School of Biosciences

Research Overview

Mechanism and Concepts of Protein Quality Control

Nature has evolved efficient mechanisms of quality control to ensure that all proteins are biologically active, localised to the proper cellular compartment and present in appropriate quantity. The failure of quality control can influence cell growth and can cause severe diseases that are based on protein folding, localisation and degradation problems. In this context, we study the evolutionarily conserved family of HtrA proteases that are involved in detection of misfolded proteins, signal recognition and integration into unfolded protein response pathways as well as regeneration of the functional state. Of particular interest are the implications of HtrAs in bacterial stress response, Alzheimer's disease and cancer.

Target Directed Proteolysis

To establish the use of proteases as a tool in vivo we developed a new method, Target Directed Proteolysis (TDP). TDP uses Tobacco Etch Virus NIa (TEV) protease, which recognises a seven amino acid consensus sequence that is asymmetrically cleaved. Because of its distinct specificity, TEV protease can be expressed in cellular compartments without interfering with viability. Polypeptides that are not natural substrates of TEV protease are proteolysed if they carry the appropriate cleavage site. This method is applied to conditionally inactivate essential proteins and to study their structure, function and translocation.

Research Group

Molecular Cell Biology