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Department of Pathology

 

Our group focuses on the replication and pathogenicity of intestinal RNA viruses using enteroviruses and astroviruses as model systems. Both virus groups include zoonotic pathogens, and both include members that can escape the gut to infect the central nervous system. We are developing a range of molecular tools to address fundamental issues in enterovirus and astrovirus biology:
 - Regulation of translation, replication and virus release
 - Features of virus replication in the gut-specific environment
 - Conserved RNA elements, their functions and therapeutic potential
 - Determinants of neurovirulence

Summer students - apply here: https://www.exppg.lifesci.cam.ac.uk/

MPhil students - apply here: https://www.mphil.bio.cam.ac.uk/

Postdocs - happy to support fellowship-based projects:

https://marie-sklodowska-curie-actions.ec.europa.eu/actions/postdoctoral-fellowships

https://royalsociety.org/grants-schemes-awards/grants/newton-international/

Funding for research comes from the Royal Society, Wellcome Trust, and MRC.

Research

Project: Replication and pathogenicity of intestinal RNA viruses

Characterisation of the novel uORF in enteroviruses
We have recently reported that enteroviruses encode an additional protein in an upstream open reading frame (uORF). Knocking out expression of the uORF protein (termed “UP”, Upstream Protein) attenuates virus growth at late stages of infection in human intestinal organoids but not in standard cell culture systems, suggesting a specific role for UP during establishment of infection in gut epithelia in the initial stages of virus invasion into susceptible hosts (Lulla et al., Nature Microbiology, 2019). Current work focuses on understanding how UP expression is controlled, the role(s) of UP in different enterovirus species, characterisation of UP-mediated virus release in gut epithelial cells as well as potential related vaccine strategies.

Characterisation of astrovirus replication and pathogenicity
Astroviruses are one of the most prevalent groups of human RNA viruses. However, they are critically understudied because of the lack of good molecular tools and animal models. Despite the appearance of recently emerged strains and increasing detection of astroviruses as previously overlooked causative agents of gastroenteritis, the current lack of molecular understanding and expertise precludes the efficient development of therapeutic approaches. We have recently identified and characterised a new ORF encoded by astroviruses (Lulla and Firth, Nature Communications, 2020) and already used the developed astrovirus replicon system to aid a SARS-CoV-2 related project (Lulla et al., Journal of Virology, 2021). This project will focus on understanding the formation of the astrovirus replication complex, RNA synthesis mechanisms, proteolytic processing, gut-specific determinants, and the molecular mechanisms responsible for neurovirulence.

Funding for our research comes from the MRC, the Royal Society and the Wellcome Trust.
 

Group members:

Rhian O’Connor (final year MRC DTP PhD student)

David Noyvert (2nd year PhD student)

Jacqueline Hankinson (Postdoctoral research associate)

Past lab members:

Hashim Ali (2021-2023, PDRA, now at UCL)

Publications

Key publications: 
  1. Ali H, Noyvert D, Hankinson J, Lindsey G, Lulla V*. The astrovirus N-terminal nonstructural protein anchors replication complexes to the perinuclear ER membranes. (2024). BioRxiv.
  2. Ali H, Lulla A, Nicholson AS, Hankinson J, Wignall-Fleming EB, O'Connor RL, Vu D-L, Graham SC, Deane JE, Guix S, Lulla V*. Attenuation hotspots in neurotropic human astroviruses. (2023). PLOS Biology, 21(7):e3001815.
  3. Lulla V*, Wandel M, Bandyra KJ, Ulferts R, Wu M, Dendooven T, Yang X, Doyle N, Oerum S, Beale R, O’Rourke S, Randow F, Maier H, Scott W*, Ding Y*, Firth AE*, Bloznelyte K*, Luisi B*. (2021). Targeting the conserved stem loop 2 motif in the SARS-CoV-2 genome. Journal of Virology, 95(14):e0066321.
  4. Lulla V*, Firth AE* (2020). A hidden gene in astroviruses encodes a viroporin. Nature Communications, 11(1):4070.
  5. 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. Nature Microbiology, 4(2):280-292.

* Corresponding authors

Complete publication list on Google Scholar

Group leader, Sir Henry Dale Fellow
Division of Virology

Contact Details

Takes PhD students
Available for consultancy

Affiliations