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Unravelling the mechanism of viral factory formation. An unexplored target for the development of novel antivirals (fully funded PhD).


Faculty of Biological Sciences

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Dr Anton Calabrese No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

Viral replication factories (sites of viral replication/assembly) are formed when a number of important human and animal pathogens infect cells, including influenza, rabies, measles and rotavirus. Since viral factory formation is a virus-specific process, they represent excellent antiviral targets. However, the molecular mechanism of viral factory assembly, and their precise role in virus replication remain unexplained, hampering the development of therapeutic strategies targeting this process.

In this project, you will study the structure, dynamics and interactions of the non-structural proteins that mediate viral factory assembly in Rotavirus (the major cause of >200,000 child deaths per annum). You will use a suite of structural proteomics tools, including native ion mobility-mass spectrometry, chemical crosslinking and hydrogen-deuterium exchange. The ultimate aim of this work is to determine if targeting proteins that form viral factories is a viable, novel therapeutic strategy to combat viral infections.

You will work under the supervision of Dr Anton Calabrese (http://www.calabreselab.com/) 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 approaches to characterise protein-protein and protein-small molecule interactions.

Please apply online (https://studentservices.leeds.ac.uk/pls/banprod/bwskalog_uol.P_DispLoginNon). Include a CV and transcripts, and state Dr Calabrese as your nominated supervisor


Funding Notes

Fully funded studentship, providing UK/EU fees plus research council level stipend for 3.5 years.

Please apply online (https://studentservices.leeds.ac.uk/pls/banprod/bwskalog_uol.P_DispLoginNon). Include a CV and transcripts, and state Dr Calabrese as your nominated supervisor

References

J. E. Horne, M. Walko, A. N. Calabrese, M. A. Levenstein, D. J. Brockwell, N. Kapur, A. J. Wilson, S. E. Radford, Rapid mapping of protein interactions using tag-transfer photocrosslinkers, Angew. Chem. Int. Ed., 2018, 57, 16688-16692

J. P. K. Bravo, A. Borodavka, A. Barth, A. N. Calabrese, P. Mojzes, J. J. B. Cockburn, D. C. Lamb, R. Tuma, Stability of local secondary structure determines selectivity of viral RNA chaperones, Nucleic Acids Res., 2018, 46, 7924-7937

A. N. Calabrese, S. E. Radford, Mass spectrometry-enabled structural biology of membrane proteins, Methods, 2018, 147, 187-205
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