Research Overview
The research in our laboratory is focused on structural biology with an ultimate thrust to uncover molecular details of cellular signaling events and to use this information as a rational base for drug design efforts. In particular, studying integral membrane proteins and cross-membrane signal transduction is of key importance: despite the fact that they represent targets for the majority of drug leads and recent explosive advances in structural biology, the number of membrane protein structures solved each year falls far behind the one of soluble proteins and our understanding of the signal transduction across the membrane is still limited. We choose integrins as a model system for methods development and applied acquired expertise to other cell surface receptors
and their downstream cytoplasmic targets. We have determined several structures of the key players (and their complexes) in integrin and other signaling pathway by macromolecular NMR (16 have been deposited to the PDB). We routinely use ITC to define thermodynamic parameters of protein-protein interactions. We have also optimized membrane-mimicking system, the nanodiscs, for more efficient application of solution NMR methods to study integral membrane proteins in the most natural environment with the goal to elucidate molecular details of the across-membrane signal transduction mechanisms.
