Phosphoproteomics in early T-cell signalling

Summary

Using phospho-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 relationships underlying T-cell antigen receptor (TCR) activation following antigen recognition. The exact molecular arrangement of the TCR/CD3 complex and the spatial positioning of these contact sites leading to signalling have not been fully elucidated. Recent functional insights gained from our studies on TCR signalling have enabled us to extend the current signaling paradigm and propose a novel and alternate pathway involved with TCR signalling. We will use proteomic techniques to identify which proteins are involved in early stage T-cell signalling and prove or disprove the alternate pathway hypothesis. The second phase of the project using in silico computational analysis would be to design and test peptides able to inhibit either of the pathways identified. More specifically: 
1. Apply phospho-proteomic techniques to define proteins in TCR signal transduction 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 and other peptide inhibitors of TCR signalling pathways.

Additional Information

Funding available.

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Keywords

Proteomics, T-cells, Signal transduction, phospho-tyrosines

Opportunity ID

The opportunity ID for this research opportunity is: 21

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