The Pfuhl Group
The main focus of the group is to understand the functional mechanisms of proteins involved in regulatory processes in the heart and other muscles as well as those involved in the regulation of kinases. In the heart muscle we investigate the structure, interactions and dynamics of the thick filament protein Myosin Binding Protein C. Mutations in the gene for this protein are one of the leading causes of cardiomyopathies. A more general role is played by the cardiac stress response protein MS1/STARS which is quickly upregulated under conditions of hypoxia and we try to find out how it operates. We also study proteins fund in other types of muscle, such as calponin, an important regulator of smooth muscle contraction.
A second major interest is the regulation of kinase function by regulatory domains or accessory and adapter proteins. The main focus in this area is the characterisation of the very unusual leucine zipper in the regulatory domain of the cell cycle regulated Nek2 kinase.
The major motivation for studying this diverse set of proteins comes from their involvement in a range of diseases such as cardiomyopathies and cancer. A detailed understanding of structure and function of medically important proteins will in the long term stimulate and contribute to the development of new and improved therapies.
The methods we use involve both functional as well as structural methods. Functional assays are mainly looking and protein-protein interaction using e.g. cosedimentation, isothermal titration calorimetry and fluorescence. Structural methods involve mainly solution and solid state NMR spectroscopy as well as circular dichroism and molecular modelling.
- Mathias Gautel (KCL) Myosin Binding Protein C
- Mohammed El-Mezgueldi (University of Leicester) Calponin
- Richard Bayliss (ICR) TACC3/chTOG/MSPS
- Andrew Fry (University of Leicester) Nek2 kinase
- Steven Brown (Warwick University) solid state NMR of F-actin complexes
The research is funded by the British Heart Foundation.