Structural and Chemical biology of protein phosphatases and signalling proteins
Reversible phosphorylation of proteins is the main regulatory mechanism in signal transduction pathways. Triggered by external stimuli, the balance between the activities of protein kinases and protein phosphatases controls diverse cellular processes, like cell proliferation and differentiation, neoplasic transformation, cell adhesion and metabolism. Alteration in the expression profiles, catalytic activities and 3-dimensional structures of protein kinases and phosphatases are responsible for a large number of decimating diseases (diabetes, cancer, neuropathies), which are still difficult to treat.
The main focus of our research is to elucidate the molecular basis for macromolecular recognition and specificity in signalling events. Using X-ray crystallography and other biophysical and biochemical methods, we study the interaction of signalling protein (phosphatases, kinases) with their biological targets and ligands.
Signalling pathways, and in particular phosphatases, are key players in many human diseases and essential virulence factors in pathogenesis. An important part of our research is now focused on the chemical intervention of such targets through different programmes of drug discovery and structure-based drug design. In vitro screening and computational design are combined with cell validation of inhibitors and then translated to relevant animal models in collaboration with laboratories across Europe and US.