Enveloped viruses and coated vesicles - electron cryo-microscopy and tomography
We study the structure and the molecular assembly mechanisms of important, pathogenic, enveloped viruses (e.g. HIV and Influenza virus), and of cellular trafficking vesicles (e.g. clathrin and COPI coated vesicles). Viruses and vesicles are extraordinary self-assembling machines – the protein building blocks interact with one another to bring all the components or cargo together, to reshape the lipid bilayer, and to release a free virus or vesicle. The building blocks will often then undergo an intricate reassembly to prepare for fusion with a target cell or membrane. The level of understanding we aim to achieve could be imagined as a 3D, functionally annotated movie, with molecular resolution, showing the assembly and budding process.
To reach this goal we need to obtain detailed structural information at different stages during assembly, ideally under close-to-native conditions, even within cells. This is a challenge for conventional structural biology tools, so we are also developing and applying new approaches for electron cryo-microscopy and tomography, correlated fluorescence and electron microscopy, and image processing.