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Department of Pathology

 

FULLY FUNDED PhD STUDENTSHIP IS AVAILABLE

APPLICATION DEADLINE 3rd December 2025!

https://www.path.cam.ac.uk/graduate/fully-funded-studentships

Our research focuses on the replication and pathogenicity of intestinal RNA viruses. Many common enteric viruses can also infect cells of the central nervous system, causing encephalitis, meningitis, and other complications. Picornaviruses and astroviruses stand out for their ability to infect cells of both gut and neuronal origins. We are using human intestinal and brain organoids as a platform to address organ-specific determinants of enteric virus infection and neuron infection model to dissect CNS-specific infections. We are developing a range of molecular tools to answer burning questions in enteric virus biology:

  • Elucidate host-pathogen interactions to uncover the molecular processes underlying different stages of infection, supported by defining the cell-type specificity of virus infection in both intestinal and neuronal cells.
  • Identify tissue-specific regulation of viral protein synthesis and specialised CNS host responses.
  • Uncover the roles of viral RNA structures in virus replication and neurovirulence.

Investigating these mechanisms in two diverse virus families will reveal common and virus-specific principles in host-pathogen interactions along the gut-to-brain axis. These findings will enhance our understanding of tissue-specific properties of clinically important pathogens, advancing the development of therapeutics and vaccines, and informing public health measures.

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://www.embo.org/funding/fellowships-grants-and-career-support/postdoctoral-fellowships/

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

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

Funding for our research comes from the Royal Society and Wellcome Trust: Sir Henry Dale Fellowship + Wellcome Career Development Award until 2034.

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:

David Noyvert (PhD student)

Dr Jacqueline Hankinson (Postdoctoral research associate)

Ksenia Fominykh (Research assistant)

Adam Rayment (PhD student, joint with Pirbright Institute)

Past lab members:

Dr Rhian O'Connor (PhD student, now postdoc at ICL), Dr Hashim Ali (2021-2023, PDRA, now at UCL), Gemma Lindsey (part II student), Samantha Cheng (EPLS Summer student), Morgan Reid (EPLS Summer student), and Imran Darr (part II student).

Publications

Key publications: 
  1. Lulla V and Sridhar A. Understanding neurotropic enteric viruses: routes of infection and mechanisms of attenuation. (2024) Review. Cell Mol Life Sci, 81(1):413.

  2. Ali H, Noyvert D, Hankinson J, Lindsey G, Lulla A., Lulla V. The astrovirus N-terminal nonstructural protein anchors replication complexes to the perinuclear ER membranes. (2024). PLOS Pathogens, 20(7):e1011959.

  3. 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.

  4. 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.

  5. Lulla V, Firth AE (2020). A hidden gene in astroviruses encodes a viroporin. Nature Communications, 11(1):4070.

  6. 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.

Complete publication list on Google Scholar

Group leader, Sir Henry Dale Fellow
Division of Virology

Contact Details

Takes PhD students
Available for consultancy

Affiliations