Dr. Gerhard Wagner was the first to receive a college education in his family. Born to a blue-collar family, after WWII in the German-speaking part of Czechoslovakia, his family was forced to leave and ended up in Southern Bavaria where he grew up. Due to his school records he could go to a humanistic gymnasium, an institution that teaches classical antiquity specifically, and received an education with nine years of Latin and six years of classical Greek but also a good education in math and some physics. There, he had an excellent math/physics teacher and became fascinated with physics.

After graduation Dr. Wagner was drafted to German military service for 18 months. He studied physics at the Technical University of Munich. With his good grades, he received a fellowship from the Studienstiftung des Deutschen Volkes. Meetings with his fellowship advisors made him aware of the field of biophysics and he looked into doing something in that direction. Thus, for his Diploma thesis, he built a Mössbauer spectrometer and recorded 57Fe of hemoglobins, myoglobins and ferredoxins. From the temperature dependence of the quadrupolar splitting of 57Fe he could calculate the optical spectrum of hemoglobin including the Soret band.

However, Mössbauer spectroscopy is very insensitive, and one can measure a single parameter, the quadrupolar splitting, and its temperature dependence. At that time, Dr. Wagner’s diploma advisor went for a sabbatical at Bell labs (1972) where he learned about NMR spectroscopy from Robert Shulman. He communicated to Dr. Wagner that NMR spectra have many lines, compared to two in a Mössbauer spectrum. The Shulman lab had just discovered the paramagnetically shifted heme resonances of hemoglobin. Thus, he concluded this must be more interesting. The person who had discovered the heme resonances in the Shulman lab, Kurt Wüthrich, had just moved to the ETH Zürich. Thus he decided to pursue a Ph.D. in his lab and moved to Zürich beginning of 1973 although some of his Munich advisors told him that “everything has been done in NMR already.”

In Zürich he started to work with a small rigid protein, the basic pancreatic trypsin inhibitor, BPTI, for which the lab of Robert Huber in the Max-Planck Institute in Munich had just determined the highest resolution X-ray structure at 1.0 Å. Studying the temperature dependence of BPTI’s NMR spectrum he discovered that aromatic side chains undergo rapid 180 degree flips, and he could accelerate or slow down flip rates with temperature variation. This suggested spatial rearrangements of more than 1.7 Å and was entirely contradictory the view of protein structures at that time but changed the way structural biologists think about dynamic proteins now.

After graduation, he spent six months at the Chemistry department of MIT to explore solid state NMR. Afterwards he went back to the Wüthrich lab in Zürich to continue work on solution NMR of proteins. He learned about the nuclear Overhauser effect (nOe) and developed procedures for sequence specific resonance assignments of proteins. He was the first to completely assign the resonances of an entire protein (BPTI). This became the foundation of solving protein structures in solution by NMR. The first structure he determined was for rabbit metallothioneine 2. When he and his team were ready to publish it a crystal structure was reported for the same protein but was entirely different from his topology. After intensive scrutiny of his data it became clear that his structure was correct, and the crystal structure was not. This made the crystallographers aware of him, and he received offers for faculty positions at Duke, the University of Michigan, and the University of Minnesota. He accepted the position in Ann Arbor where he was hired as Associate Professor with tenure in 1987.

Already before his arrival in Michigan, he had ordered construction of a triple resonance probe for his new spectrometer. This allowed pulsing 1H, 15N and 13C. After the probe was delivered in 1988, he developed triple resonance methods for conformation-independent sequential assignments of proteins. This has become the basis for today’s resonance assignments of proteins and structure determination of proteins in solution up to 50 kDa and above. Due to this achievement, Dr. Wagner obtained an offer from Harvard Medical School where he has stayed since 1990.

At Harvard he has determined numerous structures (>50) of important proteins, primarily in the field of translation initiation, apoptosis and T-cell biology. He and his team have discovered small molecule inhibitors of protein-protein interactions and found some to have tumor suppressive activities. He believes that these can become powerful anti-cancer agents.

On the other hand, he has become excited by the structural and functional studies of integral membrane proteins. To this end, he and his team have developed a technology to place membrane proteins into covalently circularized phospholipid nanodiscs. Dr. Wagner can make nanodiscs of various size from 9 nm to 80 nm and place membrane proteins inside to be studied with NMR and electron microscopy. This includes whole GPCRs with associated G proteins, the whole T-cell receptor CD3 complex or an entire poliovirus injecting its RNA through the nanodisc. This is the most exciting recent achievement in Dr. Wagner’s lab.

Website: gwagner.med.harvard.edu