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Insights into the assembly of viral factories from structural mass spectrometry


Project Description

Viral replication factories in cells (sites of viral replication/assembly) are formed by viral non-structural proteins (NSPs) in a number of important human and animal pathogens, including Reoviruses and Rotaviruses (the major cause of >200,000 child deaths per annum). However, the molecular mechanism of viral factory assembly, and their precise role in virus replication remain unexplained. In this project, mass spectrometry based methods will be developed to understand the structure, dynamics and interactions of the non-structural proteins that mediate viral factory assembly, using non-structural proteins from Rotavirus as a model system. A suite of mass spectrometry-based tools, including native ion mobility-mass spectrometry, chemical crosslinking, hydrogen-deuterium exchange and fast photochemical oxidation of proteins, will be used to interrogate the structure, conformational dynamics and interactions of the proteins that are essential for viral factory assembly.

The ultimate aim of this work is to determine if targeting viral factory formation is a viable, novel strategy to combat viral infections.

You will work under the supervision of Dr Anton Calabrese (http://www.calabreselab.com/) (co-supervised by Prof Frank Sobott) in Leeds’ world class Biomolecular Mass Spectrometry laboratory which houses 7 instruments dedicated to structural mass spectrometry. This is a collaborative project with Dr Alex Borodavka’s laboratory at the University of Cambridge (https://www.infectiousdisease.cam.ac.uk/directory/alex-borodavka). You will receive training in structural mass spectrometry methodologies, molecular biology techniques and other biophysical approaches to characterise protein-protein and protein-small molecule interactions, and push the limits of current structural mass spectrometry capabilities.

Funding Notes

Fully funded studentship, providing UK/EU fees plus research council level stipend for 3.5 years.
Please apply online View Website
include a CV and transcripts, and state Dr Calabrese as your nominated supervisor

How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

Research output data provided by the Research Excellence Framework (REF)

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