Protein Science and Structural Biology
My group focuses on structures and host cell interactions of emerging viruses.
We study how viruses belonging to viral families Arenaviridae and Bunyaviridae infect their host cells. Many of these viruses are pathogens causing serious diseases. These include Lassa virus, Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus and many hantaviruses. Despite the medical relevance of arena- and bunyaviruses, very little is known about their detailed three-dimensional structures and infection mechanisms. We use mainly electron cryo-microscopy, combined with computational 3D reconstruction methods, to solve the structures of mature virions, and intermediate structures existing during entry, membrane fusion and maturation.
The infection of a host cell by a virus is a complicated process and its study requires a combination of different techniques and model systems. Our electron cryo-microscopy and tomography studies will be combined with other complementary imaging and biophysical techniques to yield a detailed description of viral infection. For example, we are combining electron tomography of infected cells with light microscopy of GFP-labeled particles and tomographic subvolume averaging techniques and high-resolution single particle electron cryo-microscopy with fitting of X-ray structures of viral glycoproteins into density maps of whole virus particles.
The work is carried out in the bio-safety containment laboratory of Oxford Particle Imaging Centre, which provides facilities for virus production and high resolution electron cryo-microscopy and tomography.