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Stephen Harrison has made important contributions to structural biology, most notably by determining and analyzing the structures of viruses and viral proteins, by crystallographic analysis of protein/DNA complexes, and by structural studies of protein-kinase switching mechanisms. The initiator of high-resolution virus crystallography, he has moved from his early work on tomato bushy stunt virus ( to the study of more complex human pathogens, including the capsid of human papillomavirus, the envelope of dengue virus, and several components of HIV. He has also turned some his research attention to even more complex assemblies, such as clathrin coated vesicles.
Recently the Harrison Laboratory has been studying the structures of viral proteins that mediate entry into cells. These investigations reveal fundamental properties not only of viruses but also of their host cells. The laboratory's current focus is on the study of double-stranded RNA viruses to help determine how nonenveloped viruses (viruses without lipid membranes of their own) enter cells. The structures of entry proteins from reovirus and rotavirus suggest that major conformational rearrangements in the protein oligomers may drive membrane penetration steps. Eludidating the mechanisms of viral entry may reveal targets for antiviral drugs.
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