A Proteomics Approach to Understanding the Role of the Tec Protein
The Tec tyrosine kinase has been implicated in signalling from numerous cellular receptors including T-cell receptor, IL-3R and CSF-1R. We will use 2D-gel electrophoresis, immuno-precipitation methods and massspectrometry to elucidate the molecular partners of Tec in cells and define the important Tec substrates in cell signalling. This project involves a wide range of biochemical techniques as well as cell culture methods.
Structure-based Drug Design
We have used the 3-dimensional structure of the Tec SH3 domain as a target for structure-based drug design. The initial design incorporates 3 components, one of which has been shown to bind to the domain at the predicted site. This project is a collaboration with Dr Simon Pyke (School of Chemistry and Physics) and involves a range of approaches and would suit those with a strong interest in computing, chemistry or molecular interactions.
- Chemical synthesis and testing of the other components of the initial design
- Optimisation of the initial "hit" to enhance ligand affinity and selectivity
- Testing the ligands for agonist/antagonist activity
- Dynamic combinatorial library screening approaches
1. Model of a small molecule ligand bound to the TecSH3 domain.
Chemical shift changes induced upon ligand binding are shown on the ribbon structure.