Most proteins are complex molecules. In the late 1970s, working with them was complicated and expensive. “We were able to work with only a very few proteins, as analysing them required huge quantities of each one in a highly pure form,” the ETH professor explains. Back then, working with DNA would have been more attractive, because it was possible to make more progress faster than working with proteins. But his doctoral advisor, biochemist Dietmar Braun from Ciba-Geigy, continued to pursue protein research and built up a group devoted to the topic at the pharmaceutical company.
“Ciba-Geigy had a strong protein chemical group that I was able to join even while I was still working on my master’s degree,” Aebersold recalls. The company had laboratory facilities that the Biozentrum didn’t. “There I was able to acquire skills in this niche that turned out to be very useful later on,” Aebersold says.
As a doctoral student, he had a book that contained all the known sequences of amino acids in proteins. It was a slim volume. Aebersold still has it today: “This book motivated me to refine techniques that we could use to determine amino acid sequences in proteins more easily than before.”
Diving into creative chaos
The laboratory that allowed him to do this was Lee Hood’s lab at Caltech in the United States. It was in the vanguard of laboratory automation and the development of analysis equipment. Aebersold remembers the special atmosphere Hood created: “It was creative chaos.” During his time in the lab, Aebersold collaborated with chemists and engineers to construct his first protein sequencing machine, which could automatically carry out the Edman degradation, a complicated chemical process.
After finishing his postdoc assignment, Ruedi Aebersold moved his wife and their three children to the University of British Columbia in Vancouver, where he was able to set up his first group as an assistant professor in the 1980s.
Mass spectrometry was undergoing a rapid transformation at this time. Another researcher, John Fenn, had just invented electrospray ionisation. This made it possible for the first time to ionise large, fragile molecules like proteins – in other words, giving them an electrical charge and transferring them into the vacuum system of a mass spectrometer. This meant scientists could determine the mass of these molecules and even their amino acid sequence in the mass spectrometer.
Aebersold procured a spectrometer and used it to analyse proteins, thus laying the foundation for his further work. “By coincidence, my education in protein biochemistry had put me in the perfect position to generate biologically relevant data and not just chemical/analytical data,” he says.