Investigating the folding of influenza and coronavirus fusion proteins within the endoplasmic reticulum

This is a summer student position supervised by Luke Perera in Steve Gamblin's lab.

Introduction to the science

The lab focuses on understanding the mechanism and structure of disease related proteins. We have a particular interest in viral fusion proteins and in heterochromatin regulation. We employ a wide range of cell-based, biophysical, biochemical and structural biology techniques to investigate these processes.

About the project

Influenza and coronavirus fusion proteins (hemagglutinin and spike, respectively) contain a number of disulphide bonds in their mature, fully folded states. These viral fusion proteins (VFPs) are co-translationally secreted into the endoplasmic reticulum (ER) where, in the presence of ER chaperones, they undergo oxidative protein folding. The details of this folding pathway and the protein folding chaperones that are required for these processes are incompletely understood.

By developing inducible cell lines and utilising click chemistry-based pulse-chase techniques, the student will be involved in establishing a methodology for following and halting the folding pathway of VFPs and trapping endogenous folding intermediates/complexes. Ultimately, we hope to biochemically and structurally characterise VFP folding intermediates. These efforts will both inform our knowledge of a process essential for viral replication and of the much more ubiquitous process of oxidative folding within the ER.

Candidate background