Supervisors: Valeria Lulla and Dr David Noyvert

Many common enteric viruses can also infect cells of the central nervous system (CNS). Such neurotropic viruses infect >50 million people annually, causing encephalitis, meningitis, and other complications. Picornaviruses and astroviruses stand out for their ability to infect cells of both gut and neuronal origins. This project seeks to understand the molecular basis of how enteric viruses can display both neurovirulence and gut-specific replication.

A long-standing question regarding the biology of these viruses is: How do viruses replicate in tissues of both gut and brain origin? Identifying the molecular signatures underlying gut- and brain-specific replication is vital for therapeutic development. We recently made fundamental discoveries in this field: the first neurotropic determinants in astroviruses (Ali et al., 2023) and modulation of translation initiation in enteroviruses that is specific to terminally differentiated cells (O’Connor et al., 2026). These are examples of molecular regulation in a cell-type-specific manner that set the ground for further research using techniques developed in our group.

In this PhD project, you will investigate molecular mechanisms of host-pathogen interactions in neuronal and intestinal cells. You will use cutting-edge technologies, combining molecular virology, genome editing, virus evolution, and organoid infection models, to address fundamental questions about host-pathogen interactions in tissue/cell-specific environments.

This project will provide outstanding interdisciplinary training in infection biology, organoid infection models, host-pathogen interactions, as well as highly transferable quantitative and molecular skills.

Publications

1. Noyvert D, Neves LX, Fominykh K, Hankinson J, Lindsey G, Lulla A, Emmott E, Lulla V. Viral protease-mediated polyprotein processing in human astroviruses. (2026). NPJ Viruses, PMID: 42286165
2. Noyvert D, Darr IM, Fominykh K, Hankinson J, Lukhovitskaya N, Firth AE, Lulla V. The dynamics and strategy of RNA replication in astroviruses.(2026). NAR Mol Med, 3(2):ugag021. PMID: 42087922
3. O’Connor RL, Cook GM, Hankinson J, Fominykh K, Cheng SH, Nash D, Cenier A, Nayak KM, Graham SG, Deane JE, Zilbauer M, Firth AE, Lulla V. Flexibility and modulation of translation initiation in enterovirus genomes. (2026). PLOS Pathogens, 22(2): e1013967. PMID: 41662385
4. 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. PMID: 39365457
5. 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. PMID: 39008516
6. 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. (2023). Attenuation hotspots in neurotropic human astroviruses. PLOS Biology, 21(7):e3001815. PMID: 37459343