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Department of Pathology

 

Our Research

We are interested in the molecular biology of all sorts of RNA viruses - including both plant and animal viruses. We are especially interested in the many weird and wonderful mechanisms that RNA viruses use to express their genes, including the discovery of new 'hidden' genes in RNA virus genomes, and elucidation of novel mechanisms of regulating gene expression. Much of our work is motivated by comparative genomic analysis of virus genome sequence alignments as a route to identifying previously overlooked functional elements. Recent work has included identification of novel genes in astroviruses, enteroviruses and SARS-CoV-2, discovery and characterization of protein-stimulated ribosomal frameshifting in cardioviruses and arteriviruses and +1 frameshifting in influenza A virus, and studies of transcriptional slippage for gene expression in potyviruses. We are also interested in ribosome profiling (Ribo-seq), RNA-seq and Ribo-seq data analysis, novel virus discovery, and RNA structure and function.

Current Projects

  • RNA virus gene expression, comparative genomics and molecular biology
  • Non-canonical translation mechanisms
  • Novel virus discovery
  • Ribosome profiling
  • RNA structure and function
  • Bioinformatics

Key Publications

  • Lulla V*, Firth AE* (2020) A hidden gene in astroviruses encodes a viroporin. Nat Commun 11:4070.
  • Lulla V*, Dinan AM, Hosmillo M, Chaudhry Y, Sherry L, Irigoyen N, Nayak KM, Stonehouse NJ, Zilbauer M, Goodfellow I, Firth AE* (2019) An upstream protein-coding region in enteroviruses modulates virus infection in gut epithelial cells. Nat Micro 4:280-292.
  • Napthine S, Ling R, Finch LK, Jones JD, Bell S, Brierley I*, Firth AE* (2017) Protein-directed ribosomal frameshifting temporally regulates gene expression. Nat Commun 8:15582.
  • Irigoyen N*, Firth AE*, Jones JD, Chung BY, Siddell SG, Brierley I* (2016) High-resolution analysis of coronavirus gene expression by RNA sequencing and ribosome profiling. PLoS Pathog 12:e1005473.
  • Olspert A, Chung BY, Atkins JF, Carr JP, Firth AE* (2015) Transcriptional slippage in the positive-sense RNA virus family PotyviridaeEMBO Rep 16:995-1004.
  • Firth AE* (2014) Mapping overlapping functional elements embedded within the protein-coding regions of RNA viruses. Nucleic Acids Res 42:12425-12439.
  • Fang Y*, Treffers EE, Li Y, Tas A, Sun Z, van der Meer Y, de Ru AH, van Veelen PA, Atkins JF, Snijder EJ*, Firth AE* (2012) Efficient -2 frameshifting by mammalian ribosomes to synthesize an additional arterivirus protein. Proc Natl Acad Sci U S A 109:E2920-E2928.
  • Jagger BW, Wise HM, Kash JC, Walters KA, Wills NM, Xiao YL, Dunfee RL, Schwartzman LM, Ozinsky A, Bell GL, Dalton RM, Lo A, Efstathiou S, Atkins JF, Firth AE*, Taubenberger JK*, Digard P* (2012) An overlapping protein-coding region in influenza A virus segment 3 modulates the host response. Science 337:199-204.
  • Loughran G, Firth AE*, Atkins JF (2011) Ribosomal frameshifting into an overlapping gene in the 2B-encoding region of the cardiovirus genome. Proc Natl Acad Sci USA 108:E1111-E1119.
  • Chung BY, Miller WA, Atkins JF, Firth AE* (2008) An overlapping essential gene in the PotyviridaeProc Natl Acad Sci USA 105:5897-5902.