David Cowburn's research centers on the application of structural biology, and particularly, nuclear magnetic resonance (NMR), to biological problems. He attempts to develop and apply useful new methods to challenging problems not readily addressed by standard methods. His work is frequently collaborative. Some significant structural contributions include the first SH2 domain, the first proapoptopic BCL family member, high affinity complexes of specific SH3/ligands and stapled peptides/targets, and pleckstrin homology domain/PIP interactions. Methodological contributions cover new isotopic labeling methods, especially segmental labeling by expressed protein ligation, and production of kinases for NMR analysis; analysis of relaxation properties for weak self association, motion of dual domains, contribution of CSA; in-cell NMR with advanced expression methods; mimics of protein-protein interactions, and molecular dynamics and NMR simulation methods. Using NMR, there is a strong effort to understand how intrinsically disordered systems can have significant functions roles in the nuclear pore. This project involves also scattering techniques and extensive simulation to probe kinetic properties. A significant area of focus is the structural biology of protein domains in intracellular signal transduction, including SH2, SH3, kinase, phosphatase, PH domains, and many others and how natural ligands interact with them. Signaling disorders related to these domains lead to many disease states.
