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Virus pathogenesis: interplay between the unfolded protein response and innate immunity.

Project Description

The unfolded protein response (UPR) is a cellular homeostatic response in restoring endoplasmic reticulum balance upon stress conditions e.g. virus infections. It is an evolutionary conserved tripartite response. However, the evolution of the UPR has continuously been shaped by the arms race between virus and the host. For some viruses the UPR has even become an integral part of their life cycles.

Recent evidence suggests that the UPR plays a role in innate immunity and virus sensing. Many virus infections stimulate a skewed UPR involving only a subset of the UPR molecules. Whereas a canonical tripartite UPR serves to restore homeostasis upon physiological endoplasmic reticulum (ER) stress, a skewed UPR can be sensed by the host as pathogenic invasion. Thus, a skewed UPR can be in itself a signal for launching the anti-viral and inflammatory responses.

Innate immunity is initiated by the sensing of pathogen associated molecular patterns by pattern recognition receptors. They converge onto the production of the anti-viral, interferon, and the inflammatory mediator, NF-B. Similar to the UPR, innate immunity has continuously been shaped by the arms race between virus and the host.

Enveloped RNA viruses manufacture a large amount of ER-resident proteins and ER transmembrane proteins and replicate via extensive re-modelling of the ER membrane, thus they interact intimately with the host UPR and are good models in the study of virus-host UPR interaction. Using RNA viruses such as hepatitis C virus and Zika virus as models, you will study how viruses interact with and manipulate the UPR to aid in their replication and its role in pathogenesis. You will study the roles of UPR molecules in virus sensing. You will study the synergistic activation of the UPR and innate immunity.

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with an interest in virology are encouraged to apply. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website ( Informal enquiries may be made directly to the primary supervisor.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.


Shiu-Wan Chan* (2014). ‘Unfolded protein response in virus infections’. Frontiers in Microbiology, Editorial.

Shiu-Wan Chan* (2014). Unfolded protein response in hepatitis C virus pathogenesis and chronicity. Frontiers in Microbiology, invited review.

Egan PA, Sobkowiak M, SW CHAN* (2013). Hepatitis C virus envelope protein E1 binds PERK and represses the unfolded protein response. The Open Virology Journal, 7:37-40.

*CHAN S. W. & Egan PA (2009). Effects of hepatitis C virus envelope glycoprotein unfolded protein response activation on translation and transcription. Archives of Virology, 154:1631-1640.

*CHAN S.W. & Egan PA (2005). Hepatitis C virus envelope proteins regulate CHOP via induction of the unfolded protein response. FASEB J., 19(11):1510-1512.

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