PhD Opportunity – T cell/APC interactions and immunological decisions

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Project outline: It is becoming clear that the duration, frequency, and intensity of T cell/APC interactions, determines the induction of immunological tolerance versus priming. However, the detailed molecular mechanisms regulating cellular interactions in vivo remain unclear. We contend that spatiotemporal context has a critical influence on T/APC interactions and consequently the induction, maintenance and/or control of immune responses. For example, we have recently shown that the duration and magnitude antigen presentation and the subsequent T cell/APC interaction can influence differentiation of T cells to the Tfh phenotype responsible for driving B cell antibody production. Consequently, cellular and molecular interactions must be carefully choreographed in space and time to provide normal immune function giving protection against infection while avoiding autoimmunity. On the other hand, dysregulated spatiotemporal expression of molecules involved in T cell/APC interactions may result in pathology.

Summary aim: 

1. What are the molecular mechanisms controlling T/APC interactions during priming and tolerance in vivo?
2. How do these pathways impact on the duration, frequency and intensity of T cell/APC interactions in Lymph Nodes (LN)

Techniques to be used: High content (INCELL) imaging, Live in vitro microscope, Intravital multiphoton microscopy

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