2018 Laukien Prize Winner Announcement

The Gunther Laukien Prize is awarded annually at the Experimental NMR Conference (ENC) to recognize cutting-edge NMR research.

The Wagner Lab focuses research on structural aspects of protein function, studying how proteins interact with macromolecules or small molecule ligands and those interactions relate to biological function. 

Currently Professor Wagner is interested in understanding mechanisms of human translation initiation, transcriptional activation mediated by activator co-activator interactions, T-cell activation, non-ribosomal peptide synthesis and membrane protein structure. He has determined more than 50 unique structures of proteins in solution. A major effort is focused on the discovery and characterization of small molecule inhibitors of protein-protein interactions that might have therapeutic use in curing human disease. 

In addition to biological research, Professor Wagner continues to be strongly interested in the further development of NMR methods. This includes procedures for advanced sampling and data reconstruction. Another recent focus is on exploiting the TROSY effect while detecting low-g nuclei in solution NMR spectroscopy. 

Biography

Gerhard Wagner was born in 1945 in Bor, Czech Republic and grew up in Southern Bavaria. During his undergraduate years he studied physics at the Technische Universität of Munich, graduating in 1972 with a Diploma thesis on Mössbauer spectroscopy of iron containing proteins. He then pursued a Ph.D. at the ETH Zurich under the guidance of Professor Kurt Wüthrich. His initial effort was to understand the NMR spectrum of the basic pancreatic trypsin inhibitor, BPTI. 

His initial efforts were directed at understanding the phenomenon of amide hydrogen/deuterium exchange as a tool to understand protein breathing dynamics with residue specific resolution. However, this required sequence specific resonance assignments, which were not yet available. Thus, he focused on the resonances of the aromatic side chains and discovered that aromatic rings flip rapidly even in the most rigid proteins. The rates of these processes and their temperature and pressure dependence can be measured quantitatively by NMR. Importantly, Wagner's data provided an initial test bed for the development of molecular dynamics calculations. In a parallel effort, he studied protein dynamics with hydrogen-deuterium exchange at limits of uncorrelated (EX2) and correlated (EX1) exchange. Quantitative analysis of exchange rates indicated that exchange of the innermost amides required complete unfolding of BPTI. In 1977 he obtained his Ph.D. with a thesis on NMR studies of protein dynamics. 

Subsequently, Gerhard joined the group of Professor John Waugh at MIT for a postdoctoral stay to explore the potential of solid state NMR for protein studies. In 1979 he returned to the ETH and established a technology for sequential resonance assignments based on 1D NOE and spin decoupling, which allowed assignment of all slowly exchanging amides in the b-sheet secondary structures of BPTI. With the introduction of 2D NMR methods he quickly assigned the entire spectrum of BPTI, which was the first complete NMR assignment for any protein. 

The technology he developed formed the basis for the first solution NMR structures of proteins. In 1986, prior to moving to the University of Michigan, Wagner initiated construction of a triple resonance probe to enable precise measurements of homonuclear couplings by observing HN-Ca cross peaks without flipping the Ha between evolution and detection periods. He discovered this possibility when measuring Ha-Hb cross peaks of 113Cd-bound cysteines in the protein metallothionein. In addition, in 1988, when executing the experiment with G. Montelione on a small 15N labeled peptide and natural abundance 13C, he discovered sequential cross peaks connecting amides with the Ca of the preceding residues. This was essentially the first HNCA type experiment, and a feature now used extensively in triple-resonance assignments of proteins. 

Professor Wagner has been at Harvard Medical School since 1990. In addition, he has organized numerous symposia and is currently on the editorial board of several prestigious publications including the Journal of Magnetic Resonance and Journal of Biomolecular NMR.