Special Lecture

Structural Virology: a personal history

Prof. Michael G. Rossmann

I will describe my gradually evolving role as a scientist from my birth in Frankfurt (Germany) to my education in Britain, my post-doc years and my experiences as an independent investigator at Purdue University. I had my first encounter with an electronic computer while I was a post-doc in the laboratory of William Lipscomb at the University of Minnesota. Subsequently I participated in the first three dimensional structure determinations of proteins while working in Max Perutz’s laboratory in Cambridge, England. After six years back in England my family moved to Indiana (USA) where my home remains till to-day. At Purdue University I first studied the structure of enzymes and in the process I discovered the nucleotide binding domain present in most proteins that use ATP, NAD and other nucleotides as a cofactor. I also recognized the evolution of complex protein structures from conserved domains with specific functions. With this success I started what had been on my mind already for a long time, namely the structural analyses of viruses. Initially I studied plant viruses but then progressed to investigating small RNA animal viruses. We discovered that some plant and animal RNA viruses have closely similar structures and therefore presumably had a common evolutionary origin. Next I became interested in somewhat larger alpha and flavi viruses (e.g. dengue and yellow fever) that had lipid membrane envelopes. In turn that has led to the study of very large dsDNA viruses as big as small bacteria as well as studies of bacterial viruses that require complex molecular motors for different parts of their life cycle. While developing crystallographic techniques for the study of viruses it has become progressively more apparent that electron microscopy is an important new tool. I helped to show how to usefully combine crystallographic analyses of viral components with electron microscopy of whole viruses or virus-substrate complexes. However, with the development of new electron detectors it seems likely that electron microscopy might soon at least partially eclipse X-ray crystallography.