me to be flexible and apply previous experience to solve a significant problem in a short amount of time,” Coyne said. “As a graduate student in drug delivery, it is essential to identify a problem and execute the appropriate steps to solve that problem. This research is a significant clinical challenge and has been an invaluable experience in my graduate training and for my future career.”

Beyond the research experience, Coyne believes he received another benefit by joining the COVID-19 battle.

“The scientific collaboration and innovation the pandemic demanded of researchers was significant, and I am happy to say I was a part of the response,” Coyne said. 

Developing a no-needle COVID-19 vaccine

Atip Lawanprasert and Andrew Simonson, graduate students in biomedical engineering, were already focused on respiratory diseases as part of their work in the lab of Scott Medina, associate professor of biomedical engineering. Once the pandemic spread, their work focused on shifting recently published research into nanoparticle gels to COVID-19 applications. 

“This ‘nanogel’ is capable of delivering drugs and other cargo, in this case genes that encode for various SARS-CoV-2 proteins, to white blood cells that specialize in propagating immune responses,” Lawanprasert said. “By delivering these genetic materials to the respiratory tract as an inhalable aerosol, we can target an immune response at the primary infection site, ultimately suppressing future infection.”

Simonson added that there are other inhalable vaccine benefits beyond effectiveness. 

“Additionally, this method is much simpler and does not require special medical training, ultimately minimizing responsibilities of medical personnel,” Simonson said. “This method is also less invasive due to avoiding the need for needles, which can often scare patients from receiving the vaccine.”

The experience gave both Simonson and Lawanprasert additional training they never expected, and both believe it will make them better biomedical engineers.

“Most of the work in Dr. Medina’s lab has been applied to cancer and bacterial pathogens, so switching gears to COVID vaccination certainly expanded my training to a new area,” Simonson said.

Lawanprasert said he learned that as a researcher, you have to adapt to new information quickly, in real time.

“One of the most important skills that we receive during this research is the ability to adapt to or learn new knowledge that is presented to us over time,” Lawanprasert said. “It is remarkable that we are still learning new things about COVID-19 even after months of doing research.”