Investigation of Novel Accessory Proteins in the Replication of Infectious Bronchitis Virus

Description

Coronaviruses encode several accessory proteins that have been proposed to counteract antiviral host responses in vivo. Infectious Bronchitis Virus (IBV) is a Gammacoronavirus causing Infectious Bronchitis, an acute highly contagious economically important disease of chickens. IBV is related to other important coronaviruses such as SARS-CoV-2 or Middle East Respiratory Syndrome (MERS) coronavirus that infect humans. While previous research has shown that IBV genes 3 and 5 encode four accessory proteins, namely 3a, 3b, 5a and 5b; work in the Coronavirus group has identified two additional accessory genes, 4b and 7, produced via novel non-canonical mechanisms. This results in the production of three yet uncharacterised viral proteins denoted 4b and 4c and 7. The impact of these proteins during IBV replication is currently not known, however, our preliminary data suggests they have a role during in vivo infection with deletion impacting pathogenicity and that 4b could regulate translation, stress and/or mitochondrial function.

In a collaboration between the Coronavirus, Coronavirus Cellular Biology and Viral Stress Responses groups at The Pirbright Institute and groups at the University of Liverpool, this PhD project aims to investigate the role of these novel accessory proteins in IBV replication, and impact on antiviral host defences and pathogenicity. The project will use Mass spectrometry to identify host interaction partners hijacked or subverted by these proteins. Further assays targeting interferon induction and signalling, mitochondrial function, stress signalling, translation and autophagy will interrogate the potential roles of the proteins/interactions. Using reverse genetics and virology techniques such as growth kinetics, the role of the proteins in the replication of IBV in vitro, in ovo, ex vivo as well as in the replication and pathogenicity of IBV in vivo will be investigated.

The project represents a collaboration between three research groups at The Pirbright Institute as well as groups at The University of Liverpool, presenting an excellent opportunity to gain experience in a wide range of scientific techniques, scientific approaches and viewpoints. Throughout the PhD the prospective student will be encouraged to take advantage of these opportunities whilst being empowered to work independently and to achieve the confidence to generate ideas for the next steps. Attendance and presentation of work at seminars, journal clubs and conferences will be supported.

The student will be based primarily at The Pirbright Institute and registered with the University of Liverpool. It is expected that the student will spend some time at University of Liverpool to learn specific techniques such as Mass spectrometry. The student will visit the university to meet with their supervisors and undertake training or complete specific project tasks as required. Highly subsidised Pirbright Institute student housing will be offered. A full range of research and transferrable skills training will be made available to the student as appropriate.

This studentship is open to science graduates with, or who anticipate obtaining, at least a 2:1 or equivalent in a relevant biological subject in an undergraduate degree, or with a Masters degree - subject to university regulations. Other first degrees, e.g. veterinary science, will be considered. You should be looking for a challenging, interdisciplinary research training environment and have an active interest in the control of infectious diseases.

Students without English as a first language must provide evidence that they meet the English language requirement, e.g. with an average IELTS score of 7.0, with no lower than 7.0 in listening/reading and no lower than 6.5 in speaking/writing.

Applications for this PhD studentship must be made in the first instance to The Pirbright Institute.  For full details of how to apply please visit The Pirbright Institute website:  How to apply | The Pirbright Institute.  For any queries on the application process please contact: studentship@pirbright.ac.uk