Click here to apply Project Ref: 2016 06 ET/PK Oxford Anticipated Start Date: October 2016 Closing Date: 18 March 2016 Duration: 4 years full-time Project Title: Novel Mucosal T Lymphocytes In pigs. Eligibility: 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 is a fully-funded studentship only open to UK students and eligible EU students who qualify for homerated fees, in line with BBSRC criteria: http://www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/ Students without English as a first language must also provide evidence that they meet the English language requirement, e.g. with an IELTS score of 7.0 and no less than 6.5 in any of the subsections. Supervision: Principal Supervisors: Co-Supervisors: ` Elma Tchilian, The Pirbright Institute; Paul Klenerman, University of Oxford Hanneke Hemmink, The Pirbright Institute; Chris Willberg, University of Oxford Abstract: Mucosal associated invariant T cells (MAITs) and resident memory T cells (T RM), 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. T RM 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 T RM 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 T RM. 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. References for Background Reading: 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). Registration, Training and Funding: This is a BBSRC/University of Oxford fully funded project. The student will be based at The Pirbright Institute and registered with the University of Oxford, with visits to the university to meet with their supervisor and undertake training as required. Eligible students will receive a minimum annual stipend of £14,057 and university registration fees will be paid. A full range of research and transferrable skills training will be made available to the student as appropriate. Further information regarding the partner institutions can be found at: The Pirbright Institute University of Oxford Click here to apply Your application will only be considered if we have received the following documents: Application Form CV Two references sent directly by your referees