This exciting ERC funded project in the Courtney Lab focuses on virus-host interactions and RNA modifications (epitranscriptomics) to uncover novel pathways hijacked by influenza A viruses (IAVs) that allow viral RNAs to avoid detection by innate immune sensors, be trafficked from the nuclear replication centres to the cellular membrane and be efficiently packaged into virions.
We are looking for an enthusiastic student who has a real interest in molecular virology to work on this potentially ground-breaking work and really delve into the many roles RNA modifications may play in the regulation of influenza negative strand viral RNAs (vRNAs). We think that vRNA modifications will have quite distinctive roles from those on mRNAs, due to their involvement in distinct processes. Therefore, the study of vRNA epitranscriptomics will answer important questions most likely entirely unique to IAV. Elucidating these novel roles will be a significant advancement in our understanding of the IAV replication cycle.
Initially, common mRNA modifications will be mapped on IAV vRNAs in infected eukaryotic cells. We will use this mapping data to rescue and characterise hypo-modified viral mutants. We will evaluate viral fitness before determining whether characteristics such as trafficking or packaging are altered upon loss of modifications. Visualisation of vRNAs in vitro will allow us to ascertain if hypo-modified vRNAs accumulate at cell structures, while packaging efficiency will be evaluated through ultracentrifuge purification of IAV virions. RNA affinity purification will then be performed to identify RNA-binding proteins (RBPs) that associate with specific modified regions, and validated by CLIP-seq. We will also seek to identify RBPs blocked from binding vRNAs by the presence of RNA modifications, including innate immune sensors. We will determine the phenotypic effect these validated candidate RBPs have on IAV pathogenesis, and the mechanisms behind these effects, using standard molecular methods.
This project would be ideal for a student with at least a BSc Upper Second in Biological or Life Sciences (especially virology, biochemistry, biomedical or bioengineering).
Please apply at https://www.qub.ac.uk/courses/postgraduate-research/phd-opportunities/elucidating-the-role-of-rna-modifications-on-negative-strand-influenza-a-rnas-during-the-viral-replication-cycle.html
Feel free to contact Dr Courtney at [Email Address Removed] if you have any questions regarding this project.
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