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.

1. Chemical synthesis and testing of the other components of the initial design
2. Optimisation of the initial "hit" to enhance ligand affinity and selectivity
3. Testing the ligands for agonist/antagonist activity
4. Dynamic combinatorial library screening approaches

Figure 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.