PhD Studentship: Understanding Mechanisms Involved in Immunosuppression Induced by Porcine Reproductive and Respiratory Syndrome Viruses

The project:

Research Theme: Infection, Inflammation and Immunotherapy

The porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant threat to the global pig industry, causing reproductive failure, respiratory issues, and immunosuppression. Research suggests that the PRRSV NSP2 protein activates the COX2/PGE2 pathway and is linked to regulatory T (Treg) cell responses, contributing to immunosuppression. In our prior work, we found that the COX2/PGE2 pathway, activated by NSP2, upregulates Treg expansion in a TGF-β dependent manner.

This project aims to investigate the role of the COX2/PGE2 pathway in modulating immune responses in pigs following viral infections. The hypothesis is that PRRSV NSP2 activates the pathway in infected macrophages, leading to TGF-β maturation and Treg cell activation, negatively regulating the immune response. Using RT-qPCR, western blot, ELISA, flow cytometry, and a luciferase-based bioassay, the project seeks to assess pathway activation, explore TGF-β-induced Treg cell responses in vitro, and determine the impact of PRRSV mutations on immune responses in vivo.

The student will gain experiences working across three laboratories (Pirbright, Bristol and BIOTEC (Thailand); and will learn and apply a range of state-of-the-art immunological and molecular virology techniques.

References:

Montaner-Tarbes S, et al. Front Vet Sci. 2019. 6:38.

Du L, et al. Front Immunol. 2021. 12:657071.

Lead Supervisor: Professor Shahriar Behboudi, Bristol Veterinary School, Faculty of Health Sciences

Co-Supervisors: Dr Benedetta Amato, Professor Mick Bailey (University of Bristol)

Institute supervisors: Dr. Rory Fortes de Brito, Professor Simon Graham (The Pirbright Institute);

Collaborator: Nanachaya Wanasen (BIOTEC, Thailand)

Start date: 9^th September 2024

How to apply:

Please make an online application for this project at http://www.bris.ac.uk/pg-howtoapply. Please select on the Programme Choice page. You will be prompted to enter details of the studentship in the Funding and Research Details sections of the form. In the funding section of the application form, select ‘Studentship’ as the main source of funding and enter ‘Understanding mechanisms involved in immunosuppression induced by porcine reproductive and respiratory syndrome viruses’.

Candidate requirements:  Standard University of Bristol eligibility rules apply.

Please visit PhD Veterinary Sciences | Study at Bristol | University of Bristol for more information.

Funding:

Fully funded studentship from University of Bristol and The Pirbright institute 'subject to contract’. Allowance per year: £19,237 (with annual increments), stipend top-up (a high cost of living allowance of £2.2k/yr) provided by the Pirbright Institute, tuition fee: £4,758 (with annual increments) for UK students.

Overseas students are welcome to apply but must be able to fund the difference between UK and Overseas tuition fees.

Contacts: Professor Shahriar Behboudi s.behboudi@bristol.ac.uk

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