G3BP: A target for viral control of host cell biology

Viruses have been used as tools to probe cell biology since the early days of the discipline.

We have been studying the role of G3BP, a ubiquitously expressed RNA binding protein, involved in cellular stress responses in replication of alphaviruses and other viruses.

The protein is a common target for many viruses which seek to limit the responses to infection and to expedite their replication.

In this project we focus our investigations on the functions of G3BP in SARS-CoV-2 replication and on the development and use of novel assays which will elucidate more mechanisms of G3BP function in stress responses and under normal conditions. We will characterise the importance of G3BP in SARS-CoV-2 infection using two approaches.

In one, we have generated a panel of cell lines expressing different forms of the protein, and in the other, we have created a mutated form of the virus, which lacks a motif important for the recruitment of G3BP to viral replication complexes.

These orthogonal approaches will give unparalleled insight into the mechanisms by which G3BP is involved in viral replication.

In a second project, we aim for better structural and biochemical characterisation of other G3BP ligands such as UBAP2L, a positive regulator of stress granules and TRIM25, an E3 ubiquitin ligase involved in antiviral responses.

Finally, in a third project, we have established an in vitro assay for stress granule formation that will allow us to screen for SG-inhibiting nanobodies.