EASTBIO Regulating viral immunity via dendritic cell PTP1B: finding the right balance.

Supervisors:

Professor Mirela Delibegovic (University of Aberdeen)
https://www.abdn.ac.uk/ims/profiles/m.delibegovic

Professor John Forrester (University of Aberdeen)
https://www.abdn.ac.uk/ims/profiles/j.forrester

Professor Heather Wilson (University of Aberdeen)
www.abdn.ac.uk/ims/profiles/h.m.wilson

Dr Lucia Kuffova (University of Aberdeen)
https://www.abdn.ac.uk/ims/profiles/l.kuffova

This project has a single fundamental objective, namely to identify the mechanism of the PTP1B ON:OFF switch in the regulation of immunity.

Our extensive preliminary and recently published data suggest that, unexpectedly, the protein tyrosine phosphatase PTP1B, a central controller of cellular physiology, is active in dendritic cells (DC) and is required for optimal induction of T cell responses.
We aim to delineate precisely the role of PTP1B in viral pathogen clearance. Conversely, we will evaluate how effective inhibition of PTP1B is in down-regulating immune mediated pathology (herpes simplex keratitis, HSK).

We will address the following specific hypotheses: (1) Deletion and inhibition of PTP1B in DC exacerbates immune response to viral infection. (2) The immunosuppressive effects of PTP1B deletion in DC are predominantly due to DC defects in (a) trafficking or (b) induction of T cell activation.

Using the novel unpublished conditional Zbtb46 knockout (Zbtb-PTP1Bfl/fl) mouse model which is restricted to DC, we are uniquely placed to delineate the role of PTP1B in regulating DC function and immunity.

The long term objective is to clear the path towards the development of novel drugs which may modulate the immune system up or down, dependent on the condition / disease requiring treatment.

Application Procedure:

http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts to Alison McLeod at [Email Address Removed]. Two references should be provided by the deadline using the EASTBIO reference form. Please advise your referees to return the reference form to [Email Address Removed].