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USask research explores role of microproteins in virus replication

$1.2 million in funding through Canadian Institutes of Health Research applied to the project.
anil_kumar
Dr. Anil Kumar (PhD) with the Department of Biochemistry, Microbiology and Immunology in the College of Medicine.

SASKATOON — Researchers are still discovering more about the fundamental building blocks of human cells and a University of Saskatchewan (USask)-led research project is exploring microproteins and their role in defending against viruses.

Dr. Anil Kumar (PhD) with the Department of Biochemistry, Microbiology and Immunology in the College of Medicine received $1.2 million through the Canadian Institutes of Health Research (CIHR) Fall 2024 Project Grant competition to investigate the mechanisms behind how microproteins – a recently discovered group of small proteins in the cell – help spread enteroviruses and how the body uses this group of protein to defend against virus infections.

Kumar highlighted that the human body was previously understood to produce roughly 20,000 different proteins and in the last decade scientists have identified around 7,000 additional smaller proteins – termed microproteins – in human cells. These microproteins appear to play roles in many basic cellular functions, including the response to viral infections.

“For microproteins, most of their functions in the cells are still unknown,” he said. “When we work on these microproteins and find some of them having a role in virus infections, we also discover their cellular roles, like what kind of pathways they regulate.”

Kumar’s research is delving into the cellular mechanisms behind how exactly different microproteins affect viral replication, and through that research understand more about the function of those 7,000 microproteins in the human body.

The researchers use gene editing tools like CRISPR technology to either “knock out” or increase the expression of different microproteins to identify which ones help or hinder virus replication. Kumar’s earlier research, supported by a College of Medicine Research and Development (COMRAD) grant, showed that increasing the expression of certain microproteins in cells caused virus replication to go down by more than 90 per cent.

“The virus life cycle is intimately linked with the biology of the cell,” Kumar said. “When microproteins came to light, there was nothing known about how they affect virus replication, so that is a large gap in our knowledge on their biology.”

Kumar and his team are focusing on enterovirus D68 (EV-D68), a once-rare virus that has seen a resurgence in the last decades across the globe. The virus causes acute flaccid myelitis, a polio-like illness characterized by muscular and respiratory paralysis especially in children.

EV-D68 was chosen as a focus due to the modern health risks it poses and because there is already an established research program on this virus in Kumar’s lab that was supported by funding from Saskatchewan Health Research Foundation. Kumar said they plan to expand their study to other important human viruses like coronaviruses and equine encephalitis viruses that are relevant in the Canadian context.

He hopes that the CIHR funding will help the research team develop a comprehensive set of microprotein research tools to study their role in virus infections and potentially open new avenues for drug development for treating enteroviruses. Kumar also noted that the research tools developed in his lab could have wide-reaching benefits for other colleagues in medicinal and biochemical fields at USask who are interested in studying how microproteins affect their realm of research.

Kumar said the novelty of this research field is exciting as a scientist, and said he believed this work will have large implications for our understanding of how the cell and how infections function, or even why some viruses cause severe infection in some people more than others.

“We could learn something major about cell biology and virus infections by looking into this,” he said. “It is a wholly unexplored field ... Some of those unanswered questions about what’s going on inside the cell during virus infections, I hope to get answered.” 

Other CIHR Fall 2024 Project Grant recipients at USask
  • Linda Chelico (PhD), College of Medicine – Role of APOBEC3 single-stranded DNA cytosine deaminases in breast cancer – $100,000 for a one-year project
  • Steven Machtaler (PhD), College of Medicine – Ultrasound molecular imaging of intestinal stenosis: Developing a contrast agent to distinguish between inflammatory and fibrotic strictures in patients with inflammatory bowel disease – $875,925 for a five-year project

— Submitted by USask Media Relations

 

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