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
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.
