McDonald lab Signalling and Structural Biology Laboratory

This figure shows the scales that we work with in the lab

We study enzymes called protein kinases to understand how they operate within networks that drive biological decision-making processes such as cell differentiation, cell patterning and cell fate. 

We use molecular approaches to visualise the three-dimensional structure of assemblies of two related groups of protein kinases; receptor tyrosine kinases that face both outside and inside of the cell and membrane-associated serine/threonine kinases. Once activated, protein kinases add labels to their cellular targets to initiate, amplify or pass on messages within cells. They play critically important and complex roles in human physiology and diseases such as cancer. 
My lab applies research techniques collectively referred to as structural biology. These methods include X-ray crystallography, cryo-electron microscopy and small angle X-ray scattering. Together they can be used to map the position of all atoms in the proteins we study allowing us to define their shape and molecular function. 
We combine structural biology research with biochemical and cell-based experiments to establish that the mechanisms we work out in test tubes also apply to living cultured cells. We are also using our structural information to develop biological and chemical tools able to switch ‘on’ or ‘off’ our protein kinase targets. In some cases, these tools can help patients by providing a starting point for developing drugs that can be taken into clinical trials.