|Fig 1.Unstained Rift Valley fever virus (RVFV) particles embedded in vitreous ice, and imaged with an field emission gun electron microscope|
|Fig 2. Three dimensional reconstruction of RVFV calculated by combining data from several projection images (Fig 1) reveals the glycoprotein organization|
My group focuses on structures and host cell interactions of emerging viruses.
We study how viruses belonging to 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 electron cryomicroscopy, combined with computational 3D reconstruction methods, to solve the structures of mature virions, in addition to 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 cryomicroscopy and tomography studies are combined with complementary imaging and biophysical techniques to yield a detailed description of viral infection. For example, we are combining tomographic subvolume averaging techniques and high-resolution single particle electron cryomicroscopy with fitting of X-ray structures of viral glycoproteins into density maps of whole virus particles. Our group is also active in developing computational methods for these tasks.
The work is carried out at the Division of Structural Biology (StruBi) and Oxford Particle Imaging Centre (OPIC), which offers a high bio-safety containment laboratory providing facilities for virus production and high resolution electron cryomicroscopy and tomography.
Assembly of complex viruses exemplified by a halophilic euryarchaeal virus
De Colibus L. et al, (2019), Nature Communications, 10
The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K
Bushell SR. et al, (2019), Nature Communications, 10
Assessment of Immunogenicity and Efficacy of a Zika Vaccine Using Modified Vaccinia Ankara Virus as Carriers.
López-Camacho C. et al, (2019), Pathogens (Basel, Switzerland), 8
Multiple liquid crystalline geometries of highly compacted nucleic acid in a dsRNA virus.
Ilca SL. et al, (2019), Nature
Understanding the structure and role of DNA-PK in NHEJ: How X-ray diffraction and cryo-EM contribute in complementary ways.
Wu Q. et al, (2019), Prog Biophys Mol Biol