Estelle Gamage Samaraweera
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Estelle’s research focuses on the role of the ubiquitin like protein, UFM1, in viral infections. She recently completed her Bachelor of Science Honours degree in Microbiology and Immunology at Dalhousie University in Halifax, Nova Scotia. She did her honours project in the McCormick lab, where she investigated the host UFMylation pathway during Influenza A virus infections, under the supervision of Dr. Craig McCormick. Currently, she continues to work in the McCormick lab as a Research Assistant, studying the UFMylation cascade. She will be starting a career in industry in the near future.
Investigating the host UFMylation pathway in influenza virus infection
Ubiquitin-Fold Modifier-1 (UFM1) is a Ubiquitin-like (UbL) protein that can be covalently linked to lysine residues on target proteins. This process, known as UFMylation, regulates endoplasmic reticulum (ER) quality control mechanisms and innate immune responses. Enveloped viruses, like influenza A viruses (IAVs), have complex interactions with ER proteostasis machinery. IAV encodes glycoproteins that can burden protein folding machinery and trigger ER stress. Here, we demonstrate that UFMylation regulates IAV infection. We used a CRISPR/Cas9 genome editing based approach to create human lung epithelial cell lines deficient in UFM1 or UFM1-specific cysteine protease 2 (UFSP2), required to deconjugate UFM1 from substrate proteins. Successful deletion of UFM1 and UFSP2 was demonstrated by the absence of respective protein products in cell lysates. This had the expected effect on the known UFMylation target ribosomal protein L26 (RPL26), whereby UFM1 deletion prevented RPL26 UFMylation and UFSP2 deletion caused the accumulation of high levels of UFMylated RPL26. These cell lines were infected with IAV to determine the effect of UFMylation on viral replication. UFSP2 deficiency had no effect on IAV replication and release of infectious progeny viruses. Contrastingly, UFM1 deficiency resulted in increased IAV replication at both low and high MOI infections, suggesting an antiviral effect of UFM1. Ongoing work is addressing how UFM1 deficiency affects discrete steps in viral replication, including glycoprotein processing and accumulation. We are also investigating how UFM1 regulates ER stress responses and innate immune responses in IAV infected cells. This work may help us understand how UFMylation contributes to host defense.