With over 560 proteases in the human body, proteolysis affects the fate of every protein. Proteolysis results in either protein degradation, leading to protein removal and breakdown into amino acids, or fine and specific proteolytic processing that produces stable, precisely modified protein chains. Processed proteins often have altered activity, protein interactions, structure, or cellular localization and hence are implicated in many human diseases.
Many proteases have been identified and some are associated with disease states or have been shown to play key roles in normal cellular development, metabolism and maintenance. Even so, our knowledge of protease biology is far from complete: the substrate repertoires of most proteases are poorly annotated and the factors that dictate protease cleavage specificity are not fully understood.
We are using cutting-edge proteomics methods combined with cell biology, biochemistry and bioinformatics methods in order to:
- Study substrate selectivity and specificity of different proteases from different protease classes.
- Characterize the substrate repertoires and the biological impact of mitochondrial rhomboid and of calcium-dependent calpain proteases.
- Develop novel proteomic methods to study different aspects of the ubiquitin-proteasome system.