"Closing Date: 30th June 2010
Details:
Supervisors: Dr J Palmer and Dr A Knight
Institute/School: Institute of Cellular Medicine
Sponsor: Faculty of Medical Sciences and the Institute of Cellular Medicine
Duration of the award: 3 years
This PhD project will study mechanisms of autoantigen presentation in the autoimmune liver disease Primary Biliary Cirrhosis (PBC). The successful applicant will join the Applied Immunobiology group within the Institute of Cellular Medicine.
The autoimmune liver disease, Primary Biliary Cirrhosis (PBC), results from a breakdown in CD4+ T cell tolerance to the ubiquitously expressed mitochondrial pyruvate dehydrogenase complex (PDC). The major T & B cell immunogenic region has been mapped to the inner lipoyl domain of the E2 component of PDC. One of the key steps involved in disease initiation appears to be the relocation of this intracellular autoantigen to the surface of apoptotic intrahepatic biliary epithelial cells (HIBEC).
Using a mouse model of PBC, we have previously demonstrated an antigen presenting role for B cells in the activation of PDC-E2 specific CD4+ T cells. In separate studies we have also recently demonstrated that antigen-specific B cells are capable of physically extracting intracellular antigens that have relocated to the cell surface of apoptotic cells. Importantly, we have also shown this novel means of antigen acquisition by B cells leads to CD4+ T cell activation.
This project will test the hypothesis that B cells represent an important population of antigen presenting cells (APC) responsible for the initiation of anti-PDC responses by acquiring mitochondrial antigens relocated to the plasma membrane of HIBEC following the induction of apoptosis.
Project start date: October 2010
Eligibility and Value of the Award
The award covers UK/EU tuition fees and an annual tax free stipend of approximately £13,489 per year. International students may apply but will need to source additional funding to cover the difference between UK/EU and international tuition fees.
Person Specification
You should have, or expect to achieve, a first-class, or upper-second-class, Honours degree and a MRes in a relevant subject.
How to Apply
You must complete the University's postgraduate application form. Select "PhD in the Faculty of Medical Sciences – Cellular Medicine" as the programme of study. Only mandatory fields need to be completed (no personal statement required) but you must attach a copy of your CV and a covering letter, quoting the title of the studentship and reference number CL026.
Further Information
For more details, please contact Dr J Palmer, J.M.Palmer@ncl.ac.uk, or Dr A Knight, Andrew.Knight@ncl.ac.uk"
Fonte: Newcastle University
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