Phosphoproteomics in early T-cell signalling

Summary

Using proteomics to understand T-cell signalling/signal transduction.

Supervisor(s)

Professor Nicholas Manolios

Research Location

Westmead - Westmead Clinical School

Program Type

PHD

Synopsis

This project focuses on the structure-function correlations underlying T-cell antigen receptor (TCR) responses directed towards antigen. The exact molecular arrangement of this TCR/CD3 complex and the spatial positioning of the contact sites leading to signalling have not been fully elucidated. Recent functional insights gained from our studies on TCR signalling has enabled us to extend the current system of belief and propose a novel model of T-cell activation to be tested in this proposal. We will use proteomic techniques to identify phosphotyrosines that are involved in early stage T-cell signalling; and modern in silico computational analysis to design and test peptides able to inhibit TCR-b/CD3-eg interactions. More specifically:

  1. Apply phosphoproteomic techniques to define the role of specific phosphotyrosine proteins in TCR signal transduction and thereby help to dissect the functional signalling modules involved with T-cell activation following ANTIGEN stimulation.
  2. Use both target and ligand-based in silico computational techniques to investigate and establish the nature of contributing extra-cellular binding interactions specific to TCR-b and CD3-e.

Additional Information

Funding available.

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Keywords

Proteomics, T-cells, Signal transduction, phosphotyrosines, Infectious diseases, Cell biology, Infection & immunity

Opportunity ID

The opportunity ID for this research opportunity is: 21

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