Dissecting the immunosuppressive effects of Marek’s disease virus

Oncogenic viruses have evolved various mechanisms to escape immune control and promote tumour development. One such mechanism is the activation of pathways leading to metabolic changes that can influence physiological and immunological activities in the infected individuals; in some viral infections this manifests itself as the production of Prostaglandins which manipulate immunological responses against both viruses and tumours.

Our group has shown that Marek’s disease virus, an avian oncogenic virus, induces the expansion of novel regulatory T cells in infected chickens, and this may explain the immunosuppression observed in these birds (Gurung et al. PLoS Pathogen 2017). We have also shown that Marek’s disease virus activates metabolic changes (Boodhoo et al. Journal of Virology 2019, Boodhoo et al. Journal of Virology January 2020, Boodhoo et al. Journal of Virology September 2020), including the production of Prostaglandins. Marek’s disease virus expresses over 80 different viral proteins in the infected cells. Based on this information, the PhD candidate will use in vitro systems to identify the gene(s) of Marek’s disease virus which activate regulatory T cells via induction of Prostaglandins.

The student will join a successful, motivated multidisciplinary team with expertise in cellular and molecular immunology, virology, and metabolism. A combination of cellular and molecular immunology as well as classical virology techniques including flow cytometry, confocal microscopy, metabolic analysis, molecular biology, and gene silencing will be utilised in this project.

Supervisors:

• Dr Shahriar Behboudi, The Pirbright Institute
• Dr Natalie Riddell, University of Surrey
• Co-supervisor - Dr Ajit Patil, The Pirbright Institute

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 their undergraduate degree, or 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.

This studentship is open to UK students and eligible EU students who qualify for home-rated fees, in line with Residential Guidelines for Research Council Studentships.

English Language requirements 

Students without English as a first language must provide evidence that they meet the English language requirement, e.g. 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.

Research group: Avian oncogenic viruses.

The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans. We receive strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC), and work to enhance capability to contain, control and eliminate these economically and medically important diseases through highly innovative fundamental and applied bioscience. The Institute employs around 350 staff, research students and visiting scientists, and is based in Pirbright, Surrey, where investment by BBSRC has resulted in a redevelopment of the site and the construction of a high level containment facility – the BBSRC National Virology Centre: The Plowright Building and a SAPO level two facility, The Jenner Building.  https://www.pirbright.ac.uk.

References for Background Reading:

1. Boodhoo N, Gurung A, Sharif S, Behboudi S. Marek’s disease in chickens; a review with focus on immunology. Veterinary Research, 2016 November 28: 47(1);119.
2. Gurung A, Kamble N, Kaufer B, Pathan A, Shahriar Behboudi. Association of Marek’s Disease induced immunosuppression with activation of a novel regulatory T cells in chickens, PLoS Pathogens, 2017, 13 (12), e1006745.
3. Boodhoo N, Kamble N, Kaufer BB, Behboudi S. Replication of Marek’s disease virus is dependent on de novo synthesis of fatty acid and Prostaglandin E2. J Virol. 2019 Jun 14;93(13).
4. Boodhoo N, Kamble N, Sharif S, Behboudi S. Glutaminolysis and Glycolysis are essential for optimal replication of Marek’s disease virus. J Virol. 2020 Jan 31;94(4).
5. Boodhoo N, Kamble N, Behboudi S. De Novo Cholesterol Biosynthesis and Its Trafficking in LAMP-1 Positive Vesicles Are Involved in Replication and Spread of Marek’s Disease Virus, J Virol. 2020 Sep. In press.