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Characterisation of porcine T follicular helper cells and their response to vaccination and infection


   Doctoral Training Centre

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  Dr Jane Edwards, Dr Wilhelm Gerner, Dr P Borrow  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Since they were first discovered in 2000, the function of T follicular helper (Tfh) cells has been a subject of intense and fast-moving research. It is now clear that these cells are critical in orchestrating the B cell/antibody response and they have become a focus in improving targeted cancer immunotherapy and vaccine strategies. In humans and mice, Tfh are characterised by expression of CXC chemokine receptor 5 (CXCR5), inducible T cell costimulatory (ICOS), programmed cell death protein 1 (PD-1), T-cell lymphoma 6 (Bcl-6) and interleukin 21 (IL-21). It is now clear that at least five phenotypes exist across secondary lymphoid tissues and in circulation, each prevalent at different stages of the immune response and each expressing different levels of the archetypal Tfh phenotypic markers. Notably, in both SARS-CoV-2 and HIV infection an increased frequency of circulating Tfh correlates with decreased disease severity and enhanced neutralising antibody responses, respectively. 

There are limited studies on Tfh cells in the pig, which is both a major food producing species and an important biomedical model. This project therefore intends to expand our knowledge of the phenotype and function of porcine Tfh cells. We have demonstrated cross-species reactivity of several Tfh markers, including Bcl-6 and ICOS, and in collaboration with the Roslin Institute, developed a reagent for labelling of CXCR5-expressing cells. The first aim of the project is to further develop and optimise staining panels for both flow cytometry and confocal microscopy applications to identify and characterise porcine Tfh in blood and secondary lymphoid organs. Defined Tfh-like populations will be cell sorted and assessed in functional assays involving assessment of antibody production from co-cultured syngeneic B cells. Sorted cells will be further characterised by RNAseq transcriptomic analysis. Funding permitting, a spatial transcriptomic analysis, whereby the spatial location of each cell is determined and accounted for, may be performed on lymphoid organ sections. Finally, the tools developed will be applied in the context of vaccination and infection. For example, assessing the frequency and phenotype of circulating and tissue resident Tfh during infection with the porcine reproductive and respiratory syndrome virus (PRRSV). Tfh response profiles will be compared to CXCL13, IL-21 and IL-6 levels in serum, virus loads in blood and tissues and neutralising antibody responses to determine whether associations exist.

This project will improve our fundamental understanding of Tfh in the pig and should provide insights into how they regulate humoral immunity. Harnessing the potential of Tfh cells in future vaccine design should lead to improved disease control, with significant economic and animal welfare benefits.

Attributes of suitable applicants:

  • A basic understanding of immunology, obtained as part of an undergraduate or MSc programme.
  • An interest in comparative/veterinary immunology and its application to improve animal health.
  • Able to problem solve and be creative in generating a solution whilst also able to perform the same activity in a consistent manner.
  • Excellent collaboration and communication skills. 
  • Able to work independently and as part of a team.

How to apply:

Applicants should first contact the lead supervisor to discuss whether their research interests are a suitable fit for the project, read this page carefully and then apply online via this page. Please note that we are implementing measures to limit implicit bias in the application process and taking positive action to support students from groups that are under-represented in bioscience. Applicants therefore need to follow the instructions on this webpage when preparing an application.

NB:

This project is supported through the Oxford Interdisciplinary Bioscience Doctoral Training Partnership (DTP) studentship programme. The student recruited to this project will join a cohort of students enrolled in the DTP’s interdisciplinary training programme, and will participate in the training and networking opportunities available through the DTP. For further details, please visit www.biodtp.ox.ac.uk. The DTP and its associated partner organisations aim to create a community that is innovative, inclusive and collaborative, in which everyone feels valued, respected, and supported, and we encourage applications from a diverse range of qualified applicants.


Funding Notes

This project is funded for four years by the Pirbright Institute and the Biotechnology and Biological Sciences Research Council UKRI-BBSRC. UKRI-BBSRC eligibility criteria apply (https://www.ukri.org/files/funding/ukri-training-grant-terms-and-conditions-guidance-pdf/). Successful students will receive a stipend of no less than the standard UKRI stipend rate, currently set at £16,062 per year.
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