Interactions of Mycobacteria with innate immune cells and influence on adaptive responses
Bovine tuberculosis, caused by infection with Mycobacterium bovis, remains a significant threat to the UK farming industry and has zoonotic potential. BCG vaccination is protective (but not optimal) and interferes with diagnosis. The development of new vaccines and associated diagnostic tests is reliant on a better an understanding of how protective immune responses are initiated and controlled. We have previously shown that vaccination of calves with M. bovis BCG induces an influx of gamma delta (gd) T cells into lymph nodes and that these cells co-localise with antigen-presenting cells (APC). We hypothesise that APC are licenced through interactions with gd T cells to differentially prime adaptive alpha beta (αβ) T cell responses, and that by defining this process we will facilitate targeted vaccination strategies.
This project aims to improve current knowledge by:
Defining the interactions between gd T cells and M. bovis- or BCG-infected APC using purified cell subsets to investigate cell activation and proliferation.
Assessing polarisation of T cell responses. Naïve αβ T cells will be added to co-cultures of APC and gd T cells (total population or subsets as defined in (1)) and at a range of time points proliferation, activation and the expression of cytokines and signature transcription factors associated with Th subset differentiation will be assessed.
Defining mechanisms of the reciprocal interaction between APC and gd T cells that differentially drive T cell subset development. This will determine whether the interactions require cognate interactions or are cytokine (non-contact) driven. Specific candidate molecules identified in objective 1 will be blocked with specific mAb or siRNA will be used for knockdown as required.
The project will enable the PhD candidate to gain experience of a range of techniques in cellular immunology, host-pathogen interactions, molecular biology and cell biology.
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be sent to: Liz Archibald, The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG or emailed to [Email Address Removed].
When applying for the studentship please state clearly the title of the studentship and the supervisor/s in your covering letter.
All applicants should also apply through the University’s on-line application system for September 2016 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=831
International students should also apply for an Edinburgh Global Research Studentship (http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/international/global/research).
ALL APPLICATION PROCEDURES MUST BE COMPLETED BY THE CLOSING DATE 1st FEBRUARY 2016