Face off – dissecting the role of phase separation in viral replication and antiviral responses

Background:

The assembly of membraneless organelles is emerging as a fundamental paradigm for many cellular functions. Among these, stress granules (SGs) play a central role in health and disease by concentrating proteins and RNAs, driving adaption to stressful conditions, including viral infection. SGs can be either cytoprotective or pro-death, anti-viral or pro-viral. SGs are proposed to act as part of larger coordinated waves of biocondensates assembly in the nucleus – paraspeckles which impact on splicing, and interact with cytoplasmic P-bodies involved in RNA decay. Despite this, the role of biocondensates in infection remains poorly understood. Because SGs and paraspeckles can have anti-viral functions, or promote replication, viruses provide a unique model to elucidate biocondensate functions. At Surrey, Professor Locker has already made fundamental advances in understanding SG function. With its nuclear replication and Professor West’s work at Sussex showing it repurposes cellular RNA binding proteins to regulate gene expression, Epstein-Barr Virus (EBV) provides an excellent to dissect the role of biocondensates during viral infection.  

Objectives:

To understand how biocondensates contribute to EBV infection you will:  

1. Characterise the distinguishing features of biocondensates present in EBV-infected cells, their structures, kinetics and interactions (fixed, live and high-resolution imaging)
2. Establish how do biocondensates contribute to and manipulate host responses to EBV infection and viral replication (biochemical approaches, cell-based assays) 
3. Develop novel approaches to study the composition of biocondensates in the physiologically relevant context of EBV-infected tumour cells (particles sorting, omics approaches). 

Determining how biocondensates direct specialised functions will establish new rules governing host responses to infection. This improved understanding of the role of phase separation during viral infection could inform novel therapeutic approaches. 

A good honours degree (upper second) in an appropriate discipline. See our PhD programme page for details.

English Language requirements 

IELTS score of 6.5 overall, with no lower than 6.0 in writing, or equivalent.

Supervisory team

This is a collaborative project between the Universities of Surrey and Sussex. Nicolas Locker is a Professor of Virology at Surrey with interests at the interface between RNA biology and virology. His work focuses on understanding how viruses manipulates cellular stress responses during infection to favour replication. At Sussex, Michelle West is a Professor of Tumour Virology with over 20 yrs of experience in dissecting the molecular virology of Epstein Barr Virus, and exploring the interface between cancer biology and virology. She will provide expertise in the viral and cellular models required for this project, and access to outstanding imaging facilities at Sussex.  

References for information

Prof. Locker recent work: https://pubmed.ncbi.nlm.nih.gov/?term=Locker+N.&sort=date

General review on stress granules and viruses: https://pubmed.ncbi.nlm.nih.gov/32899736/