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Novel Mucosal T Lymphocytes in pigs

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  • Full or part time
    Dr Tchilian
    Prof Klenerman
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Mucosal associated invariant T cells (MAITs) and resident memory T cells (TRM), are recently identified populations of white blood cells which play pivotal roles in protection against pathogens. MAITS are a bridge between the earliest non-specific responses to infection (innate immunity) and the later specific (adaptive) responses of antibody forming cells and T cells. TRM stay in tissues and do not circulate through the blood like other T cells. However there is no information about the roles of these cells in protection against swine influenza (SI) infection of the respiratory tract of pigs. SI is one of the most important primary swine respiratory pathogens and is a zoonotic threat. SI viruses are implicated in human influenza, both as a source of occupational exposure and as a contributing source of new human influenza strains. In this project we shall determine the role of MAITs and TRM in SI infection with the following objectives.

1. Enumeration of MAITs and TRM. Development of an MR1 tetramer (in Paul Klenerman’s lab in Oxford) will facilitate MAIT identification and isolation.
2. Determination of the effects of immunisation or SI infection on MAITs and TRM. The number, phenotype and distribution of MAITs/TRM will be assessed by flow cytometry or immuno-histology. Multiparametric phenotypic analyses (>30 parameters per cell) will be performed in Oxford using the Zellscanner 1 machine.
3. Determination of the function of pig MAITs and TRM. Methods will include proliferation following CFSE labelling, intra-cytoplasmic staining for cytokines and cytotoxic killing assays following TCR and cytokine stimulation. We will test the response to SI infection in vitro using autologous SI infected macrophages, bacterial ligand, pdmH1N1 influenza virus, anti-CD3 and PMA/Ionomycin stimulation.
This project falls within the One Health initiative as an interdisciplinary collaboration between human and veterinary immunologists which will deliver information not only useful for development of a vaccine for SI in pigs but for humans.

Funding Notes

A BBSRC fully funded project open to UK students and eligible EU students who qualify for home-rated fees in line with BBSRC criteria:
http://www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/
Eligible students will receive a minimum tax-free stipend of £14,057 - university fees will be paid.
Open to science graduates (with, or who anticipate, at least a 2.1 or equivalent in a relevant biological subject in an undergraduate degree, or a Masters degree - subject to university regulations). Other first degrees considered.
Students without English as a first language must provide evidence of IELTS score of 7.0, no less than 6.5 in any subsections (or equivalent).

References

1. Kurioka, A. et al. MAIT cells are licensed through granzyme exchange to kill bacterially sensitized targets. Mucosal immunology 8, 429-440 (2015).
2. Steinert, E.M., et al. Quantifying Memory CD8 T Cells Reveals Regionalization of Immunosurveillance. Cell 161, 737-749 (2015).
3. Rajao, D. S. & Vincent, A. L. Swine as a model for influenza A virus infection and immunity. ILAR journal 56, 44-52(2015).

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