Investigating flavivirus biogenesis and immune evasion mechanisms
University of Oxford — Sir William Dunn School of Pathology
Dr S Sanyal
Tuesday, December 01, 2026
Competition Funded PhD Project (Students Worldwide)
About the Project
This project focuses on how (+)RNA viruses, particularly Dengue and Zika viruses assemble, spread, and evade host immune responses. Current understanding on how small (+)RNA viruses assemble and spread from cell to cell while evading innate and cellular immune responses is limited. This research aims to uncover the complex interplay between virus-induced cellular changes and host defence mechanisms. We are particularly interested in how these viruses trigger selective autophagy of lipid…
droplets, reorganise host secretory pathways, while downregulating immune receptors, MHC-I/II antigen presentation and interferon production.
We have identified host factors (e.g. ubiquitylation enzymes, GTPases) that are targeted by these pathogens to impair ER-phagy while inducing lipophagy and unconventional secretory processes1-4. We will apply CRISPR/Cas9 gene editing technology combined with biochemical and cell biological methods and functional assays to investigate how specific genes affect virus assembly and secretion, while subverting innate and cellular immune responses to drive pathogenesis5-7.
The project will employ a range of cutting-edge methodologies, including CRISPR/Cas9 gene editing, biochemical and cell biological techniques, functional assays, and quantitative mass spectrometry. These will be complemented by approaches from immunology and virology. Through this multidisciplinary approach, we aim to elucidate the intricate relationships between host cellular pathways and viral biogenesis, as well as the mechanisms of immune evasion that drive pathogenesis.
Funding Notes
4 Year DPhil Prize Studentships cover full University fees, a tax free enhanced stipend of ~£24,305 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See the institution website for full details and to apply.
References
- Li MY, Deng K, Cheng X, Siu L, Gao Z, Naik TS, Stancheva VG, Cheung P, Teo QW, van Leur SW, Wong HH, Lan Y, Lam TT, Sun MX, Zhang NN, Zhang Y, Cao TS, Yang F, Deng YQ, Sanyal S*, Qin CF*. Targeting ARF4-mediated intracellular transport as a broad-spectrum antiviral strategy (2025) Nat Microbiology 10(3):710-723
- Trejo-Cerro O, Beekmayer-Dhillon A, Teo QW, Siu L, Li MY and Sanyal S*. UCHL3 regulates subgenomic flaviviral RNA condensates to promote virus propagation (2026) Advanced Science e21781
- Lan Y, van Leur SW et al and Sanyal S. Viral subversion of ER-phagy is critical to membrane remodelling for biogenesis of (+)RNA virus replication organelles (2023) Nature Communications 14(1): 2698
- Li MY, Naik TS, Siu LYL, Acuto O, Spooner E, Wang P, Yang X, Lin Y, Ashour J, Evans MJ and Sanyal S. Lyn kinase regulates egress of flaviviruses in autophagosome-derived organelles (2020) Nature Communications 11: 5189
- Zhang J, Lan Y, Li MY, Lamers MM, Fusade-Boyer M, Klemm E, Thiele C, Ashour J and Sanyal S. Flaviviruses exploit the lipid droplet protein AUP1 to trigger lipophagy and drive virus production (2018) Cell Host Microbe. 23 (6): 819-831
- Munnur D et al and Sanyal S Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection (2021) Nature Immunology 22(11): 1416-1427
- Teo QW et al and Sanyal S. Usp25-Erlin1/2 limits cholesterol flux to restrict a broad range of viruses. (2023) Developmental Cell 58 (22): 2495-2509
